TY - JOUR T1 - Contributions of the C-terminal domain to the control of P2X receptor desensitization. AN - 69381714; 10608821 AB - The P2X purinergic receptor channels (P2XRs) differ among themselves with respect to the rates of desensitization during prolonged agonist stimulation. Here we studied the desensitization of recombinant channels by monitoring the changes in intracellular free Ca(2+) concentration in cells stimulated with ATP, the native and common agonist for all P2XRs. The focus in our investigations was on the relevance of the P2XR C terminus in controlling receptor desensitization. When expressed in GT1 cells, the P2XRs desensitized with rates characteristic to each receptor subtype: P2X(1)R = P2X(3)R > P2X(2b)R > P2X(4)R > P2X(2a)R > P2X(7)R. A slow desensitizing pattern of P2X(2a)R was mimicked partially by P2X(3)R and fully by P2X(4)R when the six-amino acid sequences of these channels located in the cytoplasmic C terminus were substituted with the corresponding arginine 371 to proline 376 sequence of P2X(2a)R. Changing the total net charge in the six amino acids of P2X(4)R to a more positive direction also slowed the receptor desensitization. On the other hand, substitution of arginine 371-proline 376 sequence of P2X(2a)R with the corresponding sequences of P2X(1)R, P2X(3)R, and P2X(4)R increased the rate of receptor desensitization. Furthermore, heterologous polymerization of wild-type P2X(2a)R and mutant P2X(3)R having the C-terminal six amino acids of P2X(2a)R at its analogous position resulted in a functional channel whose desensitization was significantly delayed. These results suggest that composition of the C-terminal six-amino acid sequence and its electrostatic force influence the rate of receptor desensitization. JF - The Journal of biological chemistry AU - Koshimizu, T AU - Koshimizu, M AU - Stojilkovic, S S AD - Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12/31/ PY - 1999 DA - 1999 Dec 31 SP - 37651 EP - 37657 VL - 274 IS - 53 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Receptors, Purinergic P2 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Cell Line KW - Calcium Signaling KW - Receptors, Purinergic P2 -- genetics KW - Receptors, Purinergic P2 -- metabolism KW - Receptors, Purinergic P2 -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69381714?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Contributions+of+the+C-terminal+domain+to+the+control+of+P2X+receptor+desensitization.&rft.au=Koshimizu%2C+T%3BKoshimizu%2C+M%3BStojilkovic%2C+S+S&rft.aulast=Koshimizu&rft.aufirst=T&rft.date=1999-12-31&rft.volume=274&rft.issue=53&rft.spage=37651&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-08 N1 - Date created - 2000-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chlamydial homologues of the MACPF (MAC/perforin) domain AN - 17488241; 4684862 AB - Chlamydiae are major human pathogens and the etiological agents of several diseases in humans, other mammals and birds. Depending on the serotype, infection with Chlamydiae trachomatis can result in trachoma, sexually-transmitted diseases or inclusion conjunctivitis. A second chlamydial species, C. pneumoniae, is associated with upper respiratory tract infections. Following internalisation by eukaryotic cells, chlamydiae are enveloped within membrane-bound compartments, or inclusions, that do not fuse with lysosomes. Multiple chlamydiae in a eukaryotic cell fuse their inclusions into a single large inclusion that contains the infectious but metabolically-inactive elementary body (EB). EBs differentiate into replicative, reticulate bodies (RBs) 6-8 hours postinfection. RBs eventually revert to EBs and are released from the host cell to continue the infectious process. The complete genome sequences of C. trachomatis and C. pneumoniae have been recently determined. After the predicted protein sequences of C. trachomatis were deposited in the database, the web-based annotation resource database SMART (http://coot.emblheidelberg.de/SMART/) automatically predicted that the C. trachomatis hypothetical protein CT153 contains a MACPF domain. This domain is present in mammalian membrane-attack complex and perforin proteins, but had not been previously identified in non-eukaryotic proteins. The associated statistical significance of this prediction (E = 7.5 x 10 super(-3)) was corroborated using PSI-BLAST database searches with an E-value inclusion threshold of 0.001. For example, two rounds of a PSI-BLAST search using the human complement component 9 MACPF domain sequence (amino acid residues 138-503) as the query resulted in identification of the C. trachomatis CT153 protein as significantly similar to this domain with an E-value of 3 x 10 super(-7). JF - Current Biology AU - Ponting, C P AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20814, USA, Ponting@ncbi.nlm.nih.gov Y1 - 1999/12/30/ PY - 1999 DA - 1999 Dec 30 SP - 1 VL - 9 IS - 24 SN - 0960-9822, 0960-9822 KW - domains KW - homologs KW - CT153 protein KW - MACPF protein KW - Microbiology Abstracts B: Bacteriology KW - Chlamydia trachomatis KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17488241?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Biology&rft.atitle=Chlamydial+homologues+of+the+MACPF+%28MAC%2Fperforin%29+domain&rft.au=Ponting%2C+C+P&rft.aulast=Ponting&rft.aufirst=C&rft.date=1999-12-30&rft.volume=9&rft.issue=24&rft.spage=R913&rft.isbn=&rft.btitle=&rft.title=Current+Biology&rft.issn=09609822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis ER - TY - JOUR T1 - Differential localization of protein kinase C delta by phorbol esters and related compounds using a fusion protein with green fluorescent protein. AN - 69370486; 10601287 AB - Enzyme localization often plays a controlling role in determining its activity and specificity. Protein kinase C (PKC) has long been known to translocate in response to physiological stimuli as well as to exogenous ligands such as the phorbol esters. We report here that different phorbol derivatives and related ligands, selected for differences in chemical structure and profile of biological activity, induce distinct patterns of redistribution of PKC delta. Localization of a PKC delta-green fluorescent protein (GFP) fusion construct was monitored in living Chinese hamster ovary cells as a function of ligand, concentration, and time using confocal laser scanning microscopy. delta-PKC-GFP was expressed predominantly in the cytoplasm, with some in the nucleus and perinuclear region. Phorbol 12-myristate 13-acetate (PMA) induced plasma membrane translocation followed by slower nuclear membrane translocation. As the concentration of PMA increased, the proportion of nuclear to plasma membrane localization increased markedly. In contrast to PMA, bryostatin 1, a unique activator of PKC that induces a subset of PMA-mediated responses while antagonizing others, at all doses induced almost exclusively nuclear membrane translocation. Like PMA, the complete tumor promoter 12-deoxyphorbol 13-tetradecanoate induced plasma membrane and slower nuclear membrane translocation, whereas the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate, which differs only in its side chain, induced a distinctive distribution of PKC delta-GFP. Finally, the novel constrained diacylglycerol derivative B8-DL-B8 induced a slow Golgi localization. We speculate that differential control of PKC delta localization may provide an interesting strategy for producing ligands with differential biological consequences. JF - The Journal of biological chemistry AU - Wang, Q J AU - Bhattacharyya, D AU - Garfield, S AU - Nacro, K AU - Marquez, V E AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12/24/ PY - 1999 DA - 1999 Dec 24 SP - 37233 EP - 37239 VL - 274 IS - 52 SN - 0021-9258, 0021-9258 KW - Bryostatins KW - 0 KW - Diglycerides KW - Isoenzymes KW - Lactones KW - Luminescent Proteins KW - Macrolides KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - bryostatin 1 KW - 37O2X55Y9E KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Recombinant Fusion Proteins -- analysis KW - Animals KW - Diglycerides -- pharmacology KW - Transfection KW - Dose-Response Relationship, Drug KW - CHO Cells KW - Lactones -- pharmacology KW - Cricetinae KW - Protein Kinase C -- analysis KW - Isoenzymes -- analysis KW - Luminescent Proteins -- analysis KW - Tetradecanoylphorbol Acetate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69370486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Differential+localization+of+protein+kinase+C+delta+by+phorbol+esters+and+related+compounds+using+a+fusion+protein+with+green+fluorescent+protein.&rft.au=Wang%2C+Q+J%3BBhattacharyya%2C+D%3BGarfield%2C+S%3BNacro%2C+K%3BMarquez%2C+V+E%3BBlumberg%2C+P+M&rft.aulast=Wang&rft.aufirst=Q&rft.date=1999-12-24&rft.volume=274&rft.issue=52&rft.spage=37233&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-13 N1 - Date created - 2000-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional activation of the human manganese superoxide dismutase gene mediated by tetradecanoylphorbol acetate. AN - 69366185; 10601319 AB - Transcriptional activation of human manganese superoxide dismutase (MnSOD) mRNA induced by a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), was examined to identify the responsive transcriptional regulator. The effect of various deletions and mutations within the 5'-flanking region of the human MnSOD gene promoter was evaluated using the luciferase reporter system in A549 human lung carcinoma cells. Deletion of a region between -1292 and -1202 nucleotides upstream of the transcription start site abolished TPA-responsive induction, whereas deletion of the putative binding sequence for NF-kappaB or AP-1 did not. The region between -1292 and -1202 contains a cAMP-responsive element-like sequence, TGACGTCT, which we identified as the manganese superoxide dismutase TPA-responsive element, MSTRE. Site-specific mutation of the MSTRE abolished the TPA-responsive induction, validating the critical role of this sequence. We detected specific MSTRE activity from nuclear extracts and demonstrated by antibody supershift assay that this activity is closely related to CREB-1/ATF-1. TPA treatment rapidly induced phosphorylation of the CREB-1/ATF-1-like factor via the protein kinase C pathway. These results led us to conclude that the human MnSOD gene having the promoter construct used in this study is induced by TPA via activation of a CREB-1/ATF-1-like factor and not via either NF-kappaB or AP-1. In addition, we found that this induction was blocked by inhibitors of flavoproteins and NADPH oxidases, indicating involvement of enhanced generation of superoxide radical anion as an upstream signal. JF - The Journal of biological chemistry AU - Kim, H P AU - Roe, J H AU - Chock, P B AU - Yim, M B AD - Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-0342, USA. Y1 - 1999/12/24/ PY - 1999 DA - 1999 Dec 24 SP - 37455 EP - 37460 VL - 274 IS - 52 SN - 0021-9258, 0021-9258 KW - Activating Transcription Factor 1 KW - 0 KW - CREB1 protein, human KW - Cyclic AMP Response Element-Binding Protein KW - DNA-Binding Proteins KW - Transcription Factors KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - NADPH Oxidase KW - EC 1.6.3.1 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Transcription Factors -- physiology KW - Promoter Regions, Genetic KW - Base Sequence KW - Tumor Cells, Cultured KW - Phosphorylation KW - NADPH Oxidase -- antagonists & inhibitors KW - Humans KW - Molecular Sequence Data KW - Response Elements KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Superoxide Dismutase -- genetics KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69366185?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Transcriptional+activation+of+the+human+manganese+superoxide+dismutase+gene+mediated+by+tetradecanoylphorbol+acetate.&rft.au=Kim%2C+H+P%3BRoe%2C+J+H%3BChock%2C+P+B%3BYim%2C+M+B&rft.aulast=Kim&rft.aufirst=H&rft.date=1999-12-24&rft.volume=274&rft.issue=52&rft.spage=37455&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-13 N1 - Date created - 2000-01-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF059197; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes. AN - 69381096; 10611318 AB - Genetic inactivation of the transforming growth factor-beta (TGF-beta) signaling pathway can accelerate tumor progression in the mouse epidermal model of multistage carcinogenesis. By using an in vitro model of keratinocyte transformation that parallels in vivo malignant conversion to squamous cell carcinoma, we show that v-ras(Ha) transduced primary TGF-beta1-/- keratinocytes and keratinocytes expressing a TGF-beta type II dominant-negative receptor transgene have significantly higher frequencies of spontaneous transformation than control genotypes. Malignant transformation in the TGF-beta1-/- keratinocytes is preceded by aneuploidy and accumulation of chromosomal aberrations. Similarly, transient inactivation of TGF-beta signaling with a type II dominant-negative receptor adenovirus causes rapid changes in ploidy. Exogenous TGF-beta1 can suppress aneuploidy, chromosome breaks, and malignant transformation of the TGF-beta1-/- keratinocytes at concentrations that do not significantly arrest cell proliferation. These results point to genomic instability as a mechanism by which defects in TGF-beta signaling could accelerate tumor progression in mouse multistage carcinogenesis. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Glick, A AU - Popescu, N AU - Alexander, V AU - Ueno, H AU - Bottinger, E AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. glicka@dc37.nci.nih.gov Y1 - 1999/12/21/ PY - 1999 DA - 1999 Dec 21 SP - 14949 EP - 14954 VL - 96 IS - 26 SN - 0027-8424, 0027-8424 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Receptors, Transforming Growth Factor beta -- genetics KW - Animals KW - Mice, Mutant Strains KW - Carcinoma, Squamous Cell -- etiology KW - Dose-Response Relationship, Drug KW - Transduction, Genetic KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Drug Resistance KW - Mice KW - Calcium -- pharmacology KW - Signal Transduction KW - Genes, ras KW - Transforming Growth Factor beta -- pharmacology KW - Aneuploidy KW - Keratinocytes -- pathology KW - Transforming Growth Factor beta -- genetics KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69381096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Defects+in+transforming+growth+factor-beta+signaling+cooperate+with+a+Ras+oncogene+to+cause+rapid+aneuploidy+and+malignant+transformation+of+mouse+keratinocytes.&rft.au=Glick%2C+A%3BPopescu%2C+N%3BAlexander%2C+V%3BUeno%2C+H%3BBottinger%2C+E%3BYuspa%2C+S+H&rft.aulast=Glick&rft.aufirst=A&rft.date=1999-12-21&rft.volume=96&rft.issue=26&rft.spage=14949&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-27 N1 - Date created - 2000-01-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cell Growth Differ. 1992 May;3(5):291-8 [1633111] Science. 1996 Jan 19;271(5247):350-3 [8553070] Cell. 1992 Nov 13;71(4):587-97 [1423616] Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):770-4 [8421714] J Immunol Methods. 1993 Jan 14;158(1):17-25 [8429213] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6076-80 [7687059] J Virol. 1994 Feb;68(2):933-40 [7507187] Cancer Genet Cytogenet. 1994 Feb;72(2):161 [8143279] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6002-6 [8016105] Nature. 1994 Sep 15;371(6494):257-61 [8078588] Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8772-6 [8090721] Cancer Res. 1994 Nov 15;54(22):5831-6 [7954410] Genes Dev. 1994 Oct 15;8(20):2429-40 [7958907] Science. 1994 Dec 16;266(5192):1821-8 [7997877] Science. 1996 Mar 22;271(5256):1744-7 [8596939] Science. 1995 Mar 3;267(5202):1353-6 [7871434] J Biol Chem. 1996 Jul 5;271(27):16253-9 [8663151] Nature. 1981 Sep 3;293(5827):72-4 [6791032] Nature. 1986 Jul 3-9;322(6074):78-80 [3014349] Carcinogenesis. 1986 Nov;7(11):1845-8 [3769132] Nature. 1986 Oct 30-Nov 5;323(6091):822-4 [2430189] Mol Cell Biol. 1986 Jun;6(6):1917-25 [3785184] Proc Natl Acad Sci U S A. 1987 Apr;84(7):2029-32 [3104907] Cancer Res. 1988 Jan 1;48(1):165-9 [3121168] Carcinogenesis. 1988 Aug;9(8):1503-5 [3402048] Mol Carcinog. 1989;2(1):22-6 [2499343] Mol Endocrinol. 1990 Jan;4(1):46-52 [2157977] Cell. 1990 May 4;61(3):407-17 [2185890] Proc Natl Acad Sci U S A. 1990 Sep;87(17):6902-6 [1697691] Cancer Res. 1991 Aug 1;51(15):4097-101 [1855225] Oncogene. 1991 Dec;6(12):2363-9 [1766680] Cancer Res. 1992 Jun 1;52(11):3145-56 [1375535] Cancer Res. 1996 Aug 15;56(16):3645-50 [8706000] Nature. 1997 May 22;387(6631):417-22 [9163429] EMBO J. 1997 May 15;16(10):2621-33 [9184209] Cancer Res. 1997 Dec 15;57(24):5564-70 [9407968] Mol Cell Biol. 1998 Feb;18(2):1055-64 [9448003] Nature. 1998 Mar 19;392(6673):300-3 [9521327] Oncogene. 1998 Jul 9;17(1):25-34 [9671311] Science. 1998 Nov 20;282(5393):1497-501 [9822382] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3940-4 [10097142] Science. 1995 Jun 2;268(5215):1336-8 [7761852] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5545-9 [7777546] Science. 1995 Sep 15;269(5230):1575-7 [7667636] Methods Enzymol. 1995;254:3-20 [8531694] Cell. 1992 Sep 18;70(6):937-48 [1525830] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations. AN - 69413997; 10646828 AB - Depressed mood increases the relapse risk of abstinent alcoholics; its neurobiological correlates may include reduced serotonin and norepinephrine turnover rates and increased cortisol concentrations during detoxification stress. Neurosteroids such as dehydroepiandrosterone and its sulfate (DHEA and DHEA-S) may antagonize cortisol action and may have mood-elevating effects on their own. We measured severity of depression with Beck's Depression Inventory (BDI) and Hamilton's Depression Rating Scale (HDRS), plasma concentrations of cortisol, DHEA and DHEA-S, and CSF concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and the dopamine metabolite homovanillic acid (HVA) in 21 abstinent alcoholics after 4 weeks of abstinence and in 11 age-matched healthy control subjects. Only CSF MHPG concentrations were reduced in alcoholics compared to control subjects (41.4 +/- 6.6 vs. 53.3 +/- 8.6 pmol/ml). Self-rated depression was significantly correlated with CSF MHPG (Spearman's R = +0.57, P < 0.01), CSF 5-HIAA (R = +0.51, P < 0.05) and plasma cortisol concentrations (R = +0.50, P < 0.05). Negative correlations were found between DHEA-S concentrations and both self-rated depression (R = -0.45, P < 0.05) and observer-rated depression (R = -0.55, P < 0.05). The ratio of DHEA-S to cortisol serum concentrations was also negatively correlated with depression (BDI: R = -0.55, P < 0.01; HDRS: R = -0.63, P < 0.005). Anxiety (Spielberger's State Anxiety Scale) was only associated with CSF MHPG concentrations (R = +0.58, P < 0.01). Our findings point to the importance of noradrenergic dysfunction in the pathogenesis of depression among abstinent alcoholics and indicate that their mood states may also be modulated by a low DHEA-S to cortisol ratio, hypothetically indicative of low stress protection capacities. JF - Psychiatry research AU - Heinz, A AU - Weingartner, H AU - George, D AU - Hommer, D AU - Wolkowitz, O M AU - Linnoila, M AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA. heinza@as200.zi-mannheim.de Y1 - 1999/12/20/ PY - 1999 DA - 1999 Dec 20 SP - 97 EP - 106 VL - 89 IS - 2 SN - 0165-1781, 0165-1781 KW - Neurotransmitter Agents KW - 0 KW - Ethanol KW - 3K9958V90M KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Severity of Illness Index KW - Methoxyhydroxyphenylglycol -- metabolism KW - Humans KW - Hydroxyindoleacetic Acid -- metabolism KW - Hydrocortisone -- metabolism KW - Homovanillic Acid -- metabolism KW - Dehydroepiandrosterone -- metabolism KW - Psychiatric Status Rating Scales KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Statistics, Nonparametric KW - Female KW - Male KW - Neurotransmitter Agents -- cerebrospinal fluid KW - Substance Withdrawal Syndrome -- complications KW - Substance Withdrawal Syndrome -- metabolism KW - Depression -- blood KW - Depression -- cerebrospinal fluid KW - Ethanol -- metabolism KW - Substance Withdrawal Syndrome -- cerebrospinal fluid KW - Ethanol -- adverse effects KW - Neurotransmitter Agents -- metabolism KW - Depression -- metabolism KW - Neurotransmitter Agents -- blood KW - Substance Withdrawal Syndrome -- blood KW - Depression -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69413997?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=Severity+of+depression+in+abstinent+alcoholics+is+associated+with+monoamine+metabolites+and+dehydroepiandrosterone-sulfate+concentrations.&rft.au=Heinz%2C+A%3BWeingartner%2C+H%3BGeorge%2C+D%3BHommer%2C+D%3BWolkowitz%2C+O+M%3BLinnoila%2C+M&rft.aulast=Heinz&rft.aufirst=A&rft.date=1999-12-20&rft.volume=89&rft.issue=2&rft.spage=97&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-08 N1 - Date created - 2000-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of R651 mutations in the putative helix 6 of rat glucocorticoid receptors. AN - 69398180; 10630412 AB - Trypsin digestion of steroid-free, but not steroid-bound, rat glucocorticoid receptor (GR) has recently been reported to occur at arginine-651 (R651). This residue is close to the affinity labeled Cys-656 and thus could be a sensitive probe of steroid binding. This hypothesis is supported by the current model of the GR ligand binding domain (LBD), which is based on the X-ray structures of several related receptor LBDs and places R651 in the middle of the putative alpha-helix 6 (649-EQRMS-653 of rat GR), close to the bound steroid. To test this model, R651, which could be involved in hydrophilic and/or hydrogen bonding, was mutated to alanine (A), which favors alpha-helices, the helix breakers proline (P) and glycine (G), or tryptophan (W). All receptors were expressed at about the same level, as determined by Western blots, but the cell-free binding activity of R651P was reduced twofold. The cell-free binding affinities were all within a factor of 10 of wild type receptors. Whole cell biological activity with transiently transfected receptors was determined with a variety of GR agonists (dexamethasone and deacylcortivazol) or antagonists (dexamethasone mesylate, RU486, and progesterone). Reporters containing both simple (GRE) and complex (MMTV) enhancers were used to test for alterations in GR interactions with enhancer/promoter complexes. Surprisingly, no correlation was observed between biological activity and ability to preserve alpha-helical structures for each point mutation. Finally, similar trypsin digestion patterns indicated no major differences in the tertiary structure of the mutant receptors. Collectively, these results argue that the polar/ionizable residue R651 is not required for GR activity and is not part of an alpha-helix in the steroid-free or bound GR. The effect of these mutations on GR structure and activity may result from a cascade of initially smaller perturbations. These LBD alterations were the most varied for interactions with deacylcortivazol and RU 486, which have recently been predicted to be sub-optimal binders due to their large size. However, further analyses of ligand size versus affinity suggest that there is no narrowly defined optimal size for ligand binding, although larger ligands may be more sensitive to modifications of LBD structure. Finally, the changes in GR activity with the various mutations seem to result from altered LBD interactions with common, as opposed to enhancer specific, transcription factors. JF - Molecular and cellular endocrinology AU - Huang, Y AU - Simons, S S AD - Steroid Hormones Section, NIDDK/LMCB, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/12/20/ PY - 1999 DA - 1999 Dec 20 SP - 117 EP - 130 VL - 158 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Ligands KW - 0 KW - Receptors, Glucocorticoid KW - Steroids KW - Index Medicus KW - Animals KW - Models, Molecular KW - Steroids -- pharmacology KW - Amino Acid Sequence KW - Mutation, Missense KW - Protein Binding KW - Structure-Activity Relationship KW - Rats KW - Mutagenesis, Site-Directed KW - Blotting, Western KW - Enhancer Elements, Genetic KW - Protein Structure, Tertiary KW - Amino Acid Substitution KW - Cell Line KW - Steroids -- metabolism KW - Receptors, Glucocorticoid -- drug effects KW - Receptors, Glucocorticoid -- chemistry KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69398180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+endocrinology&rft.atitle=Functional+analysis+of+R651+mutations+in+the+putative+helix+6+of+rat+glucocorticoid+receptors.&rft.au=Huang%2C+Y%3BSimons%2C+S+S&rft.aulast=Huang&rft.aufirst=Y&rft.date=1999-12-20&rft.volume=158&rft.issue=1-2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-03 N1 - Date created - 2000-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 and tumor necrosis factor alpha regulate the expression of a mitochondrial chloride channel protein. AN - 69350486; 10593946 AB - A novel chloride intracellular channel (CLIC) gene, clone mc3s5/mtCLIC, has been identified from differential display analysis of differentiating mouse keratinocytes from p53+/+ and p53-/- mice. The 4.2-kilobase pair cDNA contains an open reading frame of 762 base pairs encoding a 253-amino acid protein with two putative transmembrane domains. mc3s5/mtCLIC protein shares extensive homology with a family of intracellular organelle chloride channels but is the first shown to be differentially regulated. mc3s5/mtCLIC mRNA is expressed to the greatest extent in vivo in heart, lung, liver, kidney, and skin, with reduced levels in some organs from p53-/- mice. mc3s5/mtCLIC mRNA and protein are higher in p53+/+ compared with p53-/- basal keratinocytes in culture, and both increase in differentiating keratinocytes independent of genotype. Overexpression of p53 in keratinocytes induces mc3s5/mtCLIC mRNA and protein. Exogenous human recombinant tumor necrosis factor alpha also up-regulates mc3s5/mtCLIC mRNA and protein in keratinocytes. Subcellular fractionation of keratinocytes indicates that both the green fluorescent protein-mc3s5 fusion protein and the endogenous mc3s5/mtCLIC are localized to the cytoplasm and mitochondria. Similarly, mc3s5/mtCLIC was localized to mitochondria and cytoplasmic fractions of rat liver homogenates. Furthermore, mc3s5/mtCLIC colocalized with cytochrome oxidase in keratinocyte mitochondria by immunofluorescence and was also detected in the cytoplasmic compartment. Sucrose gradient-purified mitochondria from rat liver confirmed this mitochondrial localization. This represents the first report of localization of a CLIC type chloride channel in mitochondria and the first indication that expression of an organellular chloride channel can be regulated by p53 and tumor necrosis factor alpha. JF - The Journal of biological chemistry AU - Fernández-Salas, E AU - Sagar, M AU - Cheng, C AU - Yuspa, S H AU - Weinberg, W C AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. esterf@nih.gov Y1 - 1999/12/17/ PY - 1999 DA - 1999 Dec 17 SP - 36488 EP - 36497 VL - 274 IS - 51 SN - 0021-9258, 0021-9258 KW - Chloride Channels KW - 0 KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Mice KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Rats KW - Base Sequence KW - Sequence Alignment KW - Genes, p53 KW - Cells, Cultured KW - Molecular Sequence Data KW - Mitochondria -- metabolism KW - Keratinocytes -- ultrastructure KW - Keratinocytes -- metabolism KW - Gene Expression Regulation KW - Chloride Channels -- biosynthesis KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Necrosis Factor-alpha -- metabolism KW - Tumor Suppressor Protein p53 -- metabolism KW - Tumor Necrosis Factor-alpha -- genetics KW - Chloride Channels -- genetics KW - Mitochondria -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69350486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=p53+and+tumor+necrosis+factor+alpha+regulate+the+expression+of+a+mitochondrial+chloride+channel+protein.&rft.au=Fern%C3%A1ndez-Salas%2C+E%3BSagar%2C+M%3BCheng%2C+C%3BYuspa%2C+S+H%3BWeinberg%2C+W+C&rft.aulast=Fern%C3%A1ndez-Salas&rft.aufirst=E&rft.date=1999-12-17&rft.volume=274&rft.issue=51&rft.spage=36488&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-27 N1 - Date created - 2000-01-27 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF102578; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 5-methylcytosine at HpaII sites in p53 is not hypermutable after UVC irradiation. AN - 69418910; 10656489 AB - Using a yeast based p53 functional assay we previously demonstrated that the UVC-induced p53 mutation spectrum appears to be indistinguishable from the one observed in Non Melanoma Skin Cancer (NMSC). However, position 742 (codon 248, CpG site) represented the major hot spot in NMSC but was not found mutated in the yeast system. In order to determine whether UVC-induced mutagenic events may be facilitated at methylated cytosine (5mC), a yeast expression vector harbouring a human wild-type p53 cDNA (pLS76) was methylated in vitro by HpaII methylase. Methylation induced 98% protection to HpaII endonuclease. Unmethylated and methylated pLS76 vectors were then UVC irradiated (lambda(max): 254 nm) and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. The results revealed that: (i) 5mC at HpaII sites did not cause any difference in the UVC-induced survival and/or mutagenicity; (ii) none of the 20 mutants derived from methylated pLS76 showed p53 mutations targeted at HpaII sites; (iii) the UVC-induced p53 mutation spectra derived from methylated and unmethylated pLS76 were indistinguishable not only when classes of mutations and hot spots were concerned, but also when compared through a rigorous statistical test to estimate their relatedness (P = 0.85); (iv) the presence of 5mC did not increase the formation of photo-lesions at codon 248, as determined by using a stop polymerase assay. Although based on a limited number of mutants, these results suggest that the mere presence of 5mC at position 742 does not cause a dramatic increase of its mutability after UVC irradiation. We propose that position 742 is a hot spot in NMSC either because of mutagenic events at 5mC caused by other UV components of solarlight and/or because not all the NMSC are directly correlated with UV mutagenesis but may have a "spontaneous" origin. JF - Mutation research AU - Monti, P AU - Inga, A AU - Scott, G AU - Aprile, A AU - Campomenosi, P AU - Menichini, P AU - Ottaggio, L AU - Viaggi, S AU - Abbondandolo, A AU - Burns, P A AU - Fronza, G AD - Mutagenesis Laboratory, National Cancer Institute (IST), Genova, UK. Y1 - 1999/12/16/ PY - 1999 DA - 1999 Dec 16 SP - 93 EP - 103 VL - 431 IS - 1 SN - 0027-5107, 0027-5107 KW - Codon KW - 0 KW - Tumor Suppressor Protein p53 KW - 5-Methylcytosine KW - 6R795CQT4H KW - Cytosine KW - 8J337D1HZY KW - Deoxyribonuclease HpaII KW - EC 3.1.21.- KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Ultraviolet Rays KW - Humans KW - CpG Islands KW - DNA Methylation -- radiation effects KW - Mutation KW - Tumor Suppressor Protein p53 -- radiation effects KW - Yeasts -- genetics KW - Yeasts -- radiation effects KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Cytosine -- analogs & derivatives KW - Yeasts -- metabolism KW - Deoxyribonuclease HpaII -- metabolism KW - Cytosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69418910?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=5-methylcytosine+at+HpaII+sites+in+p53+is+not+hypermutable+after+UVC+irradiation.&rft.au=Monti%2C+P%3BInga%2C+A%3BScott%2C+G%3BAprile%2C+A%3BCampomenosi%2C+P%3BMenichini%2C+P%3BOttaggio%2C+L%3BViaggi%2C+S%3BAbbondandolo%2C+A%3BBurns%2C+P+A%3BFronza%2C+G&rft.aulast=Monti&rft.aufirst=P&rft.date=1999-12-16&rft.volume=431&rft.issue=1&rft.spage=93&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-17 N1 - Date created - 2000-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ras oncogene-induced sensitization to 1-beta-D-arabinofuranosylcytosine. AN - 69390644; 10626790 AB - Human tumor cells containing ras oncogenes display enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) and other deoxycytidine analogues (H-M. Koo, et al., Cancer Res., 56: 5211-5216, 1996). Human tumor cell lines with or without a ras oncogene as well as a pair of isogenic cell lines with one containing an activated ras oncogene were used to study the basis for differential sensitivity. We found that human tumor cells containing ras oncogenes upon entry into the S phase of the cell cycle underwent apoptosis in response to Ara-C treatment. By contrast, human tumor cells harboring wild-type ras alleles were only delayed in the S phase when exposed to Ara-C. Thus, the ras oncogene specifically renders human cells more sensitive to Ara-C by preventing S-phase arrest. This may occur by the ras oncogene compromising an S-phase checkpoint. JF - Cancer research AU - Koo, H M AU - McWilliams, M J AU - Alvord, W G AU - Vande Woude, G F AD - Advanced Bioscience Laboratories Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6057 EP - 6062 VL - 59 IS - 24 SN - 0008-5472, 0008-5472 KW - Antimetabolites, Antineoplastic KW - 0 KW - Cytarabine KW - 04079A1RDZ KW - DNA KW - 9007-49-2 KW - Deoxycytidine Kinase KW - EC 2.7.1.74 KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Deoxycytidine Kinase -- biosynthesis KW - Tumor Cells, Cultured KW - Transfection KW - Humans KW - DNA -- metabolism KW - S Phase KW - Cell Transformation, Neoplastic KW - Cytarabine -- pharmacology KW - Apoptosis KW - Genes, ras -- physiology KW - Cytarabine -- metabolism KW - Antimetabolites, Antineoplastic -- metabolism KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69390644?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Ras+oncogene-induced+sensitization+to+1-beta-D-arabinofuranosylcytosine.&rft.au=Koo%2C+H+M%3BMcWilliams%2C+M+J%3BAlvord%2C+W+G%3BVande+Woude%2C+G+F&rft.aulast=Koo&rft.aufirst=H&rft.date=1999-12-15&rft.volume=59&rft.issue=24&rft.spage=6057&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-24 N1 - Date created - 2000-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential roles of the tandem C1 domains of protein kinase C delta in the biphasic down-regulation induced by bryostatin 1. AN - 69390490; 10626804 AB - Bryostatin 1 (Bryo), currently in clinical trials, has been shown to induce a biphasic concentration-response curve for down-regulating protein kinase C (PKC) delta, with protection of the enzyme from down-regulation at high Bryo doses. In our ongoing studies to identify the basis for this unique behavior of PKCdelta, we examined the participation of the two ligand binding sites (C1a and C1b) in the regulatory domain of the enzyme. Three mutants of PKCdelta prepared by introducing a point mutation in either C1a or Clb or both C1a and Clb were overexpressed in NIH 3T3 cells. All of the constructs retained a biphasic response to down-regulation assessed after 24-h treatment with Bryo. However, the roles of the individual C1 domains were different for the two phases of the response. For down-regulation, both the C1a and the C1b mutants displayed equivalent 3-4-fold reductions in their affinities for the ligand. For protection from down-regulation, a reduced protection was observed for the C1a mutant, which showed a broader biphasic curve compared with those for wild-type PKCdelta and the Clb mutant. Like wild-type PKCdelta, all of the mutants showed the same subcellular partitioning of the protected enzyme to the particulate fraction of the cells, arguing against changes in sensitivity to Bryo due to differences in localization. Likewise, relatively similar patterns of localization were observed using green fluorescent protein-PKCdelta constructs. We conclude that the C1 domains of PKCdelta do not have equivalent roles in inducing protection against Bryo-induced down-regulation. The C1a domain plays a critical role in conferring the degree of protection at high concentrations of Bryo. Elucidation of the differential effect of Bryo on PKCdelta may suggest strategies for the design of novel ligands with Bryo-like activities. JF - Cancer research AU - Lorenzo, P S AU - Bögi, K AU - Hughes, K M AU - Beheshti, M AU - Bhattacharyya, D AU - Garfield, S H AU - Pettit, G R AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6137 EP - 6144 VL - 59 IS - 24 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Bryostatins KW - Isoenzymes KW - Lactones KW - Ligands KW - Macrolides KW - Tritium KW - 10028-17-8 KW - Phorbol 12,13-Dibutyrate KW - 37558-16-0 KW - bryostatin 1 KW - 37O2X55Y9E KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Phorbol 12,13-Dibutyrate -- metabolism KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Down-Regulation KW - Protein Conformation KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- genetics KW - Antineoplastic Agents -- metabolism KW - Protein Kinase C -- chemistry KW - Protein Kinase C -- biosynthesis KW - Isoenzymes -- genetics KW - Lactones -- metabolism KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69390490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Differential+roles+of+the+tandem+C1+domains+of+protein+kinase+C+delta+in+the+biphasic+down-regulation+induced+by+bryostatin+1.&rft.au=Lorenzo%2C+P+S%3BB%C3%B6gi%2C+K%3BHughes%2C+K+M%3BBeheshti%2C+M%3BBhattacharyya%2C+D%3BGarfield%2C+S+H%3BPettit%2C+G+R%3BBlumberg%2C+P+M&rft.aulast=Lorenzo&rft.aufirst=P&rft.date=1999-12-15&rft.volume=59&rft.issue=24&rft.spage=6137&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-24 N1 - Date created - 2000-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. AN - 69389253; 10626795 AB - The promoter of the hTERT gene encoding the catalytic subunit of telomerase was recently cloned and has a dense CG-rich CpG island, suggesting a role for methylation in regulation of hTERT expression. In this study, we have initiated the analysis of the regulation of hTERT expression by examining the methylation status of up to 72 CpG sites extending from 500 bases upstream of the transcriptional start site of the hTERT gene into the first exon in 37 cell lines. These cell lines represent a variety of cell and tissue types, including normal, immortalized, and cancer cell lines from lung, breast, and other tissues. Using bisulfite genomic sequencing, we did not find a generalized pattern of site-specific or region-specific methylation that correlated with expression of the hTERT gene: most of the hTERT-negative normal cells and about one-third of the hTERT-expressing cell lines had the unmethylated/hypomethylated promoter, whereas the other hTERT-expressing cell lines showed partial or total methylation of the promoter. The promoter of one hTERT-negative fibroblast cell line, SUSM-1, was methylated at all sites examined. Treatment of SUSM-1 cells with the demethylating agent 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A induced the cells to express hTERT, suggesting a potential role for DNA methylation and/or histone deacetylation in negative regulation of hTERT. This study indicates that there are multiple levels of regulation of hTERT expression in CpG island methylation-dependent and -independent manners. JF - Cancer research AU - Devereux, T R AU - Horikawa, I AU - Anna, C H AU - Annab, L A AU - Afshari, C A AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. devereux@niehs.nih.gov Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6087 EP - 6090 VL - 59 IS - 24 SN - 0008-5472, 0008-5472 KW - Chromatin KW - 0 KW - DNA-Binding Proteins KW - Sulfites KW - telomerase RNA KW - RNA KW - 63231-63-0 KW - Telomerase KW - EC 2.7.7.49 KW - hydrogen sulfite KW - OJ9787WBLU KW - Index Medicus KW - Tumor Cells, Cultured KW - Sulfites -- chemistry KW - Humans KW - Chromatin -- chemistry KW - Chromatin -- physiology KW - Cell Line KW - Promoter Regions, Genetic KW - Gene Expression Regulation, Enzymologic KW - DNA Methylation KW - Telomerase -- genetics KW - Telomerase -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69389253?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=DNA+methylation+analysis+of+the+promoter+region+of+the+human+telomerase+reverse+transcriptase+%28hTERT%29+gene.&rft.au=Devereux%2C+T+R%3BHorikawa%2C+I%3BAnna%2C+C+H%3BAnnab%2C+L+A%3BAfshari%2C+C+A%3BBarrett%2C+J+C&rft.aulast=Devereux&rft.aufirst=T&rft.date=1999-12-15&rft.volume=59&rft.issue=24&rft.spage=6087&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-24 N1 - Date created - 2000-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunosuppressants FK506 and rapamycin have different effects on the biosynthesis of cytoplasmic actin during the early period of T cell activation. AN - 69346539; 10585867 AB - FK506 and rapamycin are immunosuppressants that interfere with T cell activation. FK506 inhibits early events of T cell activation such as the induction of cytokine transcription, whereas rapamycin inhibits later interleukin 2 signalling events. However, both reagents either directly or indirectly reduce protein synthesis. Therefore a kinetic study was conducted in human primary T lymphocytes examining increased synthesis of proteins stimulated by either ionomycin+phorbol myristate acetate (PMA) or PMA alone. Three patterns of protein expression were observed. Synthesis of one group of proteins had enhanced synthesis with FK506, but reduced synthesis with rapamycin. A second group had reduced synthesis with rapamycin and either no change or a slight reduction with FK506 and a third group had reduction with both FK506 and rapamycin. One major protein of the first group, p42, had a rapid increase in synthesis that decreased by 8 h. Its synthesis was strongly enhanced by FK506, but reduced by rapamycin after ionomycin+PMA stimulation. In contrast, this protein was strongly induced by PMA alone in these cells and not affected by FK506 treatment, but still reduced by rapamycin. p42 was identified as cytoplasmic actin. mRNA levels of both gamma- and beta-actin were found to be enhanced with FK506 treatment suggesting that regulation of actin was at a transcriptional or post-transcriptional level. Results with actinomycin D indicated that FK506 is regulating actin biosynthesis at the post-transcriptional level. Rapamycin, however, appeared to be operating at the level of translation. JF - The Biochemical journal AU - Miyamoto, S AU - Safer, B AD - Molecular Hematology Branch, Section on Protein and RNA Biosynthesis, National Heart, Lung and Blood Institute, Bldg. 10, Room 7D18, Bethesda, MD 20892-21654, USA. smiyamot@ucdavis.edu Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 803 EP - 812 VL - 344 Pt 3 SN - 0264-6021, 0264-6021 KW - Actins KW - 0 KW - Immunosuppressive Agents KW - Dactinomycin KW - 1CC1JFE158 KW - Ionomycin KW - 56092-81-0 KW - Cycloheximide KW - 98600C0908 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Sirolimus KW - W36ZG6FT64 KW - Tacrolimus KW - WM0HAQ4WNM KW - Index Medicus KW - Protein Biosynthesis -- drug effects KW - Dactinomycin -- pharmacology KW - Transcription, Genetic -- drug effects KW - Humans KW - Cycloheximide -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Ionomycin -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Tacrolimus -- pharmacology KW - Sirolimus -- pharmacology KW - T-Lymphocytes -- drug effects KW - Actins -- biosynthesis KW - Immunosuppressive Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69346539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Immunosuppressants+FK506+and+rapamycin+have+different+effects+on+the+biosynthesis+of+cytoplasmic+actin+during+the+early+period+of+T+cell+activation.&rft.au=Miyamoto%2C+S%3BSafer%2C+B&rft.aulast=Miyamoto&rft.aufirst=S&rft.date=1999-12-15&rft.volume=344+Pt+3&rft.issue=&rft.spage=803&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-17 N1 - Date created - 2000-03-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1993 Aug;122(4):825-32 [8349732] Immunology. 1992 Jul;76(3):465-71 [1388136] Mol Biol Cell. 1993 Dec;4(12):1225-38 [8167406] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4441-5 [8183928] Science. 1994 Oct 28;266(5185):653-6 [7939721] Adv Exp Med Biol. 1994;358:183-9 [7801804] Ther Drug Monit. 1995 Dec;17(6):584-91 [8588225] Life Sci. 1996;58(5):373-95 [8594303] Biochem J. 1996 May 1;315 ( Pt 3):791-8 [8645159] J Neurosci. 1998 Jan 1;18(1):251-65 [9412505] J Biol Chem. 1998 May 29;273(22):13367-70 [9593662] Curr Biol. 1998 May 7;8(10):563-72 [9601640] Nature. 1970 Aug 15;227(5259):680-5 [5432063] Proc Natl Acad Sci U S A. 1979 Mar;76(3):1298-302 [286312] Proc Natl Acad Sci U S A. 1984 Dec;81(23):7476-80 [6334309] Nature. 1985 Jan 24-30;313(6000):318-20 [3918270] Nucleic Acids Res. 1986 Jul 11;14(13):5275-94 [3737401] J Immunol. 1987 Sep 1;139(5):1393-9 [3114365] Eur J Biochem. 1987 Dec 30;170(1-2):87-92 [3691536] Biochem Cell Biol. 1987 Jun;65(6):565-75 [3426834] Mol Cell Biol. 1988 Apr;8(4):1775-89 [2837653] J Cell Physiol. 1988 Nov;137(2):329-36 [3263971] J Immunol. 1989 Jul 15;143(2):718-26 [2472451] Transplantation. 1990 Apr;49(4):798-802 [1691537] Proc Natl Acad Sci U S A. 1990 Dec;87(23):9231-5 [2123553] Science. 1991 Jan 18;251(4991):283-7 [1702904] New Biol. 1990 Aug;2(8):663-72 [2282365] Crit Rev Immunol. 1990;10(4):347-91 [1704705] Biochim Biophys Acta. 1991 Mar 19;1092(1):124-7 [2009307] Immunology. 1991 Apr;72(4):544-9 [1709916] Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6229-33 [1712484] Cell. 1991 Aug 23;66(4):807-15 [1715244] J Immunol. 1992 Feb 15;148(4):1049-54 [1371128] Nature. 1992 Jul 2;358(6381):70-3 [1614535] Anal Biochem. 1992 Mar;201(2):255-64 [1632512] Ann N Y Acad Sci. 1993 Nov 30;696:20-30 [7509131] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenovirus-mediated expression of human coagulation factor IX in the rhesus macaque is associated with dose-limiting toxicity. AN - 69344993; 10590040 AB - We used a first-generation adenovirus vector (AVC3FIX5) to assess whether human factor IX could be expressed and detected in the rhesus macaque, which we have shown does not make high-titer antibodies to human factor IX protein. Three animals received 1 x 10(10) to 1 x 10(11) plaque-forming units per kilogram by intravenous injection. Human factor IX was present within 24 hours of vector administration and peaked 4 days later at 4,000 ng/mL in the high-dose recipient, and lower levels were seen in the intermediate-dose recipient. No human factor IX was detected in the low-dose recipient's plasma. Serum cytokine analysis and early hypoferremia suggested a dose-dependent acute-phase response to the vector. Human factor IX was detectable in rhesus plasma for 2 to 3 weeks for the high- and intermediate-dose recipients, but disappeared concomitant with high-titer antihuman factor IX antibody development. There was substantial, dose-dependent, dose-limiting liver toxicity that was manifest as elevated serum transaminase levels, hyperbilirubinemia, hypoalbuminemia, and prolongation of clotting times. Of particular interest was prolongation of the thrombin clotting time, an indicator of decreased fibrinogen or fibrinogen dysfunction. All evidence of liver toxicity resolved except for persistent hypofibrinogenemia in the high-dose recipient, indicating possible permanent liver damage. Our data suggest a narrow therapeutic window for first-generation adenovirus-mediated gene transfer. The development of antihuman factor IX antibodies and abnormalities of fibrinogen in the rhesus macaque is of concern for application of adenovirus (or other viral) vectors to hemophilia gene therapy. JF - Blood AU - Lozier, J N AU - Metzger, M E AU - Donahue, R E AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, Bethesda, MD, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 3968 EP - 3975 VL - 94 IS - 12 SN - 0006-4971, 0006-4971 KW - Factor IX KW - 9001-28-9 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Macaca mulatta KW - Adenoviridae KW - Gene Transfer Techniques -- adverse effects KW - Factor IX -- toxicity KW - Factor IX -- biosynthesis KW - Genetic Vectors -- adverse effects KW - Factor IX -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69344993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Adenovirus-mediated+expression+of+human+coagulation+factor+IX+in+the+rhesus+macaque+is+associated+with+dose-limiting+toxicity.&rft.au=Lozier%2C+J+N%3BMetzger%2C+M+E%3BDonahue%2C+R+E%3BMorgan%2C+R+A&rft.aulast=Lozier&rft.aufirst=J&rft.date=1999-12-15&rft.volume=94&rft.issue=12&rft.spage=3968&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-10 N1 - Date created - 2000-01-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Blood. 1999 Dec 15;94(12):3965-7 [10590039] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of antigen-specific T lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens. AN - 69338672; 10586088 AB - The cloning of cancer Ags recognized by T cells has provided potentially new tools to enhance immunity against metastatic cancer. The biological monitoring of effective immunization has, however, remained a dilemma. We describe here a sensitive molecular quantitation methodology that allows analysis of in vivo immune response to vaccination. Metastatic melanoma patients were immunized with a synthetically modified peptide epitope (209-2M) from the melanoma self-Ag gp100. Using serial gene expression analysis, we report functional evidence of vaccine-induced CTL reactivity in fresh cells obtained directly from the peripheral blood of postimmunized patients. Further, we demonstrate in vivo localization of vaccine-induced immune response within the tumor microenvironment. The results of these molecular assays provide direct evidence that peptide immunization in humans can result in tumor-specific CTL that localize to metastatic sites. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Kammula, U S AU - Lee, K H AU - Riker, A I AU - Wang, E AU - Ohnmacht, G A AU - Rosenberg, S A AU - Marincola, F M AD - Surgery Branch, Clinical Center, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6867 EP - 6875 VL - 163 IS - 12 SN - 0022-1767, 0022-1767 KW - Cancer Vaccines KW - 0 KW - Epitopes, T-Lymphocyte KW - Peptides KW - RNA, Messenger KW - Interferon-gamma KW - 82115-62-6 KW - Abridged Index Medicus KW - Index Medicus KW - Cancer Vaccines -- administration & dosage KW - Interferon-gamma -- genetics KW - Peptides -- administration & dosage KW - Humans KW - Cancer Vaccines -- therapeutic use KW - Peptides -- immunology KW - Interferon-gamma -- biosynthesis KW - Melanoma -- chemistry KW - Biopsy, Needle KW - Melanoma -- immunology KW - RNA, Messenger -- biosynthesis KW - Peptides -- therapeutic use KW - Cancer Vaccines -- immunology KW - Fluorescent Antibody Technique, Direct KW - Melanoma -- pathology KW - Tumor Cells, Cultured KW - Cytotoxicity Tests, Immunologic KW - Melanoma -- therapy KW - T-Lymphocyte Subsets -- metabolism KW - T-Lymphocyte Subsets -- immunology KW - Leukocytes, Mononuclear -- metabolism KW - Gene Expression Regulation, Neoplastic -- immunology KW - Leukocytes, Mononuclear -- immunology KW - Epitopes, T-Lymphocyte -- immunology KW - Epitopes, T-Lymphocyte -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69338672?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Functional+analysis+of+antigen-specific+T+lymphocytes+by+serial+measurement+of+gene+expression+in+peripheral+blood+mononuclear+cells+and+tumor+specimens.&rft.au=Kammula%2C+U+S%3BLee%2C+K+H%3BRiker%2C+A+I%3BWang%2C+E%3BOhnmacht%2C+G+A%3BRosenberg%2C+S+A%3BMarincola%2C+F+M&rft.aulast=Kammula&rft.aufirst=U&rft.date=1999-12-15&rft.volume=163&rft.issue=12&rft.spage=6867&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation. AN - 69338512; 10586077 AB - Trp-Lys-Tyr-Val-D-Met (WKYMVm) is a synthetic leukocyte-activating peptide postulated to use seven-transmembrane, G protein-coupled receptor(s). In the study to characterize the receptor(s) for WKYMVm, we found that this peptide induced marked chemotaxis and calcium flux in human phagocytes. The signaling induced by WKYMVm in phagocytes was attenuated by high concentrations of the bacterial chemotactic peptide fMLP, suggesting that WKYMVm might use receptor(s) for fMLP. This hypothesis was tested by using cells over expressing genes encoding two seven-transmembrane receptors, formyl peptide receptor (FPR) and formyl peptide receptor-like 1 (FPRL1), which are with high and low affinity for fMLP, respectively. Both FPR- and FPRL1-expressing cells mobilized calcium in response to picomolar concentrations of WKYMVm. While FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm, nanomolar concentrations of the peptide were required to induce migration of FPR-expressing cells. In contrast, fMLP elicited both calcium flux and chemotaxis only in FPR-expressing cells with an efficacy comparable with WKYMVm. Thus, WKYMVm uses both FPR and FPRL1 to stimulate phagocytes with a markedly higher efficacy for FPRL1. Our study suggests that FPR and FPRL1 in phagocytes react to a broad spectrum of agonists and WKYMVm as a remarkably potent agonist provides a valuable tool for studying leukocyte signaling via these receptors. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Le, Y AU - Gong, W AU - Li, B AU - Dunlop, N M AU - Shen, W AU - Su, S B AU - Ye, R D AU - Wang, J M AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6777 EP - 6784 VL - 163 IS - 12 SN - 0022-1767, 0022-1767 KW - FPR2 protein, human KW - 0 KW - Membrane Proteins KW - Oligopeptides KW - Receptors, Formyl Peptide KW - Receptors, Immunologic KW - Receptors, Lipoxin KW - Receptors, Peptide KW - Trp-Lys-Tyr-Met-Val-Met KW - Virulence Factors, Bordetella KW - Cholera Toxin KW - 9012-63-9 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Abridged Index Medicus KW - Index Medicus KW - Virulence Factors, Bordetella -- pharmacology KW - Transfection KW - Cell Migration Inhibition KW - Humans KW - GTP-Binding Proteins -- metabolism KW - Chemotaxis, Leukocyte -- immunology KW - Cholera Toxin -- pharmacology KW - Phagocytosis -- immunology KW - GTP-Binding Proteins -- immunology KW - Receptors, Peptide -- metabolism KW - Neutrophils -- immunology KW - Membrane Proteins -- immunology KW - Membrane Proteins -- metabolism KW - Receptors, Peptide -- immunology KW - Oligopeptides -- immunology KW - Membrane Proteins -- genetics KW - Oligopeptides -- chemical synthesis KW - Receptors, Immunologic -- genetics KW - Neutrophils -- metabolism KW - Receptors, Immunologic -- immunology KW - Monocytes -- physiology KW - Receptors, Immunologic -- metabolism KW - Monocytes -- immunology KW - Monocytes -- metabolism KW - Receptors, Peptide -- genetics KW - Oligopeptides -- metabolism KW - Neutrophils -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69338512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Utilization+of+two+seven-transmembrane%2C+G+protein-coupled+receptors%2C+formyl+peptide+receptor-like+1+and+formyl+peptide+receptor%2C+by+the+synthetic+hexapeptide+WKYMVm+for+human+phagocyte+activation.&rft.au=Le%2C+Y%3BGong%2C+W%3BLi%2C+B%3BDunlop%2C+N+M%3BShen%2C+W%3BSu%2C+S+B%3BYe%2C+R+D%3BWang%2C+J+M&rft.aulast=Le&rft.aufirst=Y&rft.date=1999-12-15&rft.volume=163&rft.issue=12&rft.spage=6777&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opioid peptide receptor studies. 10. Nor-BNI differentially inhibits kappa receptor agonist-induced G-protein activation in the guinea pig caudate: further evidence of kappa receptor heterogeneity. AN - 69211119; 10529720 AB - There is strong evidence supporting the existence of multiple kappa receptors. Previous studies proposed that U69,593 and (+)-tifluadom act on different kappa receptor subtypes, kappa(1) (kappa(1)) and kappa(2) (kappa(2)), respectively. In this study, we investigated the effects of the kappa selective antagonist nor-binaltorphimine (Nor-BNI) on U69,593- and (+)-tifluadom-induced receptor-mediated stimulation of [(35)S]-GTP-gamma-S binding in the guinea pig caudate. The IC(50) value of Nor-BNI in the presence of a stimulating concentration of U69,593 (1 microM) was 0.19+/-0.02; while the IC(50) for Nor-BNI in the presence of (+)-tifluadom (1 microM) was 13.9+/- 1.62 nM. The mu-opioid receptor antagonist CTAP (10,000 nM) significantly reduced (+)-tifluadom-stimulated [(35)S]-GTP-gamma-S binding in rat brain sections and guinea pig brain membranes, indicating that (+)-tifluadom has mu agonist activity. Under conditions in which the mu agonist activity of (+)-tifluadom was blocked by 1000 nM CTAP the Ki value for Nor-BNI for inhibition of U69,593-stimulated [(35)S]-GTP-gamma-S binding was 0.036+/-.004 nM, whereas, its Ki value for the (+)-tifluadom-stimulated [(35)S]-GTP-gamma-S binding was 0.27+/-.015 nM. These results suggest that (+)-tifluadom and U69,593 activate pharmacologically different receptors. This study provides functional evidence in support of kappa receptor heterogeneity. JF - Synapse (New York, N.Y.) AU - Heyliger, S O AU - Jackson, C AU - Rice, K C AU - Rothman, R B AD - Clinical Psychopharmacology Section, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, P. O. Box 5180, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 256 EP - 265 VL - 34 IS - 4 SN - 0887-4476, 0887-4476 KW - Benzeneacetamides KW - 0 KW - CTAP octapeptide KW - Oligopeptides KW - Peptide Fragments KW - Peptides KW - Pyrrolidines KW - Receptors, Opioid, delta KW - Receptors, Opioid, kappa KW - Receptors, Opioid, mu KW - kappa(1) opioid receptor KW - kappa(2) opioid receptor KW - tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Benzodiazepines KW - 12794-10-4 KW - norbinaltorphimine KW - 36OOQ86QM1 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Somatostatin KW - 51110-01-1 KW - Naltrexone KW - 5S6W795CQM KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - U 69593 KW - J5S4K6TKTG KW - tifluadom KW - TF8X866L0I KW - Index Medicus KW - Animals KW - Receptors, Opioid, delta -- antagonists & inhibitors KW - Pyrrolidines -- antagonists & inhibitors KW - Dose-Response Relationship, Drug KW - Guinea Pigs KW - Brain -- drug effects KW - Receptors, Opioid, delta -- agonists KW - Brain -- metabolism KW - Receptors, Opioid, mu -- metabolism KW - Peptides -- pharmacology KW - Rats KW - Benzodiazepines -- antagonists & inhibitors KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- -- pharmacology KW - Receptors, Opioid, mu -- agonists KW - Receptors, Opioid, mu -- antagonists & inhibitors KW - In Vitro Techniques KW - Receptors, Opioid, delta -- metabolism KW - Pyrrolidines -- pharmacology KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Oligopeptides -- pharmacology KW - Inhibitory Concentration 50 KW - Benzodiazepines -- pharmacology KW - Caudate Nucleus -- metabolism KW - Receptors, Opioid, kappa -- agonists KW - GTP-Binding Proteins -- metabolism KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Naltrexone -- analogs & derivatives KW - Naltrexone -- pharmacology KW - Receptors, Opioid, kappa -- metabolism KW - Caudate Nucleus -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69211119?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Opioid+peptide+receptor+studies.+10.+Nor-BNI+differentially+inhibits+kappa+receptor+agonist-induced+G-protein+activation+in+the+guinea+pig+caudate%3A+further+evidence+of+kappa+receptor+heterogeneity.&rft.au=Heyliger%2C+S+O%3BJackson%2C+C%3BRice%2C+K+C%3BRothman%2C+R+B&rft.aulast=Heyliger&rft.aufirst=S&rft.date=1999-12-15&rft.volume=34&rft.issue=4&rft.spage=256&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-30 N1 - Date created - 1999-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Adjacent Flanking Region Plays a Critical Role in Facilitating the Presentation of the Listeria monocytogenes Product lemA to H2 M3 super(wt)-Restricted, Peptide-Specific Murine CD8 Cells AN - 17438189; 4658664 AB - Mice infected with Listeria monocytogenes (LM) generate CD8 effectors specific for f-MIGWII, the amino terminus of the bacterial product lemA presented by the class Ib MHC molecule H2 M3 super(wt). lemA has several distinctive properties: 1) it is readily presented as an exogenous Ag in the absence of bacterial infection; 2) it is processed by a TAP-independent pathway, which is sensitive to chloroquine, pepstatin, and brefeldin; and 3) the immunogenic portion of the molecule is extremely resistant to proteolytic degradation even by proteinase K. To assess the structural basis for these findings, we expressed a truncated variant (t-lemA) containing the amino-terminal hexapeptide and the subsequent 27 amino acids linked to a histidine tail in Escherichia coli, and purified the product by affinity chromatography. Purified t-lemA could be presented to f-MIGWII-specific effectors by macrophages and fibroblasts at 1-10 nM. Unlike f-MIGWII, which binds directly to H2 M3 super(wt), t-lemA required processing by a chloroquine-, pepstatin-, and brefeldin-sensitive pathway. Brefeldin sensitivity often implies endogenous processing in the cytoplasm, but several lines of evidence suggest translocation to the cytoplasm and proteosomal degradation are not critical for t-lemA presentation. Unlike f-MIGWII, t-lemA was profoundly resistant to proteinase K, and, using super(35)S-labeled t-lemA, we could identify the region from position 1 to similar to 30 as the protease-resistant element. Thus, the hydrophobic peptide sequence following f-MIGWII can account for the unusual properties of lemA noted above. Analogous modification could be used to alter the properties of other peptide Ags presented by class I MHC products. JF - Journal of Immunology AU - Kurlander, R J AU - Chao, E AU - Fields, J AU - Nataraj, C AD - Clinical Center, National Institutes of Health, Building 10, Room 2C/390, 10 Center Drive, Bethesda, MD 20892-1508, USA, rkurlander@nih.gov Y1 - 1999/12/15/ PY - 1999 DA - 1999 Dec 15 SP - 6741 EP - 6747 VL - 163 IS - 12 SN - 0022-1767, 0022-1767 KW - mice KW - immunology KW - CD8 antigen KW - Listeria monocytogenes KW - lemA protein KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Major histocompatibility complex KW - Antigen presentation KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17438189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=The+Adjacent+Flanking+Region+Plays+a+Critical+Role+in+Facilitating+the+Presentation+of+the+Listeria+monocytogenes+Product+lemA+to+H2+M3+super%28wt%29-Restricted%2C+Peptide-Specific+Murine+CD8+Cells&rft.au=Kurlander%2C+R+J%3BChao%2C+E%3BFields%2C+J%3BNataraj%2C+C&rft.aulast=Kurlander&rft.aufirst=R&rft.date=1999-12-15&rft.volume=163&rft.issue=12&rft.spage=6741&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Listeria monocytogenes; Major histocompatibility complex; Antigen presentation ER - TY - JOUR T1 - Botulinum neurotoxin A blocks synaptic vesicle exocytosis but not endocytosis at the nerve terminal. AN - 69366844; 10601338 AB - The supply of synaptic vesicles in the nerve terminal is maintained by a temporally linked balance of exo- and endocytosis. Tetanus and botulinum neurotoxins block neurotransmitter release by the enzymatic cleavage of proteins identified as critical for synaptic vesicle exocytosis. We show here that botulinum neurotoxin A is unique in that the toxin-induced block in exocytosis does not arrest vesicle membrane endocytosis. In the murine spinal cord, cell cultures exposed to botulinum neurotoxin A, neither K(+)-evoked neurotransmitter release nor synaptic currents can be detected, twice the ordinary number of synaptic vesicles are docked at the synaptic active zone, and its protein substrate is cleaved, which is similar to observations with tetanus and other botulinal neurotoxins. In marked contrast, K(+) depolarization, in the presence of Ca(2+), triggers the endocytosis of the vesicle membrane in botulinum neurotoxin A-blocked cultures as evidenced by FM1-43 staining of synaptic terminals and uptake of HRP into synaptic vesicles. These experiments are the first demonstration that botulinum neurotoxin A uncouples vesicle exo- from endocytosis, and provide evidence that Ca(2+) is required for synaptic vesicle membrane retrieval. JF - The Journal of cell biology AU - Neale, E A AU - Bowers, L M AU - Jia, M AU - Bateman, K E AU - Williamson, L C AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. eneale@codon.nih.gov Y1 - 1999/12/13/ PY - 1999 DA - 1999 Dec 13 SP - 1249 EP - 1260 VL - 147 IS - 6 SN - 0021-9525, 0021-9525 KW - FM1 43 KW - 0 KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Pyridinium Compounds KW - Quaternary Ammonium Compounds KW - R-SNARE Proteins KW - Snap25 protein, mouse KW - Synaptosomal-Associated Protein 25 KW - Tetanus Toxin KW - tetanospasmin KW - 11032-48-7 KW - Tetrodotoxin KW - 4368-28-9 KW - Horseradish Peroxidase KW - EC 1.11.1.- KW - Metalloendopeptidases KW - EC 3.4.24.- KW - Botulinum Toxins, Type A KW - EC 3.4.24.69 KW - Potassium KW - RWP5GA015D KW - Calcium KW - SY7Q814VUP KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Nerve Tissue Proteins -- analysis KW - Animals KW - Metalloendopeptidases -- pharmacology KW - Intracellular Membranes -- drug effects KW - Neurons -- drug effects KW - Calcium -- pharmacology KW - Membrane Proteins -- analysis KW - Calcium -- metabolism KW - Pyridinium Compounds -- metabolism KW - Potassium -- pharmacology KW - Intracellular Membranes -- metabolism KW - Spinal Cord -- cytology KW - Quaternary Ammonium Compounds -- metabolism KW - Glycine -- metabolism KW - Mice KW - Spinal Cord -- embryology KW - Horseradish Peroxidase -- metabolism KW - Cells, Cultured KW - Neurons -- cytology KW - Mice, Inbred C57BL KW - Membrane Potentials -- drug effects KW - Tetrodotoxin -- pharmacology KW - Tetanus Toxin -- pharmacology KW - Intracellular Membranes -- ultrastructure KW - Female KW - Exocytosis -- drug effects KW - Presynaptic Terminals -- ultrastructure KW - Presynaptic Terminals -- drug effects KW - Synaptic Vesicles -- metabolism KW - Synaptic Vesicles -- ultrastructure KW - Endocytosis -- drug effects KW - Synaptic Vesicles -- drug effects KW - Botulinum Toxins, Type A -- pharmacology KW - Presynaptic Terminals -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69366844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Botulinum+neurotoxin+A+blocks+synaptic+vesicle+exocytosis+but+not+endocytosis+at+the+nerve+terminal.&rft.au=Neale%2C+E+A%3BBowers%2C+L+M%3BJia%2C+M%3BBateman%2C+K+E%3BWilliamson%2C+L+C&rft.aulast=Neale&rft.aufirst=E&rft.date=1999-12-13&rft.volume=147&rft.issue=6&rft.spage=1249&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-11 N1 - Date created - 2000-01-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1969 Jul;42(1):202-20 [4182372] Nature. 1992 Oct 29;359(6398):832-5 [1331807] J Cell Biol. 1973 May;57(2):499-524 [4348791] J Neurophysiol. 1977 Sep;40(5):1132-50 [333062] Brain Res. 1978 Aug 25;152(2):265-82 [209872] Brain Res. 1980 Mar 10;185(2):455-9 [7188876] J Cell Biol. 1980 Oct;87(1):297-303 [6252215] Prog Neurobiol. 1980;14(2-3):99-119 [6999538] Proc Natl Acad Sci U S A. 1981 Feb;78(2):1014-8 [7015327] J Neurosci. 1983 Nov;3(11):2310-23 [6631482] Brain Res. 1985 Dec 23;360(1-2):318-24 [3000532] J Neurophysiol. 1987 Jan;57(1):121-31 [3031230] Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):1-7 [2883583] Neuroscience. 1988 Jun;25(3):1095-106 [3405427] J Cell Biol. 1988 Dec;107(6 Pt 2):2717-27 [3144557] Nature. 1993 Mar 25;362(6418):318-24 [8455717] Nature. 1993 Jul 22;364(6435):346-9 [8332193] Cell. 1993 Sep 10;74(5):855-61 [8374953] Neuron. 1993 Oct;11(4):713-24 [8398156] J Cell Biol. 1994 Mar;124(5):667-75 [8120090] Neuron. 1994 Jun;12(6):1269-79 [8011337] Neuron. 1994 Aug;13(2):363-75 [8060617] Curr Biol. 1994 Mar 1;4(3):220-33 [7922327] Eur J Cell Biol. 1995 Mar;66(3):246-56 [7774610] J Neurosci. 1995 Jun;15(6):4328-42 [7540672] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8328-32 [7667289] Neuron. 1995 Sep;15(3):663-73 [7546745] J Neurosci. 1995 Dec;15(12):8246-58 [8613758] J Cell Biol. 1996 Jan;132(1-2):167-79 [8567721] J Biol Chem. 1996 Mar 29;271(13):7694-9 [8631808] Neuron. 1996 Mar;16(3):481-6 [8785046] J Cell Biol. 1996 Jun;133(6):1237-50 [8682861] J Biol Chem. 1996 Aug 23;271(34):20227-30 [8702751] Q Rev Biophys. 1995 Nov;28(4):423-72 [8771234] J Physiol. 1996 Jul 15;494 ( Pt 2):539-53 [8842011] Neuron. 1996 Dec;17(6):1035-7 [8982152] Neuron. 1996 Dec;17(6):1049-55 [8982154] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):997-1001 [9023371] Biochemistry. 1997 Mar 18;36(11):3061-7 [9115981] Science. 1997 Apr 11;276(5310):259-63 [9092476] Nature. 1997 Jul 31;388(6641):478-82 [9242407] Cell. 1997 Aug 8;90(3):523-35 [9267032] J Neurosci. 1997 Oct 1;17(19):7190-202 [9295365] Adv Pharmacol. 1998;42:253-7 [9327892] J Cell Biol. 1997 Nov 17;139(4):885-94 [9362507] Neuron. 1997 Nov;19(5):1087-94 [9390521] J Neurosci. 1998 Jan 1;18(1):81-92 [9412488] Science. 1998 Feb 20;279(5354):1203-6 [9469810] Nature. 1998 Apr 2;392(6675):497-501 [9548254] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7163-8 [9618556] Curr Biol. 1998 Jun 18;8(13):740-9 [9651678] Nature. 1998 Aug 6;394(6693):581-5 [9707119] Neuron. 1998 Sep;21(3):607-16 [9768846] J Neurosci. 1998 Dec 15;18(24):10241-9 [9852561] Nat Neurosci. 1998 Jul;1(3):192-200 [10195143] Nat Neurosci. 1998 Nov;1(7):551-6 [10196561] J Neurosci. 1982 Aug;2(8):1052-61 [7050310] J Cell Biol. 1990 Feb;110(2):449-59 [1967610] Neuron. 1990 Nov;5(5):723-33 [2223095] Science. 1992 Jan 10;255(5041):200-3 [1553547] J Cell Biol. 1992 May;117(4):849-61 [1577861] J Neurochem. 1992 Dec;59(6):2148-57 [1359016] J Cell Biol. 1973 May;57(2):315-44 [4348786] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates. AN - 69340287; 10585413 AB - Diphosphoinositol polyphosphate phosphohydrolase (DIPP) hydrolyzes diadenosine 5',5"'-P(1),P(6)-hexaphosphate (Ap(6)A), a Nudix (nucleoside diphosphate attached-moiety "x") substrate, and two non-Nudix compounds: diphosphoinositol pentakisphosphate (PP-InsP(5)) and bis-diphosphoinositol tetrakisphosphate ((PP)(2)-InsP(4)). Guided by multiple sequence alignments, we used site-directed mutagenesis to obtain new information concerning catalytically essential amino acid residues in DIPP. Mutagenesis of either of two conserved glutamate residues (Glu(66) and Glu(70)) within the Nudt (Nudix-type) catalytic motif impaired hydrolysis of Ap(6)A, PP-InsP(5), and (PP)(2)-InsP(4) >95%; thus, all three substrates are hydrolyzed at the same active site. Two Gly-rich domains (glycine-rich regions 1 and 2 (GR1 and GR2)) flank the Nudt motif with potential sites for cation coordination and substrate binding. GR1 comprises a GGG tripeptide, while GR2 is identified as a new functional motif (GX(2)GX(6)G) that is conserved in yeast homologues of DIPP. Mutagenesis of any of these Gly residues in GR1 and GR2 reduced catalytic activity toward all three substrates by up to 95%. More distal to the Nudt motif, H91L and F84Y mutations substantially decreased the rate of Ap(6)A and (PP)(2)-InsP(4) metabolism (by 71 and 96%), yet PP-InsP(5) hydrolysis was only mildly reduced (by 30%); these results indicate substrate-specific roles for His(91) and Phe(84). This new information helps define DIPP's structural, functional, and evolutionary relationships to Nudix hydrolases. JF - The Journal of biological chemistry AU - Yang, X AU - Safrany, S T AU - Shears, S B AD - Inositide Signaling Group, Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. yang3@niehs.nih.gov Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 35434 EP - 35440 VL - 274 IS - 50 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Dinucleoside Phosphates KW - Inositol Phosphates KW - Recombinant Proteins KW - diadenosine 5',5''''-P1,P6-hexaphosphate KW - 56983-23-4 KW - Acid Anhydride Hydrolases KW - EC 3.6.- KW - diphosphoinositol polyphosphate phosphohydrolase KW - EC 3.6.1.- KW - Index Medicus KW - Humans KW - Circular Dichroism KW - Amino Acid Sequence KW - Saccharomyces cerevisiae -- enzymology KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- isolation & purification KW - Sequence Alignment KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Schizosaccharomyces -- enzymology KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Protein Conformation KW - Inositol Phosphates -- metabolism KW - Acid Anhydride Hydrolases -- chemistry KW - Acid Anhydride Hydrolases -- metabolism KW - Dinucleoside Phosphates -- metabolism KW - Acid Anhydride Hydrolases -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69340287?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-directed+mutagenesis+of+diphosphoinositol+polyphosphate+phosphohydrolase%2C+a+dual+specificity+NUDT+enzyme+that+attacks+diadenosine+polyphosphates+and+diphosphoinositol+polyphosphates.&rft.au=Yang%2C+X%3BSafrany%2C+S+T%3BShears%2C+S+B&rft.aulast=Yang&rft.aufirst=X&rft.date=1999-12-10&rft.volume=274&rft.issue=50&rft.spage=35434&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-13 N1 - Date created - 2000-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Expression and function of the gonadotropin-releasing hormone receptor are dependent on a conserved apolar amino acid in the third intracellular loop. AN - 69335404; 10585457 AB - The coupling of agonist-activated heptahelical receptors to their cognate G proteins is often dependent on the amino-terminal region of the third intracellular loop. Like many G protein-coupled receptors, the gonadotropin-releasing hormone (GnRH) receptor contains an apolar amino acid in this region at a constant distance from conserved Pro and Tyr/Asn residues in the fifth transmembrane domain (TM V). An analysis of the role of this conserved residue (Leu(237)) in GnRH receptor function revealed that the binding affinities of the L237I and L237V mutant receptors were unchanged, but their abilities to mediate GnRH-induced inositol phosphate signaling, G protein coupling, and agonist-induced internalization were significantly impaired. Receptor expression at the cell surface was reduced by replacement of Leu(237) with Val, and abolished by replacement with Ala, Arg, or Asp residues. These results are consistent with molecular modeling of the TM V and VI regions of the GnRH receptor, which predicts that Leu(237) is caged by several apolar amino acids (Ile(233), Ile(234), and Val(240) in TM V, and Leu(262), Leu(265), and Val(269) in TM VI) to form a tight hydrophobic cluster. These findings indicate that the conserved apolar residue (Leu(237)) in the third intracellular loop is an important determinant of GnRH receptor expression and activation, and possibly that of other G protein-coupled receptors. JF - The Journal of biological chemistry AU - Chung, H O AU - Yang, Q AU - Catt, K J AU - Arora, K K AD - Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 35756 EP - 35762 VL - 274 IS - 50 SN - 0021-9258, 0021-9258 KW - Iodine Radioisotopes KW - 0 KW - Receptors, LHRH KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Tyrosine KW - 42HK56048U KW - Asparagine KW - 7006-34-0 KW - Proline KW - 9DLQ4CIU6V KW - Leucine KW - GMW67QNF9C KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - COS Cells KW - Models, Molecular KW - Asparagine -- analysis KW - Amino Acid Sequence KW - Mice KW - Radioligand Assay KW - Proline -- analysis KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Tyrosine -- analysis KW - Mutagenesis, Site-Directed KW - Gonadotropin-Releasing Hormone -- metabolism KW - Conserved Sequence KW - Transfection KW - Kinetics KW - Amino Acid Substitution KW - Receptors, LHRH -- chemistry KW - Receptors, LHRH -- genetics KW - Receptors, LHRH -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69335404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Cloning+and+characterization+of+the+promoter+region+of+human+telomerase+reverse+transcriptase+gene.&rft.au=Horikawa%2C+I%3BCable%2C+P+L%3BAfshari%2C+C%3BBarrett%2C+J+C&rft.aulast=Horikawa&rft.aufirst=I&rft.date=1999-02-15&rft.volume=59&rft.issue=4&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-13 N1 - Date created - 2000-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA and RNA-based vaccines: principles, progress and prospects AN - 17469629; 4659655 AB - DNA vaccines were introduced less than a decade ago but have already been applied to a wide range of infectious and malignant diseases. Here we review the current understanding of the mechanisms underlying the activities of these new vaccines. We focus on recent strategies designed to enhance their function including the use of immunostimulatory (CpG) sequences, dendritic cells (DC), co-stimulatory molecules and cytokine- and chemokine-adjuvants. Although genetic vaccines have been significantly improved, they may not be sufficiently immunogenic for the therapeutic vaccination of patients with infectious diseases or cancer in clinical trials. One promising approach aimed at dramatically increasing the immunogenicity of genetic vaccines involves making them `self-replicating'. This can be accomplished by using a gene encoding RNA replicase, a polyprotein derived from alphaviruses, such as Sindbis virus. Replicase-containing RNA vectors are significantly more immunogenic than conventional plasmids, immunizing mice at doses as low as 0.1 mu g of nucleic acid injected once intramuscularly. Cells transfected with `self-replicating' vectors briefly produce large amounts of antigen before undergoing apoptotic death. This death is a likely result of requisite double-stranded (ds) RNA intermediates, which also have been shown to super-activate DC. Thus, the enhanced immunogenicity of `self-replicating' genetic vaccines may be a result of the production of pro-inflammatory dsRNA, which mimics an RNA-virus infection of host cells. JF - Vaccine AU - Leitner, W W AU - Ying, H AU - Restifo, N P AD - National Cancer Institute, National Institutes of Health, Building 10, Bethesda, MD 20892-1502, USA, restifo@nih.gov Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 765 EP - 777 VL - 18 IS - 9-10 SN - 0264-410X, 0264-410X KW - immunology KW - DNA vaccines KW - RNA vaccines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Reviews KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17469629?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=DNA+and+RNA-based+vaccines%3A+principles%2C+progress+and+prospects&rft.au=Leitner%2C+W+W%3BYing%2C+H%3BRestifo%2C+N+P&rft.aulast=Leitner&rft.aufirst=W&rft.date=1999-12-10&rft.volume=18&rft.issue=9-10&rft.spage=765&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccines; Reviews ER - TY - JOUR T1 - An aerosol challenge mouse model for Moraxella catarrhalis AN - 17459878; 4659660 AB - A simple, reproducible, and non-invasive mouse pulmonary clearance model for Moraxella catarrhalis via aerosol challenge was established. All of eight tested strains could be inoculated into mice at more than 10 super(5) colony-forming units (CFU)/lung with a challenge concentration of 1 x 10 super(9)-6 x 10 super(9) CFU/ml in a nebulizer. The number of bacteria retained at 6 h postchallenge was more than 10 super(4) CFU/lung while at 24 h postchallenge, approximate 10 super(3) CFU/ml or less remained in the lungs. A maximum of 100 mice could be challenged per aerosol exposure. The number of bacteria inoculated in the lungs could be adjusted by the bacterial challenge concentration, the exposure time, and the negative pressure. Lung tissue sections revealed that bacteria were evenly distributed in the lungs. Passive immunization significantly enhanced pulmonary clearance of the homologous strain in this model. These data indicate that this model will be useful for evaluating M. catarrhalis vaccine candidates and studying roles of immunity against M. catarrhalis. JF - Vaccine AU - Hu, W-G AU - Chen, J AU - Collins, F M AU - Gu, X-X AD - Laboratory of Immunology, National Institute on Deafness and Other Communication Disorders, NIH, 5 Research Court, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 799 EP - 804 VL - 18 IS - 9-10 SN - 0264-410X, 0264-410X KW - mice KW - immunology KW - Moraxella catarrhalis KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Aerosols KW - Lung KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17459878?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=An+aerosol+challenge+mouse+model+for+Moraxella+catarrhalis&rft.au=Hu%2C+W-G%3BChen%2C+J%3BCollins%2C+F+M%3BGu%2C+X-X&rft.aulast=Hu&rft.aufirst=W-G&rft.date=1999-12-10&rft.volume=18&rft.issue=9-10&rft.spage=799&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Moraxella catarrhalis; Aerosols; Lung; Vaccines ER - TY - JOUR T1 - Antitransferrin receptor antibody-RNase fusion protein expressed in the mammary gland of transgenic mice AN - 17442025; 4656061 AB - Antibodies fused to human enzymes offer an alternative to specifically targeting tumors with antibodies linked to plant or bacterial toxins. Since large amounts of these reagents can be administered without eliciting non-specific toxicities, efficient methods of production are needed. The goal of this work was to express a complex immunoenzyme fusion protein (immunotoxin) in the mammary gland of transgenic mice. A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang). It was expressed in the mammary gland of mice and secreted into mouse milk. Expression levels in milk were approximately 0.8 g /l. The chimeric protein retained antibody binding activity and protein synthesis inhibitory activity equivalent to that of free Ang. It was specifically cytotoxic to human tumor cells in vitro. JF - Journal of Immunological Methods AU - Newton, D L AU - Pollock, D AU - DiTullio, P AU - Echelard, Y AU - Harvey, M AU - Wilburn, B AU - Williams, J AU - Hoogenboom, H R AU - Raus, JCM AU - Meade, H M AU - Rybak, S M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center Frederick, MD USA Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 159 EP - 167 PB - Elsevier VL - 231 IS - 1-2 SN - 0022-1759, 0022-1759 KW - transgenic mice KW - man KW - immunology KW - antitransferrin receptors KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Antibodies KW - Mammary gland KW - Fusion protein KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17442025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brandweek&rft.atitle=Building+strong+brands&rft.au=Aaker%2C+David+A&rft.aulast=Aaker&rft.aufirst=David&rft.date=1995-10-02&rft.volume=36&rft.issue=37&rft.spage=28&rft.isbn=&rft.btitle=&rft.title=Brandweek&rft.issn=10644318&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mammary gland; Fusion protein; Antibodies DO - http://dx.doi.org/10.1016/S0022-1759(99)00154-4 ER - TY - JOUR T1 - Analysis of cloned Fvs from a phage display library indicates that DNA immunization can mimic antibody response generated by cell immunizations AN - 17441968; 4656055 AB - Generation and cloning of antibodies against cell surface antigens can be simplified by combining DNA immunization which enables generation of antibodies against a protein in its natural configuration without the need for any protein purification step and antibody phage display which due to its immense screening power and physical coupling between the phenotype and genotype of antibodies simplifies the cloning of antibody genes. Since DNA immunization is expected to elicit antibodies against a protein in its natural configuration, we wanted to see if it can mimic the antibody response generated by cell immunization. A phage display library made from splenic mRNA of a mouse immunized with mesothelin cDNA was panned on mesothelin-positive cells. The single-chain Fvs (scFvs) selected were then analyzed. We obtained several anti-mesothelin scFvs. One of these Fvs is almost identical to the Fv of a monoclonal antibody that was previously obtained from a hybridoma in which the mice were immunized with a mesothelin-positive ovarian cancer cell line. Another Fv was found to be specific for mesothelin present on human cells. Our results indicate that an antibody phage display library made from spleens of DNA-immunized mice is a rapid and efficient alternative to cell immunization for obtaining antibodies against different epitopes of a membrane antigen that is very difficult to purify in a native form. JF - Journal of Immunological Methods AU - Chowdhury, P S AU - Pastan, I AD - National Institutes of Health, National Cancer Institute, Laboratory of Molecular Biology, Building 37, Room 4B20, 37 Convent Road, MSC-4255 Bethesda, MD 20892 USA Y1 - 1999/12/10/ PY - 1999 DA - 1999 Dec 10 SP - 83 EP - 91 PB - Elsevier VL - 231 IS - 1-2 SN - 0022-1759, 0022-1759 KW - mice KW - immunology KW - DNA vaccines KW - Fv KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Spleen KW - Vaccines KW - Antibody response KW - W3 33375:Antibodies KW - F 06807:Active immunization KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17441968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Analysis+of+cloned+Fvs+from+a+phage+display+library+indicates+that+DNA+immunization+can+mimic+antibody+response+generated+by+cell+immunizations&rft.au=Chowdhury%2C+P+S%3BPastan%2C+I&rft.aulast=Chowdhury&rft.aufirst=P&rft.date=1999-12-10&rft.volume=231&rft.issue=1-2&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/10.1016%2FS0022-1759%2899%2900142-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antibody response; Vaccines; Spleen DO - http://dx.doi.org/10.1016/S0022-1759(99)00142-8 ER - TY - JOUR T1 - Inhibition of Cell Death in Human Mammary Epithelial Cells by the Cooked Meat-Derived Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine AN - 17420972; 4646390 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet in cooked meat. To examine if PhIP and its reactive metabolite N-hydroxy-PhIP inhibit apoptosis in human mammary epithelial MCF-10A cells, confluent cultures deprived of serum and growth factors were incubated for 24 h with either compound. The percentages of dead cells (mean plus or minus SEM, n = 3) as measured by trypan blue exclusion were 5.7 plus or minus 0.6, 3.4 plus or minus 0.3, 2.7 plus or minus 0.3, and 0.2 plus or minus 0.003%, in control, 1 mu M N-hydroxy-PhIP-, 5 mu M N-hydroxy-PhIP-, and 100 mu M PhIP-treated dishes, respectively. The expression of Bcl-2 and Bcl-x sub(L) as quantitated by Western blotting was 1.2- to 1.9-fold higher in the treated groups. PhIP-DNA adducts induced by N-hydroxy-PhIP in MCF-10A cells measured by the super(32)P-postlabeling assay were low (<1 x 10 super(7), relative adduct labeling). No adducts were detected after incubation with PhIP. Western blot analysis indicated that PhIP increased ERK2 phosphorylation concomitant with Bcl-2. The results suggest that the inhibition of cell death in mammary epithelial cells by PhIP occurs independently of PhIP-DNA adducts and may involve enhanced signaling through the MAP kinase pathways. JF - Biochemical and Biophysical Research Communications AU - Venugopal, M AU - Agarwal, R AU - Callaway, A AU - Schut, HA AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Building 37, Room 3C28, 37 Convent Drive MSC 4255, Bethesda, 20892-4255, Maryland, elizabeth_snyderwine@nih.gov Y1 - 1999/12/09/ PY - 1999 DA - 1999 Dec 09 SP - 203 EP - 207 PB - Academic Press VL - 266 IS - 1 SN - 0006-291X, 0006-291X KW - man KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - Toxicology Abstracts KW - Meat KW - Apoptosis KW - Mammary gland KW - Food KW - Cooking KW - Epithelium KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17420972?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+Biophysical+Research+Communications&rft.atitle=Inhibition+of+Cell+Death+in+Human+Mammary+Epithelial+Cells+by+the+Cooked+Meat-Derived+Carcinogen+2-Amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine&rft.au=Venugopal%2C+M%3BAgarwal%2C+R%3BCallaway%2C+A%3BSchut%2C+HA%3BSnyderwine%2C+E+G&rft.aulast=Venugopal&rft.aufirst=M&rft.date=1999-12-09&rft.volume=266&rft.issue=1&rft.spage=203&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+Biophysical+Research+Communications&rft.issn=0006291X&rft_id=info:doi/10.1006%2Fbbrc.1999.1801 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cooking; Food; Meat; Mammary gland; Epithelium; Apoptosis DO - http://dx.doi.org/10.1006/bbrc.1999.1801 ER - TY - JOUR T1 - Withdrawal of IL-7 induces Bax translocation from cytosol to mitochondria through a rise in intracellular pH. AN - 69341758; 10588730 AB - IL-7 functions as a trophic factor during T lymphocyte development by a mechanism that is partly based on the induction of Bcl-2, which protects cells from apoptosis. Here we report a mechanism by which cytokine withdrawal activates the prodeath protein Bax. On loss of IL-7 in a dependent cell line, Bax protein translocated from the cytosol to the mitochondria, where it integrated into the mitochondrial membrane. This translocation was attributable to a conformational change in the Bax protein itself. We show that a rise in intracellular pH preceded mitochondrial translocation and triggered the change in Bax conformation. Intracellular pH in the IL-7-dependent cells rose steadily to peak over pH 7.8 by 6 hr after cytokine withdrawal, paralleling the time point of Bax translocation (a similar alkalinization and Bax translocation was also observed after IL-3 withdrawal from a dependent cell line). The conformation of Bax was directly altered by pH of 7.8 or higher and was demonstrated by increased protease sensitivity, exposure of N terminus epitopes, and exposure of a hydrophobic domain in the C terminus. Eliminating charged amino acids at the C or N termini of Bax induced a conformational change similar to that induced by raising pH, implicating these residues in the pH effect. Therefore, we have shown that by either cytokine withdrawal, experimental manipulation of pH, or site-directed mutagenesis, Bax protein changes conformation, exposing membrane-seeking domains, thereby inducing mitochondrial translocation and initiating the cascade of events leading to apoptotic death. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Khaled, A R AU - Kim, K AU - Hofmeister, R AU - Muegge, K AU - Durum, S K AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1999/12/07/ PY - 1999 DA - 1999 Dec 07 SP - 14476 EP - 14481 VL - 96 IS - 25 SN - 0027-8424, 0027-8424 KW - Bax protein, mouse KW - 0 KW - Interleukin-7 KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - bcl-2-Associated X Protein KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Apoptosis KW - Hydrogen-Ion Concentration KW - Biological Transport KW - Mice KW - Cell Line KW - Protein Conformation KW - Cytosol -- metabolism KW - Proto-Oncogene Proteins -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Interleukin-7 -- physiology KW - Mitochondria -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69341758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Withdrawal+of+IL-7+induces+Bax+translocation+from+cytosol+to+mitochondria+through+a+rise+in+intracellular+pH.&rft.au=Khaled%2C+A+R%3BKim%2C+K%3BHofmeister%2C+R%3BMuegge%2C+K%3BDurum%2C+S+K&rft.aulast=Khaled&rft.aufirst=A&rft.date=1999-12-07&rft.volume=96&rft.issue=25&rft.spage=14476&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-05 N1 - Date created - 2000-01-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Gen Physiol. 1988 Oct;92(4):489-507 [2849630] Cytokine Growth Factor Rev. 1999 Mar;10(1):41-60 [10379911] J Immunol. 1989 Aug 15;143(4):1215-22 [2787360] Methods Enzymol. 1994;228:182-93 [8047007] J Exp Med. 1994 Nov 1;180(5):1955-60 [7964471] J Biol Chem. 1995 Feb 17;270(7):3203-11 [7852405] J Exp Med. 1995 Apr 1;181(4):1519-26 [7699333] Science. 1995 Oct 6;270(5233):96-9 [7569956] Biochim Biophys Acta. 1995 Nov 9;1269(2):122-8 [7488644] J Biotechnol. 1996 May 15;46(3):187-95 [8672290] J Immunol. 1996 Aug 1;157(3):1107-16 [8757615] J Cell Biol. 1997 Dec 1;139(5):1281-92 [9382873] Curr Opin Immunol. 1998 Apr;10(2):196-207 [9602309] J Immunol. 1998 Jun 15;160(12):5735-41 [9637482] Methods Mol Biol. 1998;88:23-33 [9664295] EMBO J. 1998 Jul 15;17(14):3878-85 [9670005] Radiat Res. 1998 Aug;150(2):183-9 [9692363] Cell. 1998 Aug 21;94(4):491-501 [9727492] J Exp Med. 1998 Sep 21;188(6):1125-33 [9743531] Oncogene. 1998 Sep 3;17(9):1069-78 [9764817] Eur J Biochem. 1996 Sep 1;240(2):461-7 [8841413] J Immunol. 1996 Dec 15;157(12):5315-23 [8955178] J Cell Sci. 1997 Mar;110 ( Pt 5):653-61 [9092947] J Biol Chem. 1997 May 23;272(21):13829-34 [9153240] Cell. 1997 Jun 27;89(7):1033-41 [9215626] Science. 1997 Jul 18;277(5324):370-2 [9219694] Nat Genet. 1997 Aug;16(4):358-63 [9241272] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11357-62 [9326614] Science. 1997 Oct 24;278(5338):687-9 [9381178] J Cell Biol. 1998 Oct 5;143(1):207-15 [9763432] J Cell Biol. 1998 Oct 5;143(1):217-24 [9763433] J Cell Biol. 1999 Mar 8;144(5):891-901 [10085289] EMBO J. 1999 May 4;18(9):2330-41 [10228148] Comment In: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):529-31 [10639111] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The steroid hormone dehydroepiandrosterone inhibits CYP1A1 expression in vitro by a post-transcriptional mechanism. AN - 69308611; 10575002 AB - The adrenal steroid hormone dehydroepiandrosterone (DHEA) is a potent inhibitor of mammary carcinogenesis induced by polycyclic aromatic hydrocarbons (PAH), though its mechanism is unclear. We examined the effect of DHEA on the expression of the carcinogen-activating enzyme cytochrome P450 1A1 (CYP1A1) in MCF-7 human breast epithelial carcinoma cells. DHEA inhibited the increase in CYP1A1 enzyme activity that occurs when MCF-7 cells are exposed to the PAH dimethylbenzanthracene (DMBA) or 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). However, DHEA did not directly inhibit enzyme activity as it had no effect when added to the cells after induction by DMBA or TCDD. We observed that the increase of CYP1A1 mRNA in MCF-7 cells caused by DMBA or TCDD was inhibited by DHEA in a concentration-dependent manner. However, DHEA did not inhibit CYP1A1 promoter-driven transcription, indicating that it did not affect the aryl hydrocarbon receptor, which regulates transcription of the CYP1A1 gene. Actinomycin D chase experiments showed that DHEA caused a time- and concentration-dependent decrease in CYP1A1 mRNA levels, indicating that DHEA inhibits CYP1A1 expression by decreasing CYP1A1 mRNA stability. These data demonstrate that DHEA inhibits PAH-induced CYP1A1 mRNA expression and enzyme activity in vitro by a post-transcriptional mechanism. This regulation of the expression of carcinogen-activating enzymes may be responsible for the chemopreventive activity of DHEA and may be one of its physiologic functions in vivo. JF - The Journal of biological chemistry AU - Ciolino, H P AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Division of Basic Sciences, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1999/12/03/ PY - 1999 DA - 1999 Dec 03 SP - 35186 EP - 35190 VL - 274 IS - 49 SN - 0021-9258, 0021-9258 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Dehydroepiandrosterone KW - 459AG36T1B KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Dehydroepiandrosterone Sulfate KW - 57B09Q7FJR KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Carcinogens -- pharmacology KW - Dose-Response Relationship, Drug KW - Humans KW - Polychlorinated Dibenzodioxins -- pharmacology KW - RNA, Messenger -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Dehydroepiandrosterone Sulfate -- pharmacology KW - RNA, Messenger -- metabolism KW - Transfection KW - Neoplasms -- prevention & control KW - Time Factors KW - Cytochrome P-450 CYP1A1 -- genetics KW - Cytochrome P-450 CYP1A1 -- metabolism KW - RNA Processing, Post-Transcriptional -- drug effects KW - Dehydroepiandrosterone -- pharmacology KW - Cytochrome P-450 CYP1A1 -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69308611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+steroid+hormone+dehydroepiandrosterone+inhibits+CYP1A1+expression+in+vitro+by+a+post-transcriptional+mechanism.&rft.au=Ciolino%2C+H+P%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1999-12-03&rft.volume=274&rft.issue=49&rft.spage=35186&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-03 N1 - Date created - 2000-02-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transcriptional repression of the transforming growth factor-beta type I receptor gene by DNA methylation results in the development of TGF-beta resistance in human gastric cancer. AN - 69362143; 10602482 AB - The transforming growth factor-beta (TGF-beta) signaling pathway subserves an essential tumor suppressor function in various cell types. A heteromeric complex composed of TGF-beta type I (RI) and type II (RII) receptors is required for TGF-beta signaling. We have identified a subset of human gastric cancer cell lines which are insensitive to TGF-beta and which express a low level of TGF-beta type I receptor mRNA relative to a gastric cancer cell line which is highly responsive to TGF-beta. Using these cells, we show that hypermethylation of a CpG island in the 5' region of the TGF-beta RI gene provides another potentially important mechanism of escape from negative growth control by TGF-beta. This hypermethylation was found in four of five human gastric cancer cell lines and five out of 40 (12.5%) primary tumors examined. In human gastric cancer cell lines, treatment with the demethylating agent, 5-aza-2'-deoxycytidine, resulted in increased expression of the TGF-beta RI gene, but not the RII gene. Transient transfection of an RI expression vector into the TGF-beta resistant SNU-601 cell line restores TGF-beta responsiveness. These findings suggest that one of the mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve aberrant methylation of CpG islands in the 5' region of the TGF-beta RI gene. JF - Oncogene AU - Kang, S H AU - Bang, Y J AU - Im, Y H AU - Yang, H K AU - Lee, D A AU - Lee, H Y AU - Lee, H S AU - Kim, N K AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland, MD 20892-5055, USA. Y1 - 1999/12/02/ PY - 1999 DA - 1999 Dec 02 SP - 7280 EP - 7286 VL - 18 IS - 51 SN - 0950-9232, 0950-9232 KW - DNA, Neoplasm KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Index Medicus KW - Transforming Growth Factor beta -- pharmacology KW - Tumor Cells, Cultured KW - Humans KW - DNA, Neoplasm -- genetics KW - Transcription, Genetic KW - Transforming Growth Factor beta -- metabolism KW - Transcriptional Activation KW - Gene Expression Regulation, Neoplastic KW - Receptors, Transforming Growth Factor beta -- genetics KW - Stomach Neoplasms -- metabolism KW - DNA Methylation KW - Stomach Neoplasms -- genetics KW - Drug Resistance, Neoplasm -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69362143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Transcriptional+repression+of+the+transforming+growth+factor-beta+type+I+receptor+gene+by+DNA+methylation+results+in+the+development+of+TGF-beta+resistance+in+human+gastric+cancer.&rft.au=Kang%2C+S+H%3BBang%2C+Y+J%3BIm%2C+Y+H%3BYang%2C+H+K%3BLee%2C+D+A%3BLee%2C+H+Y%3BLee%2C+H+S%3BKim%2C+N+K%3BKim%2C+S+J&rft.aulast=Kang&rft.aufirst=S&rft.date=1999-12-02&rft.volume=18&rft.issue=51&rft.spage=7280&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxygenated analogues of 1-[2-(Diphenylmethoxy)ethyl]- and 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as potential extended-action cocaine-abuse therapeutic agents. AN - 69338575; 10585212 AB - An investigation into the preparation of potential extended-release cocaine-abuse therapeutic agents afforded a series of compounds related to 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine (1a) and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (1b) (GBR 12935 and GBR 12909, respectively), which were designed, synthesized, and evaluated for their ability to bind to the dopamine transporter (DAT) and to inhibit the uptake of [(3)H]-labeled dopamine (DA). The addition of hydroxy and methoxy substituents to the benzene ring on the phenylpropyl moiety of 1a-1d resulted in a series of potent and selective ligands for the DAT (analogues 5-28). The hydroxyl groups were included to incorporate a medium-chain carboxylic acid ester into the molecules, to form oil-soluble prodrugs, amenable to "depot" injection techniques. The introduction of an oxygen-containing functionality to the propyl side chain provided ketones 29 and 30, which demonstrated greatly reduced affinity for the DAT and decreased potency in inhibiting the uptake of [(3)H]DA, and benzylic alcohols 31-36, which were highly potent and selective at binding to the DAT and inhibiting [(3)H]DA uptake. The enantiomers of 32 (34 and 36) were practically identical in biological testing. Compounds 1b, 32, 34, and 36 all demonstrated the ability to decrease cocaine-maintained responding in monkeys without affecting behaviors maintained by food, with 34 and 36 equipotent to each other and both more potent in behavioral tests than the parent compound 1b. Intramuscular injections of compound 41 (the decanoate ester of racemate 32) eliminated cocaine-maintained behavior for about a month following one single injection, without affecting food-maintained behavior. The identification of analogues 32, 34, and 36, thus, provides three potential candidates for esterification and formulation as extended-release cocaine-abuse therapeutic agents. JF - Journal of medicinal chemistry AU - Lewis, D B AU - Matecka, D AU - Zhang, Y AU - Hsin, L W AU - Dersch, C M AU - Stafford, D AU - Glowa, J R AU - Rothman, R B AU - Rice, K C AD - Laboratory of Medicinal Chemistry, Building 8, Room B1-23, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12/02/ PY - 1999 DA - 1999 Dec 02 SP - 5029 EP - 5042 VL - 42 IS - 24 SN - 0022-2623, 0022-2623 KW - 1-(2-(bis(4--fluorophenyl)methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl)piperazine decanoate KW - 0 KW - 1-(2-(bis(4-fluorophenyl)--methoxy)ethyl)-4-(3-hydroxy-3-phenylpropyl)piperazine KW - Carrier Proteins KW - Delayed-Action Preparations KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Ligands KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Piperazines KW - Slc6a3 protein, rat KW - Tritium KW - 10028-17-8 KW - vanoxerine KW - 90X28IKH43 KW - 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine KW - 9J9974WIBA KW - Oxygen KW - S88TT14065 KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Molecular Structure KW - Animals KW - Carrier Proteins -- metabolism KW - Dopamine -- metabolism KW - Structure-Activity Relationship KW - Hydroxylation KW - Rats KW - Oxygen -- chemistry KW - Macaca mulatta KW - Methylation KW - Male KW - Piperazines -- chemical synthesis KW - Piperazines -- chemistry KW - Dopamine Uptake Inhibitors -- chemical synthesis KW - Cocaine-Related Disorders -- drug therapy KW - Piperazines -- pharmacology KW - Piperazines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69338575?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Oxygenated+analogues+of+1-%5B2-%28Diphenylmethoxy%29ethyl%5D-+and+1-%5B2-%5BBis%284-fluorophenyl%29methoxy%5Dethyl%5D-4-%283-phenylpropyl%29piperazines+%28GBR+12935+and+GBR+12909%29+as+potential+extended-action+cocaine-abuse+therapeutic+agents.&rft.au=Lewis%2C+D+B%3BMatecka%2C+D%3BZhang%2C+Y%3BHsin%2C+L+W%3BDersch%2C+C+M%3BStafford%2C+D%3BGlowa%2C+J+R%3BRothman%2C+R+B%3BRice%2C+K+C&rft.aulast=Lewis&rft.aufirst=D&rft.date=1999-12-02&rft.volume=42&rft.issue=24&rft.spage=5029&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preliminary results of the Annual Survey of Deaf and Hard of Hearing Children and Youth in Puerto Rico: the first wave. AN - 85311893; pmid-10734694 AB - Preliminary findings are provided from the data collected in Puerto Rico through the Annual Survey of Deaf and Hard of Hearing Children and Youth during the 1997-1998 school year. The study was conducted as a part of an initiative to increase participation in the Annual Survey among the deaf and hard of hearing school-age population in Puerto Rico. Demographic, instructional, etiological, audiological, and communication data on 336 deaf and hard of hearing school age children were collected and summarized. The findings suggest the existence of a heterogeneous deaf community rather than the traditionally conceived homogeneous community. The discussion emphasizes the description of those attributes that suggest heterogeneity and the urgent need to continue to collect the kind of data gathered in the survey. The authors urge that Puerto Rican educators and researchers be stimulated to address the educational and health-related needs of Puerto Rico's deaf and hard of hearing school-age population. JF - American annals of the deaf AU - Albertorio, J R AU - Holden-Pitt, L AU - Rawlings, B AD - National Institute on Deafness and Other Communication Disorders-Office of Research on Minority Health (NICDC-ORMH), Bethesda, MD, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 386 EP - 394 VL - 144 IS - 5 SN - 0002-726X, 0002-726X KW - Index Medicus KW - National Library of Medicine KW - Teaching -- statistics & numerical data KW - Education, Special -- statistics & numerical data KW - Hispanic Americans KW - Humans KW - Child KW - Adolescent KW - Puerto Rico -- epidemiology KW - Child, Preschool KW - Deafness -- epidemiology KW - Questionnaires KW - Hearing Impaired Persons KW - Deafness -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85311893?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+annals+of+the+deaf&rft.atitle=Preliminary+results+of+the+Annual+Survey+of+Deaf+and+Hard+of+Hearing+Children+and+Youth+in+Puerto+Rico%3A+the+first+wave.&rft.au=Albertorio%2C+J+R%3BHolden-Pitt%2C+L%3BRawlings%2C+B&rft.aulast=Albertorio&rft.aufirst=J&rft.date=1999-12-01&rft.volume=144&rft.issue=5&rft.spage=386&rft.isbn=&rft.btitle=&rft.title=American+annals+of+the+deaf&rft.issn=0002726X&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Exploring spatial patterns of mortality: the new atlas of United States mortality. AN - 85278808; pmid-10602146 AB - The National Center for Health Statistics, CDC, has produced an Atlas of United States Mortality which includes maps of rates for the leading causes of death in the United States for the period 1988-1992. As part of this project, many aspects of statistical mapping have been re-examined to maximize the atlas's effectiveness in conveying accurate mortality patterns to epidemiologists and public health practitioners. Because recent cognitive research demonstrated that no one map style is optimal for answering many different map questions, maps and graphs of several different mortality statistics are included for each cause of death. New mixed effects models were developed to provide predicted rates and improved variance estimates. Results from these models were smoothed using a weighted head-banging algorithm to produce maps of general spatial trends free of background noise. Maps of White female lung cancer rates from the new atlas are presented here to illustrate how this innovative combination of maps and graphs permits greater exploration of the underlying mortality data than is possible from previous single-map atlas designs. Published in 1999 by John Wiley & Sons, Ltd. This article is a U.S. Government work and is in the public domain in the United States. JF - Statistics in Medicine AU - Pickle, L W AU - Mungiole, M AU - Jones, G K AU - White, A A AD - NCI/DCCPS, 6130 Executive Boulevard, MSC 7344, EPN Rm. 313, Bethesda, MD 20892, USA. PY - 1999 SP - 3211 EP - 3220 VL - 18 IS - 23 SN - 0277-6715, 0277-6715 KW - Whites KW - United States KW - Lung Neoplasms KW - Centers for Disease Control and Prevention (U.S.) KW - Human KW - Adult KW - Algorithms KW - Middle Age KW - Aged KW - Female KW - Small-Area Analysis KW - Mortality KW - Public Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85278808?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Statistics+in+Medicine&rft.atitle=Exploring+spatial+patterns+of+mortality%3A+the+new+atlas+of+United+States+mortality.&rft.au=Pickle%2C+L+W%3BMungiole%2C+M%3BJones%2C+G+K%3BWhite%2C+A+A&rft.aulast=Pickle&rft.aufirst=L&rft.date=1999-12-01&rft.volume=18&rft.issue=23&rft.spage=3211&rft.isbn=&rft.btitle=&rft.title=Statistics+in+Medicine&rft.issn=02776715&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Never again joy without sorrow: the effect on parents of a child with ataxia-telangiectasia. AN - 85275885; pmid-10594880 AB - The purpose of this study was to explore the impact of having a child with ataxia-telangiectasia (A-T) as well as to assess parental understanding of the genetics of A-T and attitudes toward carrier testing. Sixty-eight parents of individuals with A-T were interviewed. Ninety percent of the parents correctly believed if there is a child with A-T, both are obligate heterozygotes. Only 9% knew each well sib had a two-thirds chance of being a carrier. Eighty-four percent would have their unaffected child tested for carrier status prior to age 18 years. Eighty-two percent believed heterozygosity is associated with increased health risks. We offer the following recommendations. 1) Physicians must realize that communicating the possibility of early death is difficult; parents need guidelines so they know what to expect, but diagnosis should not be a death sentence. Clinicians should stress individual variations in expression of the disorder and offer hope for future progress in treatment. 2) Parents underestimated carrier risks for the well sib and the frequency of carrier status in the general population. Although these distortions are self-protective, they interfere with transmission of accurate genetic information to their children. Parents should be referred to genetic counseling. 3) Psychological counseling should be offered to families at the time of diagnosis so parents can support each other, the affected, and unaffected offspring. JF - American Journal of Medical Genetics AU - Fanos, J H AU - Mackintosh, M A AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. PY - 1999 SP - 413 EP - 419 VL - 87 IS - 5 SN - 0148-7299, 0148-7299 KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Aged KW - Parent-Child Relations KW - Child KW - Child, Preschool KW - Aged, 80 and over KW - Adult KW - Support, Non-U.S. Gov't KW - Middle Age KW - Ataxia Telangiectasia KW - Adolescent KW - Family Health KW - Male KW - Female KW - Heterozygote KW - Genetic Counseling KW - Patient Education UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85275885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Never+again+joy+without+sorrow%3A+the+effect+on+parents+of+a+child+with+ataxia-telangiectasia.&rft.au=Fanos%2C+J+H%3BMackintosh%2C+M+A&rft.aulast=Fanos&rft.aufirst=J&rft.date=1999-12-01&rft.volume=87&rft.issue=5&rft.spage=413&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Chronic effects of xanthines on levels of central receptors in mice. AN - 69988908; 10456233 AB - 1. Chronic ingestion of caffeine causes a significant increase in levels of A1-adenosine, nicotinic and muscarinic receptors, serotonergic receptors, GABAA receptors and L-type calcium channels in cerebral cortical membranes from mice NIH Swiss strain mice. 2. Chronic theophylline and paraxanthine had effects similar to those of caffeine except that levels of L-type channels were unchanged. Chronic theobromine, a weak adenosine antagonist, and 1-isobutyl-3-methylxanthine (IBMX), a potent adenosine antagonist and phosphodiesterase inhibitor, caused only an increase in levels of A1-adenosine receptors. A combination of chronic caffeine and IBMX had the same effects on receptors as caffeine alone. Chronic 3,7-dimethyl-1-propargylxanthine (DMPX), a somewhat selective A2A-antagonist, caused only an increase in levels of A1-adenosine receptors. Pentoxifylline, an adenosine-uptake inhibitor inactive at adenosine receptors, had no effect on receptor levels or calcium channels. 3. A comparison of plasma and brain levels of xanthines indicated that caffeine penetrated more readily and attained somewhat higher brain levels than theophylline or theobromine. Penetration and levels were even lower for IBMX, paraxanthine, DMPX, and pentoxyfylline. 4. The results suggest that effective blockade of both A1 and A2A-adenosine receptors is necessary for the full spectrum of biochemical changes elicited by chronic ingestion of xanthines, such as caffeine, theophylline, and paraxanthine. JF - Cellular and molecular neurobiology AU - Shi, D AU - Daly, J W AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 719 EP - 732 VL - 19 IS - 6 SN - 0272-4340, 0272-4340 KW - Calcium Channels KW - 0 KW - Central Nervous System Stimulants KW - Nerve Tissue Proteins KW - Receptors, Cholinergic KW - Receptors, Drug KW - Receptors, GABA KW - Receptors, Purinergic P1 KW - Receptors, Serotonin KW - Xanthines KW - Caffeine KW - 3G6A5W338E KW - 3,7-dimethyl-1-propargylxanthine KW - 5YFR5SPS6T KW - Theophylline KW - C137DTR5RG KW - Theobromine KW - OBD445WZ5P KW - 1,7-dimethylxanthine KW - Q3565Y41V7 KW - Pentoxifylline KW - SD6QCT3TSU KW - 1-Methyl-3-isobutylxanthine KW - TBT296U68M KW - Index Medicus KW - Receptors, Serotonin -- drug effects KW - Receptors, GABA -- drug effects KW - Animals KW - Pentoxifylline -- pharmacology KW - Cerebral Cortex -- drug effects KW - Drug Interactions KW - Brain Chemistry KW - Caffeine -- pharmacology KW - Theobromine -- pharmacology KW - Mice KW - Radioligand Assay KW - Pentoxifylline -- pharmacokinetics KW - 1-Methyl-3-isobutylxanthine -- pharmacokinetics KW - Caffeine -- pharmacokinetics KW - Receptors, Purinergic P1 -- drug effects KW - Receptors, Cholinergic -- drug effects KW - Theophylline -- pharmacology KW - Calcium Channels -- drug effects KW - Theophylline -- pharmacokinetics KW - Corpus Striatum -- drug effects KW - 1-Methyl-3-isobutylxanthine -- pharmacology KW - Theobromine -- pharmacokinetics KW - Male KW - Theobromine -- analogs & derivatives KW - Receptors, Drug -- genetics KW - Receptors, Drug -- biosynthesis KW - Central Nervous System Stimulants -- pharmacology KW - Nerve Tissue Proteins -- biosynthesis KW - Gene Expression Regulation -- drug effects KW - Nerve Tissue Proteins -- genetics KW - Xanthines -- pharmacology KW - Central Nervous System Stimulants -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69988908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Chronic+effects+of+xanthines+on+levels+of+central+receptors+in+mice.&rft.au=Shi%2C+D%3BDaly%2C+J+W&rft.aulast=Shi&rft.aufirst=D&rft.date=1999-12-01&rft.volume=19&rft.issue=6&rft.spage=719&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolation and purification of phosphate dependent glutaminase from sarcoma-180 tumor and its antineoplastic effects on murine model system. AN - 69463641; 10746973 AB - High rate of glutamine use is a characteristic of tumor cell both in vivo and in vitro and experimental cancer therapies have developed by depriving tumor cells of glutamine. In several investigations, bacterial glutaminase was found to be a potent therapeutic agent against varieties of tumor, but it showed suppressive effects on haematopoietic systems and inhibitory effects on normal lymphocytic blastogenesis. No antineoplastic study has nevertheless been undertaken with glutaminase enzyme purified from mammalian source. In the present study we report the purification of glutaminase enzyme from mitochondria of highly malignant S-180 cell using ion exchange chromatography and affinity column chromatography of glutamine. Purified enzyme is a kidney type phosphate dependent glutaminase with Mr 64 KD. Effect of enzyme therapy has been investigated in transplantable as well as induced tumor model in both ascites and solid form. It has been observed that the enzyme at the total dose of 10 unit/mouse successfully inhibited the tumor burden both in ascitic and solid tumor and subsequently increases the host's life span. There was no significant toxic effect on the peripheral blood cells. JF - Journal of experimental & clinical cancer research : CR AU - Maity, P AU - Chakraborty, S AU - Bhattacharya, P AU - Sarkar, R AD - Dept. of Metabolic Regulation, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 475 EP - 480 VL - 18 IS - 4 SN - 0392-9078, 0392-9078 KW - Antineoplastic Agents KW - 0 KW - Glutaminase KW - EC 3.5.1.2 KW - Index Medicus KW - Chromatography, Affinity KW - Mice, Inbred Strains KW - Animals KW - Mitochondria -- enzymology KW - Mice KW - Chromatography, Ion Exchange KW - Ultracentrifugation KW - Male KW - Glutaminase -- isolation & purification KW - Sarcoma 180 -- enzymology KW - Sarcoma 180 -- drug therapy KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Antineoplastic Agents -- isolation & purification KW - Glutaminase -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69463641?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.atitle=Isolation+and+purification+of+phosphate+dependent+glutaminase+from+sarcoma-180+tumor+and+its+antineoplastic+effects+on+murine+model+system.&rft.au=Maity%2C+P%3BChakraborty%2C+S%3BBhattacharya%2C+P%3BSarkar%2C+R&rft.aulast=Maity&rft.aufirst=P&rft.date=1999-12-01&rft.volume=18&rft.issue=4&rft.spage=475&rft.isbn=&rft.btitle=&rft.title=Journal+of+experimental+%26+clinical+cancer+research+%3A+CR&rft.issn=03929078&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-15 N1 - Date created - 2000-05-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer chemoprevention: progress and promise. AN - 69450258; 10711244 AB - Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. The focus of chemoprevention research in the next millennium will include defining the genotypic and phenotypic (functional and histological) changes during carcinogenesis, the cancer risk conferred by these changes, their modulation in preclinical experimentation and randomised clinical trials by chemopreventive drugs, dietary agents and regimens and treatments resulting from early detection. The key elements of this research effort will be basic and translational risk evaluation programmes; chemopreventive and dietary agent drug discovery and development; development of transgenic animal models; required safety and pharmacology studies; well-designed phase I, II and III chemoprevention studies; and much expanded early detection programmes. The large number of chemoprevention research programmes now ongoing ensures that the promise of chemoprevention will continue to be realised in the next decade. JF - European journal of cancer (Oxford, England : 1990) AU - Kelloff, G J AU - Sigman, C C AU - Greenwald, P AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 20892, USA. kelloffg@dcpcepn.nci.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 2031 EP - 2038 VL - 35 IS - 14 SN - 0959-8049, 0959-8049 KW - Anticarcinogenic Agents KW - 0 KW - Antineoplastic Agents KW - Biomarkers, Tumor KW - Index Medicus KW - Public Health KW - Anticarcinogenic Agents -- therapeutic use KW - Risk Factors KW - Humans KW - Biomarkers, Tumor -- analysis KW - Quality of Life KW - Health Education KW - Drug Design KW - Risk Assessment KW - Neoplasms -- drug therapy KW - Neoplasms -- prevention & control KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69450258?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Cancer+chemoprevention%3A+progress+and+promise.&rft.au=Kelloff%2C+G+J%3BSigman%2C+C+C%3BGreenwald%2C+P&rft.aulast=Kelloff&rft.aufirst=G&rft.date=1999-12-01&rft.volume=35&rft.issue=14&rft.spage=2031&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-23 N1 - Date created - 2000-03-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain. AN - 69441352; 10693972 AB - Single Na+ channel currents were recorded from cell-attached membrane patches from two neuronal cell lines derived from rat brain, B50 and B104, and compared before and after exposure of the cells to purified brevetoxin, PbTx-3. B50 and B104 Na+ channels usually exhibited fast activation and inactivation as is typical of TTX-sensitive Na+ channels. PbTx-3 modified channel gating in both cell lines. PbTx-3 caused (1) significant increases in the frequency of channel reopening, indicating a slowing of channel inactivation, (2) a change in the voltage dependence of the channels, promoting channel opening during steady-state voltage clamp of the membrane at voltages throughout the activation range of Na+ currents, but notably near the resting potential of these cells (-60 - -50 mV), and (3) a significant, 6.7 mV hyperpolarized shift in the threshold potential for channel opening. Na+ channel slope conductance did not change in PbTx-3-exposed B50 and B104 neurons. These effects of Pbx-3 may cause hyperexcitability as well as inhibitory effects in intact brain. JF - Neurotoxicology AU - Purkerson, S L AU - Baden, D G AU - Fieber, L A AD - University of Miami Rosenstiel School of Marine and Atmospheric Science, Division of Marine Biology and Fisheries, NIEHS Marine and Freshwater Biomedical Sciences Center, FL 33149, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 909 EP - 920 VL - 20 IS - 6 SN - 0161-813X, 0161-813X KW - Marine Toxins KW - 0 KW - Oxocins KW - Sodium Channels KW - brevetoxin KW - 98225-48-0 KW - Index Medicus KW - Rats KW - Animals KW - Patch-Clamp Techniques KW - Time Factors KW - Cell Line KW - Neurons -- metabolism KW - Sodium Channels -- metabolism KW - Brain -- metabolism KW - Marine Toxins -- toxicity KW - Ion Channel Gating -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69441352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Characterization+of+the+dose-response+of+CYP1B1%2C+CYP1A1%2C+and+CYP1A2+in+the+liver+of+female+Sprague-Dawley+rats+following+chronic+exposure+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin.&rft.au=Walker%2C+N+J%3BPortier%2C+C+J%3BLax%2C+S+F%3BCrofts%2C+F+G%3BLi%2C+Y%3BLucier%2C+G+W%3BSutter%2C+T+R&rft.aulast=Walker&rft.aufirst=N&rft.date=1999-02-01&rft.volume=154&rft.issue=3&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-22 N1 - Date created - 2000-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weighing the consequence of doing nothing versus those of doing something: post-exposure chemoprophylaxis for occupational exposures to HIV. AN - 69424832; 10658784 JF - The Journal of hospital infection AU - Henderson, D K AD - Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, 20892-1504, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - S225 EP - S233 VL - 43 Suppl SN - 0195-6701, 0195-6701 KW - Anti-HIV Agents KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Infectious Disease Transmission, Vertical -- prevention & control KW - Animals KW - Humans KW - Disease Models, Animal KW - Occupational Exposure KW - Anti-HIV Agents -- therapeutic use KW - Occupational Diseases -- prevention & control KW - HIV Infections -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69424832?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+hospital+infection&rft.atitle=Weighing+the+consequence+of+doing+nothing+versus+those+of+doing+something%3A+post-exposure+chemoprophylaxis+for+occupational+exposures+to+HIV.&rft.au=Henderson%2C+D+K&rft.aulast=Henderson&rft.aufirst=D&rft.date=1999-12-01&rft.volume=43+Suppl&rft.issue=&rft.spage=S225&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+hospital+infection&rft.issn=01956701&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-24 N1 - Date created - 2000-02-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A randomized EPOCH vs. CHOP front-line therapy for aggressive non-Hodgkin's lymphoma patients: long-term results. AN - 69408485; 10643541 AB - The value of continuous-infusion chemotherapy (EPOCH) vs. the standard CHOP combination was evaluated in 78 patients with previously untreated aggressive non-Hodgkin's lymphoma in a randomized phase III clinical trial. The EPOCH regimen given to 38 patients consisted of the drugs etoposide (50 mg/m2), vincristine (0.4 mg/m2), and doxorubicin (10 mg/m2), all given in a continuous infusion on days 1-4. Cyclophosphamide (750 mg/m2) was administered on day 6 as i.v. bolus, while prednisone was given orally 60 mg/m2 on days 1-6. Courses were repeated every three weeks. CHOP was given to 40 patients as routinely prescribed. Forty-eight patients were males and thirty were females. Their ages ranged from 19-75 years (median 45 years). Forty-three (55%) had grade 2 and thirty-five (45%) had grade 3 pathologic subtype. Nine patients (12%) presented with stage I, fourteen (18%) with stage II, forty (51%) with stage III, and fifteen (19%) with stage IV disease. The different clinico-pathologic characteristics, including international index categories, were comparable in the two groups. The number of courses given ranged between 3 and 9 (median 6) for both the EPOCH and CHOP regimens. Complete remission (CR) was achieved in 19 (50%), and 27 (67%) of the 38 and 40 patients for both the EPOCH and CHOP combinations, respectively. After a median observation time of 27 months, the four-year overall and failure-free survival rates were 42% and 30% for the EPOCH and 71% and 54% for the CHOP regimen (P = 0.006 and 0.1 for the overall and FFS rates, respectively). Toxicities were comparable and were mostly of grades 1 and 2, except for hair loss, hematologic toxicities, and infectious episodes which were more common in the EPOCH group. In the EPOCH group, overall survival rates were 55% vs. 22% (P 2 factors) groups, respectively. Thus, it may be concluded that continuous-infusion (EPOCH) chemotherapy did not improve treatment outcome over that of the CHOP regimen for aggressive non-Hodgkin's lymphoma patients. JF - Annals of oncology : official journal of the European Society for Medical Oncology AU - Khaled, H M AU - Zekri, Z K AU - Mokhtar, N AU - Ali, N M AU - Darwish, T AU - Elattar, I AU - Gaafar, R AU - Moawad, M S AD - Department of Medical Oncology, National Cancer Institute, Cairo, Egypt. khaled@brainyl.ie-eg.com Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1489 EP - 1492 VL - 10 IS - 12 SN - 0923-7534, 0923-7534 KW - Vincristine KW - 5J49Q6B70F KW - Etoposide KW - 6PLQ3CP4P3 KW - Doxorubicin KW - 80168379AG KW - Cyclophosphamide KW - 8N3DW7272P KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Etoposide -- administration & dosage KW - Humans KW - Adult KW - Vincristine -- administration & dosage KW - Aged KW - Middle Aged KW - Doxorubicin -- administration & dosage KW - Prednisone -- administration & dosage KW - Male KW - Female KW - Survival Analysis KW - Lymphoma, Non-Hodgkin -- drug therapy KW - Lymphoma, Large B-Cell, Diffuse -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69408485?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.atitle=A+randomized+EPOCH+vs.+CHOP+front-line+therapy+for+aggressive+non-Hodgkin%27s+lymphoma+patients%3A+long-term+results.&rft.au=Khaled%2C+H+M%3BZekri%2C+Z+K%3BMokhtar%2C+N%3BAli%2C+N+M%3BDarwish%2C+T%3BElattar%2C+I%3BGaafar%2C+R%3BMoawad%2C+M+S&rft.aulast=Khaled&rft.aufirst=H&rft.date=1999-12-01&rft.volume=10&rft.issue=12&rft.spage=1489&rft.isbn=&rft.btitle=&rft.title=Annals+of+oncology+%3A+official+journal+of+the+European+Society+for+Medical+Oncology&rft.issn=09237534&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-02 N1 - Date created - 2000-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate. AN - 69398486; 10630567 AB - Cadmium is a known human carcinogen based on findings of lung cancer in exposed populations. A more controversial target site for cadmium is the human prostate gland, for which some studies indicate a link between cadmium exposure and cancer. Our work in various strains of Wistar rats has shown that cadmium can induce tumors in the ventral lobe of the prostate. The relevance of this type of lesion to human prostate cancer has been questioned because the ventral lobe of the rat prostate, unlike the dorsolateral lobe, has no embryological homolog in the human gland. In this study we investigated the chronic toxic and carcinogenic effects of cadmium in the Noble (NBL/Cr) rat, with particular attention to lesions of the prostate. Cadmium chloride (CdCl2) was given as a single sc injection (0, 1, 2, 4, 8, 16, or 32 micromol/kg) to groups (initially n = 30) of 10-week-old rats. Rats were observed for up to 72 weeks following exposure. In rats that were injected with the lower doses of cadmium ( or =8 micromol/kg) the proliferative-lesion response in the dorsolateral prostate gradually declined to near control levels (8 micromol/kg = 63%; 16 micromol/kg = 60%; 32 micromol/kg = 52%). The loss of prostatic response at the higher doses of cadmium was probably due to loss of testicular function secondary to cadmium treatment. This was reflected in a very high incidence (>90%) of lesions, indicative of testicular hypofunction, including tubular degeneration, mineralization, and interstitial (Leydig) cell tumors, at doses in excess of 16 micromol/kg. Malignant injection-site sarcomas occurred at the two highest doses of cadmium, while pituitary adenomas were elevated by cadmium exposure at the highest dose. These results show that cadmium induces proliferative lesions in the dorsolateral prostate of the Noble rat, a model having a presumed relevance to human prostate cancers. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Waalkes, M P AU - Anver, M AU - Diwan, B A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. waalkes@niehs.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 154 EP - 161 VL - 52 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Hyperplasia -- pathology KW - Animals KW - Hyperplasia -- chemically induced KW - Calcinosis -- pathology KW - Sarcoma, Experimental -- chemically induced KW - Body Weight -- drug effects KW - Rats, Wistar KW - Injections, Subcutaneous KW - Cell Division -- drug effects KW - Calcinosis -- chemically induced KW - Sarcoma, Experimental -- pathology KW - Male KW - Pituitary Neoplasms -- chemically induced KW - Carcinogens -- administration & dosage KW - Cadmium -- administration & dosage KW - Prostatic Hyperplasia -- chemically induced KW - Pituitary Neoplasms -- pathology KW - Testicular Neoplasms -- pathology KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Prostatic Hyperplasia -- pathology KW - Testicular Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69398486?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Carcinogenic+effects+of+cadmium+in+the+noble+%28NBL%2FCr%29+rat%3A+induction+of+pituitary%2C+testicular%2C+and+injection+site+tumors+and+intraepithelial+proliferative+lesions+of+the+dorsolateral+prostate.&rft.au=Waalkes%2C+M+P%3BAnver%2C+M%3BDiwan%2C+B+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1999-12-01&rft.volume=52&rft.issue=2&rft.spage=154&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-10 N1 - Date created - 2000-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The redox pathway of S-nitrosoglutathione, glutathione and nitric oxide in cell to neuron communications. AN - 69398034; 10630687 AB - Recent results demonstrated that S-nitrosoglutathione (GSNO) and nitric oxide (*NO) protect brain dopamine neurons from hydroxyl radical (*OH)-induced oxidative stress in vivo because they are potent antioxidants. GSNO and *NO terminate oxidant stress in the brain by (i) inhibiting iron-stimulated hydroxyl radicals formation or the Fenton reaction, (ii) terminating lipid peroxidation, (iii) augmenting the antioxidative potency of glutathione (GSH), (iv) mediating neuroprotective action of brain-derived neurotrophin (BDNF), and (v) inhibiting cysteinyl proteases. In fact, GSNO--S-nitrosylated GSH--is approximately 100 times more potent than the classical antioxidant GSH. In addition, S-nitrosylation of cysteine residues by GSNO inactivates caspase-3 and HIV-1 protease, and prevents apoptosis and neurotoxicity. GSNO-induced antiplatelet aggregation is also mediated by S-nitrosylation of clotting factor XIII. Thus the elucidation of chemical reactions involved in this GSNO pathway (GSH GS* + *NO-->[GSNO]-->GSSG + *NO-->GSH) is necessary for understanding the biology of *NO, especially its beneficial antioxidative and neuroprotective effects in the CNS. GSNO is most likely generated in the endothelial and astroglial cells during oxidative stress because these cells contain mM GSH and nitric oxide synthase. Furthermore, the transfer of GSH and *NO to neurons via this GSNO pathway may facilitate cell to neuron communications, including not only the activation of guanylyl cyclase, but also the nitrosylation of iron complexes, iron containing enzymes, and cysteinyl proteases. GSNO annihilates free radicals and promotes neuroprotection via its c-GMP-independent nitrosylation actions. This putative pathway of GSNO/GSH/*NO may provide new molecular insights for the redox cycling of GSH and GSSG in the CNS. JF - Free radical research AU - Chiueh, C C AU - Rauhala, P AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1264, USA. chiueh@helix.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 641 EP - 650 VL - 31 IS - 6 SN - 1071-5762, 1071-5762 KW - Antioxidants KW - 0 KW - HIV Protease Inhibitors KW - Nitroso Compounds KW - Nitric Oxide KW - 31C4KY9ESH KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Caspases KW - EC 3.4.22.- KW - HIV Protease KW - EC 3.4.23.- KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Astrocytes -- cytology KW - Endothelium -- metabolism KW - Enzyme Activation KW - Humans KW - Mice KW - Brain -- metabolism KW - Lipid Peroxidation KW - Caspases -- metabolism KW - Endothelium -- cytology KW - Oxidation-Reduction KW - Antioxidants -- metabolism KW - HIV Protease -- metabolism KW - Astrocytes -- metabolism KW - HIV Protease Inhibitors -- metabolism KW - Neurons -- metabolism KW - Nitroso Compounds -- metabolism KW - Glutathione -- metabolism KW - Nitroso Compounds -- chemistry KW - Neurons -- cytology KW - Nitric Oxide -- metabolism KW - Glutathione -- chemistry KW - Cell Communication -- physiology KW - Nitric Oxide -- chemistry KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69398034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Risk+of+leukemia+after+platinum-based+chemotherapy+for+ovarian+cancer.&rft.au=Travis%2C+L+B%3BHolowaty%2C+E+J%3BBergfeldt%2C+K%3BLynch%2C+C+F%3BKohler%2C+B+A%3BWiklund%2C+T%3BCurtis%2C+R+E%3BHall%2C+P%3BAndersson%2C+M%3BPukkala%2C+E%3BSturgeon%2C+J%3BStovall%2C+M&rft.aulast=Travis&rft.aufirst=L&rft.date=1999-02-01&rft.volume=340&rft.issue=5&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-03 N1 - Date created - 2000-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hemoglobin and iron-evoked oxidative stress in the brain: protection by bile pigments, manganese and S-nitrosoglutathione. AN - 69397021; 10630686 AB - In the present in vitro and in vivo study we investigated the pro-oxidant effects of hemoglobin, as well as the antioxidant effects of its metabolites, in the brain. Incubation of rat brain homogenates with hemoglobin (0-10 microM) but not hemin induced lipid peroxidation up to 24 h (EC50 = 1.2 microM). Hemoglobin's effects were similar to ferrous ion (EC50 = 1.7 microM) and were blocked by the chelating agent deferoxamine (IC50 0.5 microM) and a nitric oxide-releasing compound S-nitrosoglutathione (IC50 = 40 microM). However, metabolites of hemoglobin - biliverdin and bilirubin - inhibited brain lipid peroxidation induced by cell disruption and hemoglobin (biliverdin IC50 = 12-30 and bilirubin IC50 = 75-170 microM). Biliverdin's antioxidative effects in spontaneous and iron-evoked lipid peroxidation were further augmented by manganese (2 microM) since manganese is an antioxidative transition metal and conjugates with bile pigments. Intrastriatal infusion of hemoglobin (0-24 nmol) produced slight, but significant 20-22% decreases in striatal dopamine levels. Whereas, intrastriatal infusion of ferrous citrate (0-24 nmol) dose-dependently induced a greater 66% depletion of striatal dopamine which was preceded by an acute increase of lipid peroxidation. In conclusion, contrary to the in vitro results hemoglobin is far less neurotoxic than ferrous ions in the brain. It is speculated that hemoglobin may be partially detoxified by heme oxygenase and biliverdin reductase to its antioxidative metabolites in the brain. However, in head trauma and stroke, massive bleeding could significantly produce iron-mediated oxidative stress and neurodegeneration which could be minimized by endogenous antioxidants such as biliverdin, bilirubin, manganese and S-nitrosoglutathione. JF - Free radical research AU - Van Bergen, P AU - Rauhala, P AU - Spooner, C M AU - Chiueh, C C AD - Unit on Neurodegeneration and Neuroprotection, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1264, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 631 EP - 640 VL - 31 IS - 6 SN - 1071-5762, 1071-5762 KW - Antioxidants KW - 0 KW - Bile Pigments KW - Ferrous Compounds KW - Hemoglobins KW - Nitroso Compounds KW - Oxidants KW - Tissue Extracts KW - monoferrous acid citrate KW - 33KM3X4QQW KW - Manganese KW - 42Z2K6ZL8P KW - S-Nitrosoglutathione KW - 57564-91-7 KW - Iron KW - E1UOL152H7 KW - Glutathione KW - GAN16C9B8O KW - Deferoxamine KW - J06Y7MXW4D KW - Biliverdine KW - O9MIA842K9 KW - Bilirubin KW - RFM9X3LJ49 KW - Index Medicus KW - Animals KW - Bilirubin -- pharmacology KW - Lipid Peroxidation -- drug effects KW - Biliverdine -- pharmacology KW - Muscle, Skeletal -- drug effects KW - Rats KW - Rats, Sprague-Dawley KW - Antioxidants -- metabolism KW - Deferoxamine -- pharmacology KW - Bilirubin -- metabolism KW - Ferrous Compounds -- pharmacology KW - Tissue Extracts -- metabolism KW - Oxidants -- metabolism KW - Biliverdine -- metabolism KW - Muscle, Skeletal -- metabolism KW - Male KW - Manganese -- pharmacology KW - Manganese -- metabolism KW - Nitroso Compounds -- metabolism KW - Bile Pigments -- pharmacology KW - Brain -- cytology KW - Brain -- drug effects KW - Glutathione -- metabolism KW - Brain -- metabolism KW - Hemoglobins -- pharmacology KW - Glutathione -- pharmacology KW - Iron -- metabolism KW - Oxidative Stress -- physiology KW - Bile Pigments -- metabolism KW - Hemoglobins -- metabolism KW - Oxidative Stress -- drug effects KW - Nitroso Compounds -- pharmacology KW - Glutathione -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69397021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+research&rft.atitle=Hemoglobin+and+iron-evoked+oxidative+stress+in+the+brain%3A+protection+by+bile+pigments%2C+manganese+and+S-nitrosoglutathione.&rft.au=Van+Bergen%2C+P%3BRauhala%2C+P%3BSpooner%2C+C+M%3BChiueh%2C+C+C&rft.aulast=Van+Bergen&rft.aufirst=P&rft.date=1999-12-01&rft.volume=31&rft.issue=6&rft.spage=631&rft.isbn=&rft.btitle=&rft.title=Free+radical+research&rft.issn=10715762&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-03 N1 - Date created - 2000-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial. AN - 69388869; 10618647 AB - Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis. Copyright 1999 Wiley-Liss, Inc. JF - Journal of cellular biochemistry AU - Bruno, S AU - Torrisi, R AU - Costantini, M AU - Baglietto, L AU - Fontana, V AU - Gatteschi, B AU - Melioli, G AU - Nicolo, G AU - Curotto, A AU - Malcangi, B AU - Bruttini, G P AU - Varaldo, M AU - Bruzzi, P AU - Decensi, A AD - Cytometry Unit, National Cancer Institute, 16132 Genoa, Italy. silviab@anatomiau.unige.it Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 311 EP - 321 VL - 76 IS - 2 SN - 0730-2312, 0730-2312 KW - Antineoplastic Agents KW - 0 KW - Biomarkers, Tumor KW - DNA, Neoplasm KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Biomarkers, Tumor -- genetics KW - Fenretinide -- therapeutic use KW - Neoplasm Recurrence, Local -- chemistry KW - Humans KW - Biomarkers, Tumor -- analysis KW - Flow Cytometry KW - Ploidies KW - Antineoplastic Agents -- therapeutic use KW - Neoplasm Recurrence, Local -- genetics KW - Neoplasm Recurrence, Local -- prevention & control KW - Cell Division KW - Urinary Bladder Neoplasms -- chemistry KW - Urinary Bladder Neoplasms -- genetics KW - Urinary Bladder Neoplasms -- drug therapy KW - DNA, Neoplasm -- genetics KW - DNA, Neoplasm -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69388869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Assessment+of+DNA+flow+cytometry+as+a+surrogate+end+point+biomarker+in+a+bladder+cancer+chemoprevention+trial.&rft.au=Bruno%2C+S%3BTorrisi%2C+R%3BCostantini%2C+M%3BBaglietto%2C+L%3BFontana%2C+V%3BGatteschi%2C+B%3BMelioli%2C+G%3BNicolo%2C+G%3BCurotto%2C+A%3BMalcangi%2C+B%3BBruttini%2C+G+P%3BVaraldo%2C+M%3BBruzzi%2C+P%3BDecensi%2C+A&rft.aulast=Bruno&rft.aufirst=S&rft.date=1999-12-01&rft.volume=76&rft.issue=2&rft.spage=311&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-14 N1 - Date created - 2000-02-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TGF-beta signaling from receptors to the nucleus. AN - 69384574; 10611754 AB - In the past three years, a novel signal transduction pathway downstream of the transforming growth factor-beta (TGF-beta) superfamily receptor serine-threonine kinases has been shown to be mediated by a family of latent transcription factors called 'Smads'. These proteins mediate a short-circuited pathway in which a set of receptor-activated Smads are phosphorylated directly by the receptor kinase and then translocate to the nucleus complexed to the common mediator, Smad4, to participate in transcriptional complexes. Smads 2 and 3 mediate signals predominantly from the TGF-beta receptors. Of these, specific roles have been ascribed to Smad3 in control of chemotaxis of neutrophils and macrophages and the inhibition of Smad3 activity by the oncogene Evi-1 suggests that it may play a role in leukemogenesis. Other data, such as the induction by the inflammatory cytokine interferon-gamma of an inhibitory Smad, Smad7, which blocks the actions of Smad3, suggest that identification of the specific gene targets of Smad proteins in immune cells will provide new insight into the mechanisms of TGF-beta action on these cells. JF - Microbes and infection AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute Building 41, Room C629, 41 Library Drive, MSC 5055, Bethesda, MD 20892-5055, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1265 EP - 1273 VL - 1 IS - 15 SN - 1286-4579, 1286-4579 KW - Receptors, Transforming Growth Factor beta KW - 0 KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Trans-Activators -- genetics KW - Humans KW - Receptors, Transforming Growth Factor beta -- genetics KW - Cell Nucleus -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Transforming Growth Factor beta -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69384574?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbes+and+infection&rft.atitle=TGF-beta+signaling+from+receptors+to+the+nucleus.&rft.au=Roberts%2C+A+B&rft.aulast=Roberts&rft.aufirst=A&rft.date=1999-12-01&rft.volume=1&rft.issue=15&rft.spage=1265&rft.isbn=&rft.btitle=&rft.title=Microbes+and+infection&rft.issn=12864579&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-23 N1 - Date created - 2000-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction to the special issue: treatment process in DATOS. AN - 69383974; 10617093 AB - Several important findings from the drug abuse treatment outcome studies (DATOS) are presented in this issue of drug and alcohol dependence. These studies focus on the drug abuse treatment process in areas of engagement in treatment and participation in program activities, the effect of the patient's age and treatment history in predicting treatment retention and outcomes, and the impact of prior treatment experience on the level of treatment engagement and subsequent outcomes. A cost-benefit model for drug abuse treatment is developed. Significant contributions are made in the development of a comprehensive model of the treatment process, including the relationship of patient attributes, program factors, and outcomes. Findings on retention from the United Kingdom's national treatment outcome research study (NTORS), a study similar in design to DATOS, also are presented. JF - Drug and alcohol dependence AU - Fletcher, B W AU - Battjes, R J AD - Division of Clinical and Services Research, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA. www.datos.org. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 81 EP - 87 VL - 57 IS - 2 SN - 0376-8716, 0376-8716 KW - Index Medicus KW - Cost-Benefit Analysis -- economics KW - Age Factors KW - Humans KW - Treatment Outcome KW - Substance-Related Disorders -- economics KW - Substance-Related Disorders -- rehabilitation KW - Substance-Related Disorders -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69383974?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Finasteride%2C+a+5alpha-reductase+inhibitor%2C+blocks+the+anticonvulsant+activity+of+progesterone+in+mice.&rft.au=Kokate%2C+T+G%3BBanks%2C+M+K%3BMagee%2C+T%3BYamaguchi%2C+S%3BRogawski%2C+M+A&rft.aulast=Kokate&rft.aufirst=T&rft.date=1999-02-01&rft.volume=288&rft.issue=2&rft.spage=679&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-31 N1 - Date created - 2000-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Misclassification in case-control studies of gene-environment interactions: assessment of bias and sample size. AN - 69383757; 10613335 AB - In studies of gene-environment interactions, exposure misclassification can lead to bias in the estimation of an interaction effect and increased sample size. The magnitude of the bias and the consequent increase in sample size for fixed misclassification probabilities are highly dependent on the prevalence of the misclassified factor and on the interaction model. This paper describes a relatively simple approach to assess the impact of misclassification on bias in the estimation of multiplicative or additive interactions and on sample size requirements. Applications of this method illustrate that even small errors in the assessment of environmental or genetic factors can result in biased interaction parameters and substantially increased sample size requirements that can compromise the feasibility of the study. Also, an example is provided where nondifferential misclassification biases an additive interaction parameter away from the null value, even under conditions where a multiplicative interaction parameter will always be biased toward the null value. Efforts to improve the accuracy in measuring both genetic and environmental factors are critical for the valid assessment of gene-environment interactions in case-control studies. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Garcia-Closas, M AU - Rothman, N AU - Lubin, J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1043 EP - 1050 VL - 8 IS - 12 SN - 1055-9965, 1055-9965 KW - Benzo(a)pyrene KW - 3417WMA06D KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Sensitivity and Specificity KW - Odds Ratio KW - Reproducibility of Results KW - Gene Frequency KW - Humans KW - Glutathione Transferase -- genetics KW - Body Mass Index KW - Breast Neoplasms -- epidemiology KW - Mathematics KW - Genotype KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Risk Factors KW - Breast Neoplasms -- etiology KW - Benzo(a)pyrene -- adverse effects KW - Effect Modifier, Epidemiologic KW - Prevalence KW - Cocarcinogenesis KW - Genetic Predisposition to Disease -- genetics KW - Environmental Exposure -- analysis KW - Neoplasms -- epidemiology KW - Case-Control Studies KW - Sample Size KW - Environmental Exposure -- classification KW - Environmental Exposure -- adverse effects KW - Bias (Epidemiology) KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69383757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Misclassification+in+case-control+studies+of+gene-environment+interactions%3A+assessment+of+bias+and+sample+size.&rft.au=Garcia-Closas%2C+M%3BRothman%2C+N%3BLubin%2C+J&rft.aulast=Garcia-Closas&rft.aufirst=M&rft.date=1999-12-01&rft.volume=8&rft.issue=12&rft.spage=1043&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A staged approach to the treatment of Wegener's granulomatosis: induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. AN - 69381871; 10616016 AB - To determine the efficacy of a daily cyclophosphamide (CYC) and glucocorticoid induction and methotrexate (MTX) remission-maintenance regimen for the treatment of Wegener's granulomatosis (WG). An open-label, prospective, standardized trial for the treatment of WG was performed using CYC and glucocorticoids for remission induction and MTX for remission maintenance. Thirty-one patients were enrolled in this study. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance resulted in disease remission for all 31 patients. The median time to remission was 3 months and the median time to discontinuation of glucocorticoids was 8 months. No patients have died, and 5 patients (16%) have had disease relapses at a median of 13 months after achieving remission. Only 2 patients (6%) have had to withdraw from the trial as a result of medication toxicity. The use of CYC and glucocorticoids for remission induction and MTX for remission maintenance was shown by this study to be an acceptable alternative therapy for patients with active WG, including those with severe disease at onset. JF - Arthritis and rheumatism AU - Langford, C A AU - Talar-Williams, C AU - Barron, K S AU - Sneller, M C AD - Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 2666 EP - 2673 VL - 42 IS - 12 SN - 0004-3591, 0004-3591 KW - Glucocorticoids KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Methotrexate KW - YL5FZ2Y5U1 KW - Abridged Index Medicus KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Methotrexate -- pharmacology KW - Humans KW - Aged KW - Child KW - Glucocorticoids -- pharmacology KW - Adult KW - Middle Aged KW - Adolescent KW - Secondary Prevention KW - Female KW - Male KW - Remission Induction KW - Granulomatosis with Polyangiitis -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69381871?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Arthritis+and+rheumatism&rft.atitle=A+staged+approach+to+the+treatment+of+Wegener%27s+granulomatosis%3A+induction+of+remission+with+glucocorticoids+and+daily+cyclophosphamide+switching+to+methotrexate+for+remission+maintenance.&rft.au=Langford%2C+C+A%3BTalar-Williams%2C+C%3BBarron%2C+K+S%3BSneller%2C+M+C&rft.aulast=Langford&rft.aufirst=C&rft.date=1999-12-01&rft.volume=42&rft.issue=12&rft.spage=2666&rft.isbn=&rft.btitle=&rft.title=Arthritis+and+rheumatism&rft.issn=00043591&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-28 N1 - Date created - 2000-01-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Salivary gland cancer in the United States. AN - 69376329; 10613342 AB - The risk of salivary gland cancer (SGC) is increased in atomic bomb survivors and after radiotherapy, but other risk factors are not well established. Some studies have suggested an association of SGC with breast cancer and with exposure to various viruses or UVB radiation. Corroborating evidence of these associations was sought by using population-based registries to examine the demographic distribution of SGC, patterns of secondary primary cancers after SGC, and risk of SGC with AIDS. SGC incidence per 100,000 persons did not change between 1973 and 1992, averaging 1.2 in males and 0.8 in females, with a steep age gradient. To examine the relationship between UVB exposure and SGC, population-based, age-adjusted incidence rates of SGC were plotted against the UVB insolation of each registry site. Regression analysis suggested no correlation between SGC incidence and increasing UVB insolation (beta = 0.10, R2 = 0.08). SGC also did not appear to be associated with second cancers that have been linked to herpes or papilloma viruses or with AIDS [observed/expected (O/E) ratio, <2.8], but all of these conditions are so uncommon that only very large relative risks would have been statistically significant. Women with SGC before age 35 had a statistically nonsignificant elevation in breast cancer risk [O/E, 3.30; 95% confidence interval (CI), 0.66-9.65], and older women had no increased risk of breast cancer. SGC patients were at increased risk for nonsalivary, second-primary oropharyngeal cancers (O/E, 3.27; 95% CI, 2.00-5.05), thyroid cancer (O/E, 3.31; 95% CI, 1.07-7.73), and lung cancer (O/E, 1.86; 95% CI, 1.45-2.35), particularly in patients whose SGC was treated with radiotherapy (O/E, 2.83; 95% CI, 2.06-3.80). In summary, SGC remains rare and does not appear to be associated with AIDS, virally related malignancies, or UVB. Patients who have had SGC, however, should be monitored for subsequent oropharyngeal, thyroid, and lung cancers. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Sun, E C AU - Curtis, R AU - Melbye, M AU - Goedert, J J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20852, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1095 EP - 1100 VL - 8 IS - 12 SN - 1055-9965, 1055-9965 KW - Radioactive Fallout KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Regression Analysis KW - Neoplasms, Second Primary -- etiology KW - Humans KW - SEER Program KW - Aged KW - Age Distribution KW - Radioactive Fallout -- adverse effects KW - Radiotherapy -- adverse effects KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Neoplasms, Second Primary -- epidemiology KW - Risk Factors KW - Ultraviolet Rays -- adverse effects KW - Incidence KW - United States -- epidemiology KW - Sex Distribution KW - Acquired Immunodeficiency Syndrome -- etiology KW - Female KW - Male KW - Salivary Gland Neoplasms -- etiology KW - Salivary Gland Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69376329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Salivary+gland+cancer+in+the+United+States.&rft.au=Sun%2C+E+C%3BCurtis%2C+R%3BMelbye%2C+M%3BGoedert%2C+J+J&rft.aulast=Sun&rft.aufirst=E&rft.date=1999-12-01&rft.volume=8&rft.issue=12&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of beta-carotene supplementation on serum vitamin D metabolite concentrations. AN - 69375684; 10613346 AB - In the alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) study, a large randomized placebo-controlled trial designed to test the cancer prevention effects of alpha-tocopherol (50 mg/day) and beta-carotene (20 mg/day), participants receiving supplemental beta-carotene had significantly higher rates of lung cancer than those not receiving beta-carotene. It has been hypothesized that the supplemental beta-carotene may have interfered with the synthesis of vitamin D and that the resulting lower concentrations of vitamin D contributed to the elevated cancer incidence. We evaluated whether supplementation with beta-carotene altered the serum concentrations of either 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D in the ATBC Study, by comparing on-study changes between baseline and follow-up serum samples among 20 randomly selected matched pairs of subjects from the beta-carotene and placebo groups. In a matched-pair analysis, the difference between the changes in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the beta-carotene supplement and placebo groups were small and statistically nonsignificant. These results provide no evidence that beta-carotene supplementation interferes with the endogenous production of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and suggest that it is unlikely that an interaction between supplemental beta-carotene and vitamin D metabolites contributed to the modest increase in lung cancer incidence observed in the ATBC Study. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Freedman, D M AU - Tangrea, J A AU - Virtamo, J AU - Albanes, D AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. mf101e@nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1115 EP - 1116 VL - 8 IS - 12 SN - 1055-9965, 1055-9965 KW - Antioxidants KW - 0 KW - Placebos KW - beta Carotene KW - 01YAE03M7J KW - Vitamin D KW - 1406-16-2 KW - 25-hydroxyvitamin D KW - 64719-49-9 KW - 1,25-dihydroxyvitamin D KW - 66772-14-3 KW - Index Medicus KW - Drug Interactions KW - Age Factors KW - Lung Neoplasms -- epidemiology KW - Humans KW - Seasons KW - Incidence KW - Follow-Up Studies KW - Lung Neoplasms -- chemically induced KW - Time Factors KW - Statistics, Nonparametric KW - Matched-Pair Analysis KW - Antioxidants -- adverse effects KW - Vitamin D -- blood KW - Vitamin D -- analogs & derivatives KW - beta Carotene -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69375684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=The+effect+of+beta-carotene+supplementation+on+serum+vitamin+D+metabolite+concentrations.&rft.au=Freedman%2C+D+M%3BTangrea%2C+J+A%3BVirtamo%2C+J%3BAlbanes%2C+D&rft.aulast=Freedman&rft.aufirst=D&rft.date=1999-12-01&rft.volume=8&rft.issue=12&rft.spage=1115&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. AN - 69374935; 10613340 AB - To assess the hypothesis that oral contraceptives (OCs) increase the risk of cervical adenocarcinomas, we conducted a six-center case-control study of 124 patients with adenocarcinomas, 139 with squamous cell carcinomas, and 307 population controls. Women between the ages of 18 and 69 who were newly diagnosed with cervical adenocarcinomas between 1992 and 1996 were eligible. Healthy female controls and a second case group of incident cervical squamous cell carcinomas were matched to the adenocarcinoma cases. All participants were interviewed regarding OCs, other risk factors for cervical carcinoma, and utilization of cytological screening, and a PCR-based test determined HPV genotype of cervical samples for both case groups and controls. Use of OCs was positively and significantly associated with adenocarcinomas and positively but weakly associated with squamous cell carcinomas. Associations between OCs and invasive adenocarcinomas (n = 91), squamous cell carcinoma in situ (n = 48), and invasive squamous cell carcinomas (n = 91) disappeared after accounting for HPV infection, sexual history, and cytological screening, but a positive association remained between current use of OCs and cervical adenocarcinoma in situ (n = 33). This association persisted after stratification by screening and sexual history and after restriction according to HPV status, but small numbers made it difficult to exclude detection bias, selection bias, or residual confounding by HPV as potential explanations Current OC use was associated with cervical adenocarcinomas in situ, but we saw no other evidence that OCs independently increase the risk of cervical carcinomas. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Lacey, J V AU - Brinton, L A AU - Abbas, F M AU - Barnes, W A AU - Gravitt, P E AU - Greenberg, M D AU - Greene, S M AU - Hadjimichael, O C AU - McGowan, L AU - Mortel, R AU - Schwartz, P E AU - Silverberg, S G AU - Hildesheim, A AD - National Cancer Institute, Bethesda, Maryland 20852-7234, USA. laceyj@exchange.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1079 EP - 1085 VL - 8 IS - 12 SN - 1055-9965, 1055-9965 KW - Contraceptives, Oral KW - 0 KW - DNA, Neoplasm KW - Index Medicus KW - Neoplasm Staging KW - Papillomavirus Infections -- complications KW - Humans KW - Papillomaviridae KW - Aged KW - DNA, Neoplasm -- analysis KW - Sexual Behavior KW - Polymerase Chain Reaction KW - Mass Screening KW - Risk Factors KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Middle Aged KW - Adolescent KW - Bias (Epidemiology) KW - Female KW - Tumor Virus Infections -- complications KW - Uterine Cervical Neoplasms -- etiology KW - Contraceptives, Oral -- adverse effects KW - Carcinoma, Squamous Cell -- etiology KW - Adenocarcinoma -- chemically induced KW - Carcinoma, Squamous Cell -- pathology KW - Adenocarcinoma -- etiology KW - Carcinoma, Squamous Cell -- chemically induced KW - Uterine Cervical Neoplasms -- chemically induced KW - Uterine Cervical Neoplasms -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69374935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Cholera+toxin+suppresses+interleukin+%28IL%29-12+production+and+IL-12+receptor+beta1+and+beta2+chain+expression.&rft.au=Braun%2C+M+C%3BHe%2C+J%3BWu%2C+C+Y%3BKelsall%2C+B+L&rft.aulast=Braun&rft.aufirst=M&rft.date=1999-02-01&rft.volume=189&rft.issue=3&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Estimating lung cancer risk with exposure to environmental tobacco smoke. AN - 69370783; 10592146 AB - Estimates of lung cancer in nonsmokers due to exposure to environmental tobacco smoke (ETS) in the workplace or in the home may be developed in several ways. Estimates may be based on (italic)a(/italic)) models developed using the full range of data in smokers; (italic)b(/italic)) models developed using data restricted to smokers with a low smoking rate, for example, (3/4) 10 cigarettes per day; (italic)c(/italic)) models developed using data from studies of residential exposure to ETS of nonsmokers, with exposures based on smoking rates of spouses; and (italic)d(/italic)) models using data from studies of occupational exposure to ETS of nonsmokers. Methods (italic)a(/italic) and (italic)b(/italic) require an estimate of cigarette equivalent exposure for ETS as well as assumptions on the cigarette equivalent dose to target cells from ETS and on the comparability of lung cancer risk per unit dose from smokers and nonsmokers. Summary relative risks (RRs) and 95% confidence intervals (CI) from ETS studies of nonsmokers with exposures based on smoking patterns of spouses are 1.24 (1.1, 1.4) for females and 1.34 (1.0, 1.8) for males, whereas the RR estimate for occupational ETS exposure and its 95% CI is 1.39 (1.2, 1.7). Using RR estimates for ETS exposure, cigarette equivalents for ETS range from 0.1 to 1.0, based on a range of descriptive and biologically motivated models in active smokers; a cigarette equivalent is 0.2 based on a comparison of log-linear trends in RR with number of cigarettes smoked per day in active smokers and in spouses of nonsmokers. JF - Environmental health perspectives AU - Lubin, J H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-7244, USA. lubinj@exchange.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 879 EP - 883 VL - 107 Suppl 6 SN - 0091-6765, 0091-6765 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - Smoking KW - Epidemiologic Studies KW - Humans KW - Environmental Exposure KW - Research Design KW - Models, Theoretical KW - Lung Neoplasms -- etiology KW - Lung Neoplasms -- epidemiology KW - Tobacco Smoke Pollution -- adverse effects KW - Risk Assessment -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69370783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Estimating+lung+cancer+risk+with+exposure+to+environmental+tobacco+smoke.&rft.au=Lubin%2C+J+H&rft.aulast=Lubin&rft.aufirst=J&rft.date=1999-12-01&rft.volume=107+Suppl+6&rft.issue=&rft.spage=879&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-10 N1 - Date created - 2000-02-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Stat Med. 1995 Mar 15-Apr 15;14(5-7):545-69 [7792447] Int Arch Occup Environ Health. 1994;66(4):269-77 [7843838] Am J Public Health. 1996 May;86(5):748-50 [8629736] BMJ. 1997 Oct 18;315(7114):980-8 [9365295] Am J Public Health. 1998 Jul;88(7):1025-9 [9663148] Br Med J. 1976 Dec 25;2(6051):1525-36 [1009386] J Epidemiol Community Health. 1978 Dec;32(4):303-13 [744822] J Natl Cancer Inst. 1980 Apr;64(4):977-89 [6929006] Prev Med. 1980 Mar;9(2):169-74 [7383981] Public Health Rep. 1980 May-Jun;95(3):213-22 [7384406] J Natl Cancer Inst. 1983 Jun;70(6):1033-9 [6574272] Int J Cancer. 1984 May 15;33(5):569-76 [6724735] J Chronic Dis. 1987;40 Suppl 2:171S-179S [3667864] Stat Med. 1988 Jan-Feb;7(1-2):223-38 [3353605] Stat Med. 1988 Aug;7(8):889-94 [3413368] Risk Anal. 1988 Sep;8(3):383-92 [3201016] Br J Cancer. 1988 Dec;58(6):825-31 [3224084] J Natl Cancer Inst. 1989 Mar 15;81(6):415-20 [2783979] Mutat Res. 1989 Feb;222(2):117-27 [2918871] Epidemiology. 1993 May;4(3):204-17 [8512985] Regul Toxicol Pharmacol. 1994 Jun;19(3):309-16 [8090954] Carcinogenesis. 1995 Jul;16(7):1465-71 [7614679] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MTSEA potentiates 5-HT3 receptors containing the nicotinic alpha4 subunit. AN - 69369113; 10608286 AB - In order to study the subunit composition of 5-HT3 receptors (5-HT3R), we report that (2-aminoethyl)methanethiosulfonate (MTSEA) can enhance the function of both nicotinic ACh receptors (nAChRs) comprised of alpha4/beta2 subunits, and heteromeric channels assembled from serotonin 5-HT3R and alpha4 nAChR subunits. MTSEA has no effect on homomeric 5-HT3 receptor channels. JF - Neuropharmacology AU - Kriegler, S AU - Sudweeks, S AU - Yakel, J L AD - Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C. 27709, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1913 EP - 1915 VL - 38 IS - 12 SN - 0028-3908, 0028-3908 KW - Free Radical Scavengers KW - 0 KW - Indicators and Reagents KW - Receptors, Nicotinic KW - Receptors, Serotonin KW - Receptors, Serotonin, 5-HT3 KW - methanethiosulfonate ethylammonium KW - nicotinic acetylcholine receptor alpha4 subunit KW - Serotonin KW - 333DO1RDJY KW - Ethyl Methanesulfonate KW - 9H154DI0UP KW - Index Medicus KW - Serotonin -- pharmacology KW - Animals KW - Xenopus KW - Free Radical Scavengers -- pharmacology KW - Receptors, Serotonin -- physiology KW - Receptors, Serotonin -- drug effects KW - Ethyl Methanesulfonate -- analogs & derivatives KW - Action Potentials -- physiology KW - Ethyl Methanesulfonate -- pharmacology KW - Indicators and Reagents -- pharmacology KW - Receptors, Nicotinic -- drug effects KW - Action Potentials -- drug effects KW - Receptors, Nicotinic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69369113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuropharmacology&rft.atitle=MTSEA+potentiates+5-HT3+receptors+containing+the+nicotinic+alpha4+subunit.&rft.au=Kriegler%2C+S%3BSudweeks%2C+S%3BYakel%2C+J+L&rft.aulast=Kriegler&rft.aufirst=S&rft.date=1999-12-01&rft.volume=38&rft.issue=12&rft.spage=1913&rft.isbn=&rft.btitle=&rft.title=Neuropharmacology&rft.issn=00283908&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-18 N1 - Date created - 2000-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiformic modulation of endotoxin effects by linomide. AN - 69368407; 10600336 AB - Linomide is a potent immunomodulator that either enhances or suppresses certain immunological processes. Of particular interest is this compound's capacity to inhibit a variety of organ-specific autoimmune diseases. Here, we report on the effects of linomide on several immunological reactions elicited by endotoxin (LPS), both in vivo and in vitro. In rats and mice linomide inhibited the elicitation of endotoxin-induced uveitis (EIU), an acute inflammatory eye disease that develops within 24 h following footpad injection of LPS. Linomide also inhibited the production of TNF-alpha and IL-6 by LPS-stimulated rat and mouse macrophage monolayers. On the other hand, treatment with linomide significantly increased the levels of IL-1beta (mice and less in rats), IL-6 (rats), and TNF-alpha (mice) in serum samples collected 2 h following injection with LPS. The increased production of proinflammatory cytokines in linomide-treated mice was also indicated by the enhanced lethal effect of LPS in these mice. The finding of elevated levels of these cytokines in animals with suppressed EIU is also in line with previous observations of an inverse relationship between EIU severity and levels of TNF-alpha. Data recorded here underscore the unique capacity of linomide to both enhance and suppress the immune system. Copyright 1999 Academic Press. JF - Clinical immunology (Orlando, Fla.) AU - Shalev, M AU - Ko, A AU - Gelderman, M P AU - Fortin, E AU - Reed, G AU - Slavin, S AU - Gery, I AD - The National Eye Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 250 EP - 255 VL - 93 IS - 3 SN - 1521-6616, 1521-6616 KW - Adjuvants, Immunologic KW - 0 KW - Endotoxins KW - Hydroxyquinolines KW - Interleukin-1 KW - Interleukin-6 KW - Lipopolysaccharides KW - Tumor Necrosis Factor-alpha KW - roquinimex KW - 372T2944C0 KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Dose-Response Relationship, Drug KW - Lipopolysaccharides -- pharmacology KW - Interleukin-6 -- metabolism KW - Mice KW - Macrophages -- drug effects KW - Rats KW - Interleukin-1 -- metabolism KW - Cells, Cultured KW - Aqueous Humor -- chemistry KW - Mice, Inbred C3H KW - Tumor Necrosis Factor-alpha -- metabolism KW - Female KW - Macrophages -- metabolism KW - Uveitis -- prevention & control KW - Hydroxyquinolines -- therapeutic use KW - Uveitis -- immunology KW - Uveitis -- chemically induced KW - Adjuvants, Immunologic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69368407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Consumer+Research&rft.atitle=Making+Inferences+About+Missing+Information%3A+The+Effects+of&rft.au=Ross%2C+William+T%2C+Jr%3BCreyer%2C+Elizabeth+H&rft.aulast=Ross&rft.aufirst=William&rft.date=1992-06-01&rft.volume=19&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Journal+of+Consumer+Research&rft.issn=00935301&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. AN - 69368230; 10606239 AB - The mitoxantrone resistance (MXR) gene encodes a recently characterized ATP-binding cassette half-transporter that confers multidrug resistance. We studied resistance to the camptothecins in two sublines expressing high levels of MXR: S1-M1-80 cells derived from parental S1 colon cancer cells and MCF-7 AdVp3,000 isolated from parental MCF-7 breast cancer cells. Both cell lines were 400- to 1,000-fold more resistant to topotecan, 9-amino-20(S)-camptothecin, and the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), than their parental cell lines. The cell lines demonstrated much less resistance to camptothecin and to several camptothecin analogues. Reduced accumulation and energy-dependent efflux of topotecan was demonstrated by confocal microscopy. A significant reduction in cleavable complexes in the resistant cells could be observed after SN-38 treatment but not after camptothecin treatment. In addition to topotecan and SN-38, MXR-overexpressing cells are highly resistant to mitoxantrone and epirubicin. Because these compounds are susceptible to glucuronidation, we examined UDP-glucurono-syltransferase (UGT) activity in parental and resistant cells by TLC. Glucuronides were found at equal levels in both parental and resistant colon cancer cell lines for epirubicin and to a lesser extent for SN-38 and mitoxantrone. Low levels of glucuronidation could also be detected in the resistant breast cancer cells. These results were confirmed by analysis of the UGT1A family mRNAs. We thus conclude that colon and breast cancer cells have a capacity for glucuronidation that could contribute to intrinsic drug resistance in colon cancer cells and may be acquired in breast cancer cells. The lack of selection for higher levels of UGT capacity in the colon cells suggests that high levels of expression of MXR alone are sufficient to confer resistance to the camptothecins. JF - Cancer research AU - Brangi, M AU - Litman, T AU - Ciotti, M AU - Nishiyama, K AU - Kohlhagen, G AU - Takimoto, C AU - Robey, R AU - Pommier, Y AU - Fojo, T AU - Bates, S E AD - Medicine Branch, Division of Cancer Treatment, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 5938 EP - 5946 VL - 59 IS - 23 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Glucuronides KW - irinotecan KW - 0H43101T0J KW - Epirubicin KW - 3Z8479ZZ5X KW - Topotecan KW - 7M7YKX2N15 KW - Mitoxantrone KW - BZ114NVM5P KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Topotecan -- toxicity KW - Microscopy, Confocal KW - Polymerase Chain Reaction KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Breast Neoplasms KW - Epirubicin -- toxicity KW - Female KW - Cell Survival -- drug effects KW - Mitoxantrone -- toxicity KW - ATP-Binding Cassette Transporters -- metabolism KW - Camptothecin -- toxicity KW - Camptothecin -- analogs & derivatives KW - Antineoplastic Agents -- toxicity KW - Glucuronosyltransferase -- metabolism KW - Glucuronides -- metabolism KW - Drug Resistance, Multiple UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69368230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Camptothecin+resistance%3A+role+of+the+ATP-binding+cassette+%28ABC%29%2C+mitoxantrone-resistance+half-transporter+%28MXR%29%2C+and+potential+for+glucuronidation+in+MXR-expressing+cells.&rft.au=Brangi%2C+M%3BLitman%2C+T%3BCiotti%2C+M%3BNishiyama%2C+K%3BKohlhagen%2C+G%3BTakimoto%2C+C%3BRobey%2C+R%3BPommier%2C+Y%3BFojo%2C+T%3BBates%2C+S+E&rft.aulast=Brangi&rft.aufirst=M&rft.date=1999-12-01&rft.volume=59&rft.issue=23&rft.spage=5938&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment with tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor increases epidermal Langerhans' cell numbers in cancer patients. AN - 69364103; 10600331 AB - Dendritic cells (DCs) initiate primary and stimulate secondary T-cell responses. We conducted a phase I trial of tumor necrosis factor (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with cancer to increase DCs in peripheral blood or skin based on in vitro data that showed that CD34(+) hematopoietic precursors require these cytokines to mature into functional antigen-presenting DCs. Eleven patients were treated for 7 days with GM-CSF, 125 microg/m(2) twice daily as subcutaneous injections, and TNF-alpha as a continuous infusion at dose levels of 25, 50, or 100 microg/m(2)/day. The maximum tolerated dose of TNF-alpha was 50 microg/m(2)/day with this dose of GM-CSF; dose-limiting toxicities occurred in both patients treated with 100 microg/m(2)/day. One became thrombocytopenic and the other had transient confusion. Epidermal Langerhans' cells were quantitated by S100 staining of skin biopsies and DC precursors in peripheral blood by colony-forming unit dendritic (CFU-dendritic) assays. S100-positive cells in the epidermis doubled after treatment (2.55 S100(+) cells/high-power field before treatment to 6.05 after treatment, p = 0.029). CFU-dendritic in peripheral blood increased after treatment in 3 colorectal cancer patients but not in 3 patients with melanoma. CD11c(+) or CD123(+), HLA-DR(bright), lineage-negative dendritic cell precursors were not increased in peripheral blood mononuclear cells. This trial demonstrates that treatment with TNF-alpha and GM-CSF can increase the number of DCs in the skin and the number of dendritic cell precursors in the blood of some patients with cancer. This approach may increase the efficacy of vaccination to tumor antigens in cancer patients. JF - Clinical immunology (Orlando, Fla.) AU - Janik, J E AU - Miller, L L AU - Kopp, W C AU - Taub, D D AU - Dawson, H AU - Stevens, D AU - Kostboth, P AU - Curti, B D AU - Conlon, K C AU - Dunn, B K AU - Donegan, S E AU - Ullrich, R AU - Alvord, W G AU - Gause, B L AU - Longo, D L AD - Biological Response Modifiers Program, NCI-FCRDC, 501 W. Seventh Street, Suite 3, Frederick, Maryland 21701-4507, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 209 EP - 221 VL - 93 IS - 3 SN - 1521-6616, 1521-6616 KW - Carcinoembryonic Antigen KW - 0 KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Cell Count KW - Humans KW - Skin -- pathology KW - Biopsy KW - Leukocyte Count KW - Drug Therapy, Combination KW - Leukocytes, Mononuclear -- physiology KW - Adult KW - Thrombocytopenia -- chemically induced KW - Middle Aged KW - Carcinoembryonic Antigen -- blood KW - Flow Cytometry KW - Colony-Forming Units Assay KW - Leukocytes, Mononuclear -- drug effects KW - Colonic Neoplasms -- blood KW - Recombinant Proteins -- therapeutic use KW - Male KW - Female KW - Neoplasms -- drug therapy KW - Langerhans Cells -- drug effects KW - Neoplasms -- pathology KW - Tumor Necrosis Factor-alpha -- therapeutic use KW - Granulocyte-Macrophage Colony-Stimulating Factor -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69364103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+immunology+%28Orlando%2C+Fla.%29&rft.atitle=Treatment+with+tumor+necrosis+factor-alpha+and+granulocyte-macrophage+colony-stimulating+factor+increases+epidermal+Langerhans%27+cell+numbers+in+cancer+patients.&rft.au=Janik%2C+J+E%3BMiller%2C+L+L%3BKopp%2C+W+C%3BTaub%2C+D+D%3BDawson%2C+H%3BStevens%2C+D%3BKostboth%2C+P%3BCurti%2C+B+D%3BConlon%2C+K+C%3BDunn%2C+B+K%3BDonegan%2C+S+E%3BUllrich%2C+R%3BAlvord%2C+W+G%3BGause%2C+B+L%3BLongo%2C+D+L&rft.aulast=Janik&rft.aufirst=J&rft.date=1999-12-01&rft.volume=93&rft.issue=3&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Clinical+immunology+%28Orlando%2C+Fla.%29&rft.issn=15216616&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-resistance enables selective killing of resistant leukemia cells: exploiting of drug resistance instead of reversal. AN - 69362093; 10602425 AB - Drug resistance is a well recognized problem in cancer therapy. Despite the current dogma that drug resistance is always an obstacle for treatment, here I show that it provides opportunities for selective protection of non-resistant cells with killing of drug-resistant cancer cells. According to the proposed 'two-drug' strategy, the first drug should be ineffective against a target drug-resistant cell (ie the drug is a substrate of MRP or Pgp pumps). In addition, it must be cytostatic but not cytotoxic. The second drug, which is applied in sequence, must be a cycle-dependent apoptotic drug to which the target cell is not cross-resistant. Thus, low doses of adriamycin, etoposide and actinomycin D, used as the first drugs, were cytostatic to parental HL60 cells. Therefore, these drugs precluded Bcl-2/Raf-1 phosphorylation, PARP cleavage and cell death which are otherwise induced by paclitaxel, a mitosis-selective apoptotic drug for HL60 cells. In contrast, HL60/ADR cells which express MRP, a transporter which pumps out the first drugs from a cell, were insensitive to the first drugs and therefore readily underwent apoptosis following the second drug. This strategy also allowed a selective killing of HL60/TX cells which express MDR-1, with the only difference being that the second drug, paclitaxel, was substituted for epothilones, non-Pgp substrates. Lack of protection by the first drug, a Pgp substrate, resulted in HL60/TX killing by the second drug, whereas parental HL-60 cells were fully protected. Therefore, drug resistant cells can be selectively killed by a combination of drugs not killing sensitive cells. Lack of toxicity against normal cells will be clinically translated in reduction of adverse side-effects of chemotherapy against drug-resistant malignancies. JF - Leukemia AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, Building 10, R 12N226, NIH, Bethesda, MD 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 2031 EP - 2035 VL - 13 IS - 12 SN - 0887-6924, 0887-6924 KW - Doxorubicin KW - 80168379AG KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Doxorubicin -- pharmacology KW - Cell Survival -- drug effects KW - HL-60 Cells KW - Humans KW - Apoptosis -- drug effects KW - Paclitaxel -- pharmacology KW - Leukemia -- pathology KW - Leukemia -- drug therapy KW - Drug Resistance, Neoplasm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69362093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Drug-resistance+enables+selective+killing+of+resistant+leukemia+cells%3A+exploiting+of+drug+resistance+instead+of+reversal.&rft.au=Blagosklonny%2C+M+V&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1999-12-01&rft.volume=13&rft.issue=12&rft.spage=2031&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells. AN - 69358384; 10598578 AB - Caveolae may function as microdomains for signaling that help to determine specific biological actions mediated by the insulin receptor (IR). Caveolin-1, a major component of caveolae, contains a scaffolding domain (SD) that binds to a caveolin-1 binding motif in the kinase domain of the IR in vitro. To investigate the potential role of caveolin-1 in insulin signaling we overexpressed wild-type (Cav-WT) or mutant (Cav-Mut; F92A/V94A in SD) caveolin-1 in either Cos-7 cells cotransfected with IR or rat adipose cells (low and high levels of endogenous caveolin-1, respectively). Cav-WT coimmunoprecipitated with the IR to a much greater extent than Cav-Mut, suggesting that the SD is important for interactions between caveolin-1 and the IR in intact cells. We also constructed several IR mutants with a disrupted caveolin-1 binding motif and found that these mutants were poorly expressed and did not undergo autophosphorylation. Interestingly, overexpression of Cav-WT in Cos-7 cells significantly enhanced insulin-stimulated phosphorylation of Elk-1 (a mitogen-activated protein kinase-dependent pathway) while overexpression of Cav-Mut was without effect. In contrast, in adipose cells, overexpression of either Cav-WT or Cav-Mut did not affect insulin-stimulated phosphorylation of a cotransfected ERK2 (but did significantly inhibit basal phosphorylation of ERK2). Furthermore, we also observed a small inhibition of insulin-stimulated translocation of GLUT4 when either Cav-WT or Cav-Mut was overexpressed in adipose cells. Thus, interaction of caveolin-1 with IRs may differentially modulate insulin signaling to enhance insulin action in Cos-7 cells but inhibit insulin's effects in adipose cells. JF - Molecular endocrinology (Baltimore, Md.) AU - Nystrom, F H AU - Chen, H AU - Cong, L N AU - Li, Y AU - Quon, M J AD - Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 2013 EP - 2024 VL - 13 IS - 12 SN - 0888-8809, 0888-8809 KW - Cav1 protein, rat KW - 0 KW - Caveolin 1 KW - Caveolins KW - Glucose Transporter Type 4 KW - Insulin KW - Membrane Proteins KW - Monosaccharide Transport Proteins KW - Muscle Proteins KW - Recombinant Proteins KW - Slc2a4 protein, rat KW - Receptor, Insulin KW - EC 2.7.10.1 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Monosaccharide Transport Proteins -- metabolism KW - Phosphorylation KW - Transfection KW - Gene Expression KW - Immunosorbent Techniques KW - Male KW - Receptor, Insulin -- genetics KW - COS Cells -- metabolism KW - Insulin -- metabolism KW - Insulin -- pharmacology KW - Adipocytes -- metabolism KW - Membrane Proteins -- genetics KW - Receptor, Insulin -- physiology KW - Signal Transduction KW - Membrane Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69358384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Caveolin-1+interacts+with+the+insulin+receptor+and+can+differentially+modulate+insulin+signaling+in+transfected+Cos-7+cells+and+rat+adipose+cells.&rft.au=Nystrom%2C+F+H%3BChen%2C+H%3BCong%2C+L+N%3BLi%2C+Y%3BQuon%2C+M+J&rft.aulast=Nystrom&rft.aufirst=F&rft.date=1999-12-01&rft.volume=13&rft.issue=12&rft.spage=2013&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-10 N1 - Date created - 2000-01-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rapid evolution of the ribonuclease A superfamily: adaptive expansion of independent gene clusters in rats and mice. AN - 69355665; 10594173 AB - The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have occurred at these loci recently, sometime after the divergence of these two rodent species ( approximately 10-15 million years ago). Nonsynonymous substitutions per site (d(N)) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated rates, and comparisons of nonsynonymous to synonymous substitution (d(N) / d(S)) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain, our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense. JF - Journal of molecular evolution AU - Singhania, N A AU - Dyer, K D AU - Zhang, J AU - Deming, M S AU - Bonville, C A AU - Domachowske, J B AU - Rosenberg, H F AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10 Bethesda, MD 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 721 EP - 728 VL - 49 IS - 6 SN - 0022-2844, 0022-2844 KW - RNA, Messenger KW - 0 KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Index Medicus KW - Phylogeny KW - Animals KW - Humans KW - RNA, Messenger -- analysis KW - Amino Acid Sequence KW - Mice KW - RNA, Messenger -- genetics KW - Selection, Genetic KW - Rats KW - Conserved Sequence -- genetics KW - Sequence Alignment KW - Amino Acid Motifs KW - Genes, Duplicate -- genetics KW - Molecular Sequence Data KW - Time Factors KW - Amino Acid Substitution KW - Multigene Family -- genetics KW - Ribonuclease, Pancreatic -- metabolism KW - Ribonuclease, Pancreatic -- chemistry KW - Evolution, Molecular KW - Ribonuclease, Pancreatic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69355665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Process+Biochemistry&rft.atitle=The+effect+of+soy+protein+hydrolyzates+on+fermentation+by+Lactobacillus+amylovorus&rft.au=Hsieh%2C+C+M%3BYang%2C+Fan-Chiang%3BIannotti%2C+EL&rft.aulast=Hsieh&rft.aufirst=C&rft.date=1999-02-01&rft.volume=34&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Process+Biochemistry&rft.issn=00329592&rft_id=info:doi/10.1016%2FS0032-9592%2898%2900081-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys. AN - 69352332; 10594668 AB - All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibres of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala with those induced by fibre-sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of defence, aggression, submission and approach responses. In unoperated controls, defence and approach behaviours were elicited by all four stimuli, 'social' and inanimate alike, whereas aggression and submission responses occurred only in the presence of the two 'social' stimuli. Furthermore, all defence reactions were reduced with an attractive inanimate item, while freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioural changes as those with aspiration lesions, i.e. reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two-thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, because some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fibre damage. JF - The European journal of neuroscience AU - Meunier, M AU - Bachevalier, J AU - Murray, E A AU - Málková, L AU - Mishkin, M AD - Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD, USA. Meunier@Isc.Cnrs.Fr Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 4403 EP - 4418 VL - 11 IS - 12 SN - 0953-816X, 0953-816X KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Magnetic Resonance Imaging KW - Animals KW - Photic Stimulation KW - Dominance-Subordination KW - Behavior, Animal -- physiology KW - Macaca mulatta KW - Physical Stimulation KW - Fear -- physiology KW - Male KW - Aggression -- physiology KW - Affective Symptoms -- physiopathology KW - Amygdala -- physiopathology KW - Affective Symptoms -- chemically induced KW - Amygdala -- injuries KW - Amygdala -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69352332?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+European+journal+of+neuroscience&rft.atitle=Effects+of+aspiration+versus+neurotoxic+lesions+of+the+amygdala+on+emotional+responses+in+monkeys.&rft.au=Meunier%2C+M%3BBachevalier%2C+J%3BMurray%2C+E+A%3BM%C3%A1lkov%C3%A1%2C+L%3BMishkin%2C+M&rft.aulast=Meunier&rft.aufirst=M&rft.date=1999-12-01&rft.volume=11&rft.issue=12&rft.spage=4403&rft.isbn=&rft.btitle=&rft.title=The+European+journal+of+neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-10 N1 - Date created - 2000-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N-nitrosoethylurea. AN - 69345592; 10592097 AB - Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat. Pregnant C3H/HeNCr mice received 0.4 micromol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in 11 of the 201 offspring. Missense T --> A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was predominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios. JF - Journal of cancer research and clinical oncology AU - Buzard, G S AU - Enomoto, T AU - Anderson, L M AU - Perantoni, A O AU - Devor, D E AU - Rice, J M AD - Intramural Research Support Program, SAIC Frederick, Bldg. 538, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. buzardg@mail.ncifcrf.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 653 EP - 659 VL - 125 IS - 12 SN - 0171-5216, 0171-5216 KW - DNA, Neoplasm KW - 0 KW - Membrane Proteins KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Animals KW - Sequence Homology, Nucleic Acid KW - DNA, Neoplasm -- chemistry KW - Maternal-Fetal Exchange KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Mice, Inbred C3H KW - Molecular Sequence Data KW - Point Mutation KW - CHO Cells KW - Gene Expression Regulation KW - Sequence Homology, Amino Acid KW - Cell Transformation, Neoplastic -- genetics KW - 3T3 Cells KW - DNA Mutational Analysis KW - Amino Acid Sequence KW - Mice KW - Sequence Analysis, DNA KW - Binding Sites KW - Pregnancy KW - Base Sequence KW - Transfection KW - Polymorphism, Restriction Fragment Length KW - DNA, Neoplasm -- genetics KW - Protein Structure, Tertiary KW - Female KW - Cricetinae KW - Receptor, ErbB-2 -- genetics KW - Neurilemmoma -- chemically induced KW - Ethylnitrosourea -- toxicity KW - Membrane Proteins -- chemistry KW - Neurilemmoma -- pathology KW - Receptor, ErbB-2 -- chemistry KW - Placenta -- drug effects KW - Neurilemmoma -- genetics KW - Membrane Proteins -- genetics KW - Placenta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69345592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cancer+research+and+clinical+oncology&rft.atitle=Activation+of+neu+by+missense+point+mutation+in+the+transmembrane+domain+in+schwannomas+induced+in+C3H%2FHeNCr+mice+by+transplacental+exposure+to+N-nitrosoethylurea.&rft.au=Buzard%2C+G+S%3BEnomoto%2C+T%3BAnderson%2C+L+M%3BPerantoni%2C+A+O%3BDevor%2C+D+E%3BRice%2C+J+M&rft.aulast=Buzard&rft.aufirst=G&rft.date=1999-12-01&rft.volume=125&rft.issue=12&rft.spage=653&rft.isbn=&rft.btitle=&rft.title=Journal+of+cancer+research+and+clinical+oncology&rft.issn=01715216&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-28 N1 - Date created - 1999-12-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - T cell receptor-induced activation and apoptosis in cycling human T cells occur throughout the cell cycle. AN - 69342378; 10588669 AB - Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0-G1, S, and G2-M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca(2+) flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle. JF - Molecular biology of the cell AU - Karas, M AU - Zaks, T Z AU - Liu, J L AU - LeRoith, D AD - Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-1770, USA. karas@box-k.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 4441 EP - 4450 VL - 10 IS - 12 SN - 1059-1524, 1059-1524 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD3 KW - Antigens, Surface KW - FASLG protein, human KW - Fas Ligand Protein KW - Membrane Glycoproteins KW - Receptors, Antigen, T-Cell KW - Recombinant Proteins KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Antigens, CD3 -- metabolism KW - Cell Cycle -- physiology KW - Humans KW - Antigens, Surface -- immunology KW - Antigens, CD3 -- immunology KW - Calcium -- metabolism KW - Tumor Cells, Cultured KW - Recombinant Proteins -- metabolism KW - Antigens, Surface -- metabolism KW - Membrane Glycoproteins -- immunology KW - Membrane Glycoproteins -- metabolism KW - T-Lymphocytes -- metabolism KW - Apoptosis -- physiology KW - Receptors, Antigen, T-Cell -- metabolism KW - Lymphocyte Activation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69342378?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=T+cell+receptor-induced+activation+and+apoptosis+in+cycling+human+T+cells+occur+throughout+the+cell+cycle.&rft.au=Karas%2C+M%3BZaks%2C+T+Z%3BLiu%2C+J+L%3BLeRoith%2C+D&rft.aulast=Karas&rft.aufirst=M&rft.date=1999-12-01&rft.volume=10&rft.issue=12&rft.spage=4441&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-14 N1 - Date created - 2000-02-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunity. 1997 Feb;6(2):209-15 [9047242] N Engl J Med. 1996 Nov 28;335(22):1643-9 [8929361] J Immunol Methods. 1997 Apr 11;203(1):25-33 [9134027] J Exp Med. 1997 May 5;185(9):1549-56 [9151892] J Immunol. 1997 Jun 15;158(12):5612-8 [9190908] FEBS Lett. 1997 Jul 21;412(1):91-3 [9257696] J Immunol. 1997 Nov 1;159(9):4261-7 [9379021] Oncogene. 1997 Nov 27;15(22):2749-53 [9401002] Cytometry. 1998 Jan 1;31(1):1-9 [9450519] Immunity. 1998 Jan;8(1):57-65 [9462511] J Exp Med. 1998 Apr 6;187(7):1057-67 [9529322] J Immunol. 1998 Jul 1;161(1):168-74 [9647221] Methods Cell Biol. 1998;57:229-49 [9648108] Cell Immunol. 1978 Feb;35(2):414-26 [145901] J Exp Med. 1981 Aug 1;154(2):575-80 [6973610] J Biol Chem. 1985 Mar 25;260(6):3440-50 [3838314] J Exp Med. 1987 Jan 1;165(1):173-94 [3491868] J Immunol Methods. 1987 Aug 24;102(1):127-41 [3305708] N Engl J Med. 1988 Dec 22;319(25):1676-80 [3264384] J Immunol Methods. 1990 Apr 17;128(2):189-201 [1691237] Science. 1990 Dec 21;250(4988):1726-9 [2125368] Science. 1991 Mar 8;251(4998):1225-8 [1900951] Annu Rev Immunol. 1991;9:243-69 [1910678] Nature. 1991 Oct 31;353(6347):858-61 [1944559] Anticancer Res. 1992 May-Jun;12(3):773-9 [1622137] J Exp Med. 1993 Jan 1;177(1):195-200 [7678113] Am J Physiol. 1992 Dec;263(6 Pt 1):C1119-40 [1282295] Eur J Immunol. 1993 Jul;23(7):1552-60 [8325332] Int Immunol. 1993 Jun;5(6):625-30 [7688561] Immunol Today. 1993 Jul;14(7):338-9 [8363721] Biochem Pharmacol. 1993 Dec 3;46(11):1909-16 [8267640] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9488-93 [9689107] Cancer Res. 1998 Nov 1;58(21):4902-8 [9809997] J Immunol. 1999 Mar 15;162(6):3273-9 [10092779] J Immunol. 1999 May 1;162(9):5205-11 [10227994] Nature. 1995 Feb 2;373(6513):444-8 [7530337] J Immunol. 1995 Jan 1;154(1):192-200 [7995939] Mol Cell Biol. 1995 Feb;15(2):932-42 [7823958] Nature. 1995 Feb 2;373(6513):438-41 [7530335] Nature. 1995 Feb 2;373(6513):441-4 [7530336] EMBO J. 1995 Mar 15;14(6):1129-35 [7536672] Exp Cell Res. 1995 Aug;219(2):699-708 [7543858] Eur J Immunol. 1995 Aug;25(8):2253-8 [7545115] N Engl J Med. 1995 Oct 19;333(16):1038-44 [7675046] Nature. 1995 Sep 28;377(6547):348-51 [7566090] Blood. 1995 Nov 15;86(10):3848-60 [7579353] Mutagenesis. 1995 Sep;10(5):385-91 [8544750] Immunity. 1996 Mar;4(3):321-8 [8624822] J Biol Chem. 1996 May 10;271(19):11148-55 [8626660] J Immunol. 1996 Jun 1;156(11):4075-8 [8666771] Cell Immunol. 1996 Jun 15;170(2):260-73 [8660826] J Exp Med. 1996 Jul 1;184(1):277-81 [8691143] Scanning Microsc. 1995 Jun;9(2):509-16; discussion 516-8 [8714746] Lancet. 1996 Sep 14;348(9029):719-23 [8806292] Science. 1996 Oct 4;274(5284):94-6 [8810254] Curr Opin Genet Dev. 1996 Feb;6(1):12-8 [8791489] Science. 1996 Oct 4;274(5284):67-8 [8848725] J Immunol. 1996 Nov 15;157(10):4309-15 [8906804] Leuk Lymphoma. 1997 Mar;25(1-2):9-21 [9130610] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A discrete stage of baculovirus GP64-mediated membrane fusion. AN - 69337150; 10588652 AB - Viral fusion protein trimers can play a critical role in limiting lipids in membrane fusion. Because the trimeric oligomer of many viral fusion proteins is often stabilized by hydrophobic 4-3 heptad repeats, higher-order oligomers might be stabilized by similar sequences. There is a hydrophobic 4-3 heptad repeat contiguous to a putative oligomerization domain of Autographa californica multicapsid nucleopolyhedrovirus envelope glycoprotein GP64. We performed mutagenesis and peptide inhibition studies to determine if this sequence might play a role in catalysis of membrane fusion. First, leucine-to-alanine mutants within and flanking the amino terminus of the hydrophobic 4-3 heptad repeat motif that oligomerize into trimers and traffic to insect Sf9 cell surfaces were identified. These mutants retained their wild-type conformation at neutral pH and changed conformation in acidic conditions, as judged by the reactivity of a conformationally sensitive mAb. These mutants, however, were defective for membrane fusion. Second, a peptide encoding the portion flanking the GP64 hydrophobic 4-3 heptad repeat was synthesized. Adding peptide led to inhibition of membrane fusion, which occurred only when the peptide was present during low pH application. The presence of peptide during low pH application did not prevent low pH-induced conformational changes, as determined by the loss of a conformationally sensitive epitope. In control experiments, a peptide of identical composition but different sequence, or a peptide encoding a portion of the Ebola GP heptad motif, had no effect on GP64-mediated fusion. Furthermore, when the hemagglutinin (X31 strain) fusion protein of influenza was functionally expressed in Sf9 cells, no effect on hemagglutinin-mediated fusion was observed, suggesting that the peptide does not exert nonspecific effects on other fusion proteins or cell membranes. Collectively, these studies suggest that the specific peptide sequences of GP64 that are adjacent to and include portions of the hydrophobic 4-3 heptad repeat play a dynamic role in membrane fusion at a stage that is downstream of the initiation of protein conformational changes but upstream of lipid mixing. JF - Molecular biology of the cell AU - Kingsley, D H AU - Behbahani, A AU - Rashtian, A AU - Blissard, G W AU - Zimmerberg, J AD - Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1855, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 4191 EP - 4200 VL - 10 IS - 12 SN - 1059-1524, 1059-1524 KW - Cell Adhesion Molecules KW - 0 KW - Membrane Glycoproteins KW - Viral Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Molecular Sequence Data KW - Enzyme-Linked Immunosorbent Assay KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Mutation KW - Leucine Zippers KW - Cell Line KW - Membrane Glycoproteins -- chemistry KW - Cell Adhesion Molecules -- genetics KW - Membrane Fusion -- physiology KW - Insects -- virology KW - Cell Adhesion Molecules -- metabolism KW - Nucleopolyhedrovirus -- metabolism KW - Cell Adhesion Molecules -- chemistry KW - Membrane Glycoproteins -- metabolism KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69337150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Neutralizing+antibody+directed+against+the+HIV-1+envelope+glycoprotein+can+completely+block+HIV-1%2FSIV+chimeric+virus+infections+of+macaque+monkeys&rft.au=Shibata%2C+R%3BIgarashi%2C+T%3BHaigwood%2C+N%3BBuckler-White%2C+A%3BOgert%2C+R%3BRoss%2C+W%3BWilley%2C+R%3BCho%2C+M+W%3BMartin%2C+MA&rft.aulast=Shibata&rft.aufirst=R&rft.date=1999-02-01&rft.volume=5&rft.issue=2&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-14 N1 - Date created - 2000-02-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9134-9 [9689046] Virology. 1998 Aug 15;248(1):20-34 [9705252] Nature. 1998 Sep 24;395(6700):347-53 [9759724] J Cell Biol. 1998 Nov 30;143(5):1155-66 [9832546] J Mol Biol. 1999 Jan 15;285(2):609-25 [9878433] Virology. 1999 Jan 5;253(1):65-76 [9887319] Virology. 1999 Feb 1;254(1):147-59 [9927582] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2662-7 [10077567] Mol Cell. 1999 Mar;3(3):309-19 [10198633] Mol Membr Biol. 1999 Jan-Mar;16(1):3-9 [10332732] J Virol. 1999 Jul;73(7):5945-56 [10364347] Virology. 1999 Jun 5;258(2):455-68 [10366584] J Virol. 1989 Mar;63(3):1393-9 [2644449] Nature. 1989 Apr 13;338(6216):547 [2927513] Virology. 1989 Jun;170(2):537-55 [2658304] Biochemistry. 1990 Oct 16;29(41):9697-707 [2271610] J Gen Virol. 1990 Dec;71 ( Pt 12):3075-80 [2177097] J Virol. 1991 May;65(5):2402-7 [1850019] Science. 1991 May 24;252(5009):1162-4 [2031185] J Virol. 1991 Nov;65(11):5820-7 [1920618] J Gen Virol. 1992 Jul;73 ( Pt 7):1703-7 [1629696] J Virol. 1992 Aug;66(8):4748-56 [1629954] J Virol. 1992 Nov;66(11):6829-35 [1404622] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10537-41 [1438243] J Cell Biol. 1993 May;121(3):543-52 [8486735] Cell. 1993 May 21;73(4):823-32 [8500173] Nature. 1993 Sep 9;365(6442):113 [8371754] Biochem Biophys Res Commun. 1993 Sep 15;195(2):533-8 [8373393] J Virol. 1994 Feb;68(2):813-22 [8289385] Nature. 1994 Sep 1;371(6492):37-43 [8072525] J Virol. 1994 Nov;68(11):7654-8 [7933158] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9770-4 [7937889] Virology. 1994 Nov 15;205(1):300-13 [7975226] J Cell Biol. 1994 Dec;127(6 Pt 2):1885-94 [7806567] Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12676-80 [7809100] J Virol. 1995 Apr;69(4):2583-95 [7533858] J Virol. 1995 Jun;69(6):3771-7 [7538176] Virology. 1995 Jun 1;209(2):592-603 [7778291] AIDS Res Hum Retroviruses. 1995 Mar;11(3):323-5 [7786578] Biochemistry. 1995 Jul 11;34(27):8642-8 [7612604] J Virol. 1995 Oct;69(10):5995-6004 [7666504] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8259-63 [7667278] Biochemistry. 1995 Oct 17;34(41):13390-7 [7577925] Protein Sci. 1995 Aug;4(8):1596-607 [8520486] Biochemistry. 1995 Nov 21;34(46):14955-62 [7578108] EMBO J. 1995 Nov 15;14(22):5524-31 [8521809] Nat Struct Biol. 1995 Dec;2(12):1075-82 [8846219] Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3602-7 [8622982] Nat Struct Biol. 1996 May;3(5):465-9 [8612078] EMBO J. 1996 Apr 1;15(7):1507-14 [8612573] J Cell Biol. 1996 May;133(3):559-69 [8636231] J Virol. 1996 Jul;70(7):4607-16 [8676487] Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2186-91 [8700906] Curr Biol. 1995 Dec 1;5(12):1377-83 [8749390] Virology. 1996 Sep 1;223(1):103-12 [8806544] J Cell Biol. 1996 Oct;135(1):63-71 [8858163] Proteins. 1996 Oct;26(2):134-45 [8916221] J Cell Biol. 1996 Dec;135(6 Pt 2):1831-9 [8991094] J Gen Virol. 1997 Jan;78 ( Pt 1):107-11 [9010292] Cell. 1997 Apr 18;89(2):263-73 [9108481] Nature. 1997 May 22;387(6631):426-30 [9163431] Virology. 1997 May 12;231(2):167-81 [9168879] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13426-30 [9391041] Biochemistry. 1997 Dec 9;36(49):15451-62 [9398274] Virology. 1997 Nov 24;238(2):291-304 [9400602] J Virol. 1998 Feb;72(2):986-93 [9444991] J Cell Biol. 1998 Jan 26;140(2):315-23 [9442107] J Cell Biol. 1998 Mar 23;140(6):1369-82 [9508770] Nat Struct Biol. 1998 Apr;5(4):276-9 [9546217] Proc Natl Acad Sci U S A. 1998 May 26;95(11):6032-6 [9600912] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association between lower serum free T4 and greater mood instability and depression in lithium-maintained bipolar patients. AN - 69334621; 10588404 AB - This investigation evaluated the relationship between changes in thyroid indices and mood stability during lithium and carbamazepine prophylaxis for bipolar disorder. In the first 2 years, 30 patients with bipolar mood disorder were randomly assigned to 1 year of lithium and then 1 year of carbamazepine, or vice versa; in the third year, they received lithium plus carbamazepine. By stepwise regression analysis, the degree and timing of lithium- and carbamazepine-induced thyroid changes and their subsequent relationship to long-term mood stability were evaluated. During the lithium phase, there was a significant inverse relationship between morbidity and mean serum level of free T4, i.e., a lower mean serum level of free T4 was associated with more affective episodes and greater severity of depression as shown by the Beck Depression Inventory. During the carbamazepine phase, there was an inverse relationship between mean level of total T4 and global severity rating. During the combination phase, no relationships between thyroid indices and clinical outcome were significant. In the lithium phase, a low level of free T4 was associated with more affective episodes and greater severity of depression. Whether this mood instability is causally related to low free T4 levels and whether it can be attenuated with T4 replacement remain to be studied in a controlled setting. JF - The American journal of psychiatry AU - Frye, M A AU - Denicoff, K D AU - Bryan, A L AU - Smith-Jackson, E E AU - Ali, S O AU - Luckenbaugh, D AU - Leverich, G S AU - Post, R M AD - Biological Psychiatry Branch, NIMH, NIH, Bethesda, MD 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 1909 EP - 1914 VL - 156 IS - 12 SN - 0002-953X, 0002-953X KW - Carbamazepine KW - 33CM23913M KW - Lithium KW - 9FN79X2M3F KW - Thyroxine KW - Q51BO43MG4 KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Affect -- drug effects KW - Double-Blind Method KW - Humans KW - Hypothyroidism -- epidemiology KW - Carbamazepine -- therapeutic use KW - Hypothyroidism -- chemically induced KW - Comorbidity KW - Drug Therapy, Combination KW - Treatment Outcome KW - Carbamazepine -- pharmacology KW - Incidence KW - Female KW - Male KW - Bipolar Disorder -- blood KW - Lithium -- therapeutic use KW - Bipolar Disorder -- psychology KW - Thyroxine -- blood KW - Bipolar Disorder -- prevention & control KW - Lithium -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69334621?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Association+between+lower+serum+free+T4+and+greater+mood+instability+and+depression+in+lithium-maintained+bipolar+patients.&rft.au=Frye%2C+M+A%3BDenicoff%2C+K+D%3BBryan%2C+A+L%3BSmith-Jackson%2C+E+E%3BAli%2C+S+O%3BLuckenbaugh%2C+D%3BLeverich%2C+G+S%3BPost%2C+R+M&rft.aulast=Frye&rft.aufirst=M&rft.date=1999-12-01&rft.volume=156&rft.issue=12&rft.spage=1909&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. AN - 69334164; 10581258 AB - Components of the ras signaling pathway contribute to activation of cellular p53. In MCF-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at Ser33 and Ser46, a newly identified site. Mutation of these sites decreased p53-mediated and UV-induced apoptosis, and the reduction correlated with total abrogation of UV-induced phosphorylation on Ser37 and a significant decrease in Ser15 phosphorylation in mutant p53 containing alanine at Ser33 and Ser46. Inhibition of p38 activation after UV irradiation decreased phosphorylation of Ser33, Ser37 and Ser15, and also markedly reduced UV-induced apoptosis in a p53-dependent manner. These results suggest that p38 kinase plays a prominent role in an integrated regulation of N-terminal phosphorylation that regulates p53-mediated apoptosis after UV radiation. JF - The EMBO journal AU - Bulavin, D V AU - Saito, S AU - Hollander, M C AU - Sakaguchi, K AU - Anderson, C W AU - Appella, E AU - Fornace, A J AD - Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 6845 EP - 6854 VL - 18 IS - 23 SN - 0261-4189, 0261-4189 KW - Tumor Suppressor Protein p53 KW - 0 KW - Serine KW - 452VLY9402 KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - p38 Mitogen-Activated Protein Kinases KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Plasmids -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation -- radiation effects KW - DNA Damage KW - Alanine -- metabolism KW - Humans KW - Transcription, Genetic KW - Flow Cytometry KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - Time Factors KW - Serine -- metabolism KW - Ultraviolet Rays KW - Mitogen-Activated Protein Kinases -- metabolism KW - Apoptosis -- radiation effects KW - Tumor Suppressor Protein p53 -- genetics KW - Mitogen-Activated Protein Kinases -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69334164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Phosphorylation+of+human+p53+by+p38+kinase+coordinates+N-terminal+phosphorylation+and+apoptosis+in+response+to+UV+radiation.&rft.au=Bulavin%2C+D+V%3BSaito%2C+S%3BHollander%2C+M+C%3BSakaguchi%2C+K%3BAnderson%2C+C+W%3BAppella%2C+E%3BFornace%2C+A+J&rft.aulast=Bulavin&rft.aufirst=D&rft.date=1999-12-01&rft.volume=18&rft.issue=23&rft.spage=6845&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-31 N1 - Date created - 2000-01-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic expression of green fluorescent protein in mouse oxytocin neurones. AN - 69332323; 10583728 AB - Routine targeting of neurones for expression of exogenous genes would facilitate our ability to manipulate their internal milieu or functions, providing insight into physiology of neurones. The magnocellular neurones of the paraventricular and supraoptic nuclei of the hypothalamus have been the objects of limited success by this approach. Here we report on the placement of the enhanced green fluorescent protein (eGFP) coding sequence at various locations within an oxytocin transgene. Placement within the first exon yielded little to no expression, whereas placement in the third exon (as an in-frame fusion with the carboxyl terminus of the oxytocin preprohormone) resulted in cell-specific expression of eGFP in oxytocin neurones. Furthermore, placement of the eGFP sequence downstream of a picornavirus internal ribosomal entry site (IRES), also in the third exon, allowed expression of the eGFP as a separate protein. Other coding sequences should now be amenable to expression within oxytocin neurones to study their physiology. JF - Journal of neuroendocrinology AU - Young, W S AU - Iacangelo, A AU - Luo, X Z AU - King, C AU - Duncan, K AU - Ginns, E I AD - Section on Neural Gene Expression, National Institute of Mental Health, Bethesda, MD 20892-4068, USA. scott@codon.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 935 EP - 939 VL - 11 IS - 12 SN - 0953-8194, 0953-8194 KW - Antibodies KW - 0 KW - Indicators and Reagents KW - Luminescent Proteins KW - Vasopressins KW - 11000-17-2 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Oxytocin KW - 50-56-6 KW - Index Medicus KW - Animals KW - Indicators and Reagents -- metabolism KW - Supraoptic Nucleus -- cytology KW - Vasopressins -- analysis KW - Vasopressins -- physiology KW - Mutagenesis -- physiology KW - Mice KW - Ribosomes -- physiology KW - Mice, Transgenic KW - Paraventricular Hypothalamic Nucleus -- cytology KW - Oxytocin -- physiology KW - Neurons -- chemistry KW - Luminescent Proteins -- analysis KW - Oxytocin -- analysis KW - Neurons -- physiology KW - Genes, Reporter KW - Luminescent Proteins -- immunology KW - Luminescent Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69332323?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroendocrinology&rft.atitle=Transgenic+expression+of+green+fluorescent+protein+in+mouse+oxytocin+neurones.&rft.au=Young%2C+W+S%3BIacangelo%2C+A%3BLuo%2C+X+Z%3BKing%2C+C%3BDuncan%2C+K%3BGinns%2C+E+I&rft.aulast=Young&rft.aufirst=W&rft.date=1999-12-01&rft.volume=11&rft.issue=12&rft.spage=935&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroendocrinology&rft.issn=09538194&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-18 N1 - Date created - 2000-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. AN - 69321300; 10580025 AB - Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population. Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke. When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure. A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele). JF - Journal of the National Cancer Institute AU - Bennett, W P AU - Alavanja, M C AU - Blomeke, B AU - Vähäkangas, K H AU - Castrén, K AU - Welsh, J A AU - Bowman, E D AU - Khan, M A AU - Flieder, D B AU - Harris, C C AD - (Laboratory of Human Carcinogenesis, Division of Basic Sciences), National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 2009 EP - 2014 VL - 91 IS - 23 SN - 0027-8874, 0027-8874 KW - Tobacco Smoke Pollution KW - 0 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - glutathione S-transferase T1 KW - EC 2.5.1.- KW - Glutathione Transferase KW - EC 2.5.1.18 KW - glutathione S-transferase M1 KW - Index Medicus KW - Genotype KW - Polymorphism, Genetic KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Aged KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Lung Neoplasms -- epidemiology KW - Glutathione Transferase -- metabolism KW - Tobacco Smoke Pollution -- adverse effects KW - Lung Neoplasms -- genetics KW - Glutathione Transferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69321300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Environmental+tobacco+smoke%2C+genetic+susceptibility%2C+and+risk+of+lung+cancer+in+never-smoking+women.&rft.au=Bennett%2C+W+P%3BAlavanja%2C+M+C%3BBlomeke%2C+B%3BV%C3%A4h%C3%A4kangas%2C+K+H%3BCastr%C3%A9n%2C+K%3BWelsh%2C+J+A%3BBowman%2C+E+D%3BKhan%2C+M+A%3BFlieder%2C+D+B%3BHarris%2C+C+C&rft.aulast=Bennett&rft.aufirst=W&rft.date=1999-12-01&rft.volume=91&rft.issue=23&rft.spage=2009&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-21 N1 - Date created - 1999-12-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 1999 Dec 1;91(23):1985-6 [10580013] J Natl Cancer Inst. 2000 May 3;92(9):760-1 [10793123] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells. AN - 69311921; 10580424 AB - In this article, we show that glucagon-like peptide 1 (GLP-1) can induce AR42J cells to differentiate into insulin, pancreatic polypeptide, and glucagon-positive cells. In their natural state, these cells, which are derived from a chemically induced pancreatic tumor, possess exocrine and neuroendocrine properties but are negative for islet hormones and their mRNAs. We found that when these cells were exposed to GLP-1 (1 or 10 nmol), a peptide normally released from the gut in response to food and a modulator of insulin release, intracellular cAMP levels were increased, and proliferation of cells was increased for the first 24 h, followed by inhibition. Up to 50% of the cells became positive for islet hormones. The mRNAs for glucose transporter 2 and glucokinase were detected in the GLP-1-treated cells. Insulin was detected by radioimmunoassay (RIA) in the medium of GLP-1-treated cells, and the cells were capable of releasing insulin in a glucose-mediated fashion. Exendin-4, an analog of GLP-1, in some critical experiments performed in a similar manner to GLP-1, with the exception of it being 10-fold more potent. We therefore propose that GLP-1 and exendin-4 are capable of causing pancreatic precursor cells to differentiate into islet cells. JF - Diabetes AU - Zhou, J AU - Wang, X AU - Pineyro, M A AU - Egan, J M AD - Diabetes Section, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 2358 EP - 2366 VL - 48 IS - 12 SN - 0012-1797, 0012-1797 KW - Insulin KW - 0 KW - Peptide Fragments KW - Peptides KW - Protein Precursors KW - Venoms KW - Dexamethasone KW - 7S5I7G3JQL KW - Glucagon-Like Peptide 1 KW - 89750-14-1 KW - Glucagon KW - 9007-92-5 KW - Cholecystokinin KW - 9011-97-6 KW - exenatide KW - 9P1872D4OL KW - Amylases KW - EC 3.2.1.- KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dexamethasone -- pharmacology KW - Pancreatic Neoplasms KW - Adenylyl Cyclases -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rats KW - Tumor Cells, Cultured KW - Kinetics KW - Gene Expression Regulation KW - Amylases -- secretion KW - Cholecystokinin -- pharmacology KW - Cell Cycle KW - Venoms -- pharmacology KW - Protein Precursors -- pharmacology KW - Glucagon -- genetics KW - Insulin -- biosynthesis KW - Cell Differentiation -- physiology KW - Glucagon -- biosynthesis KW - Peptide Fragments -- pharmacology KW - Glucagon -- pharmacology KW - Insulin -- genetics KW - Peptides -- pharmacology KW - Cell Differentiation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69311921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Diabetes&rft.atitle=Glucagon-like+peptide+1+and+exendin-4+convert+pancreatic+AR42J+cells+into+glucagon-+and+insulin-producing+cells.&rft.au=Zhou%2C+J%3BWang%2C+X%3BPineyro%2C+M+A%3BEgan%2C+J+M&rft.aulast=Zhou&rft.aufirst=J&rft.date=1999-12-01&rft.volume=48&rft.issue=12&rft.spage=2358&rft.isbn=&rft.btitle=&rft.title=Diabetes&rft.issn=00121797&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-13 N1 - Date created - 1999-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense DNA-targeting protein kinase A-RIA subunit: a novel approach to cancer treatment. AN - 69307987; 10577386 AB - Enhanced expression of the RIa subunit of cAMP-dependent protein kinase type I (PKA-I) has been shown during carcinogenesis, in human cancer cell lines and in primary tumors. We demonstrate that the sequence-specific inhibition of RIa gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and tumors in mice. The loss of RI by the antisense results in rapid increase in the half-life of the competitor molecule, RII protein, via its stabilization in a holoenzyme complex (PKA-II) that insures depletion of PKA-I and sustained inhibition of tumor growth. RI antisense, which restrains tumor cell growth by turning on the signals for blockade of tumor cell survival, namely blockade of the tyrosine kinase signaling, cell cycle deregulation and apoptosis, provides a single gene-targeting approach to treatment of cancer. JF - Frontiers in bioscience : a journal and virtual library AU - Cho-Chung, Y S AU - Nesterova, M AU - Pepe, S AU - Lee, G R AU - Noguchi, K AU - Srivastava, R K AU - Srivastava, A R AU - Alper, O AU - Park, Y G AU - Lee, Y N AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - D898 EP - D907 VL - 4 SN - 1093-9946, 1093-9946 KW - Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit KW - 0 KW - Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - DNA, Antisense KW - PRKAR1A protein, human KW - PRKAR2A protein, human KW - PRKAR2B protein, human KW - Prkar1a protein, mouse KW - Prkar2a protein, mouse KW - Prkar2b protein, mouse KW - RNA, Messenger KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Animals KW - Apoptosis KW - Neoplasms, Experimental -- therapy KW - Neoplasms, Experimental -- genetics KW - Humans KW - Cell Differentiation -- genetics KW - Neoplasms, Experimental -- metabolism KW - Mice KW - Mice, Nude KW - Neoplasms, Experimental -- prevention & control KW - Neoplasms, Experimental -- pathology KW - RNA, Messenger -- biosynthesis KW - Protein-Tyrosine Kinases -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Drug Resistance, Neoplasm -- genetics KW - Cell Cycle -- genetics KW - Cell Division -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Neoplasms -- pathology KW - DNA, Antisense -- therapeutic use KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Cyclic AMP-Dependent Protein Kinases -- biosynthesis KW - Neoplasms -- prevention & control KW - DNA, Antisense -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- genetics KW - Neoplasms -- therapy KW - Neoplasms -- genetics KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69307987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.atitle=Antisense+DNA-targeting+protein+kinase+A-RIA+subunit%3A+a+novel+approach+to+cancer+treatment.&rft.au=Cho-Chung%2C+Y+S%3BNesterova%2C+M%3BPepe%2C+S%3BLee%2C+G+R%3BNoguchi%2C+K%3BSrivastava%2C+R+K%3BSrivastava%2C+A+R%3BAlper%2C+O%3BPark%2C+Y+G%3BLee%2C+Y+N&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=1999-12-01&rft.volume=4&rft.issue=&rft.spage=D898&rft.isbn=&rft.btitle=&rft.title=Frontiers+in+bioscience+%3A+a+journal+and+virtual+library&rft.issn=10939946&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-08 N1 - Date created - 1999-12-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity. AN - 69305226; 10572067 AB - This article examines differential expression and heterodimer formation of ErbB family members in tumorigenic and nontumorigenic human bronchial epithelial cells (HBECs). This cell system was developed previously as a model for lung adenocarcinoma by overexpression of c-erbB-2 in nontumorigenic, T antigen-immortalized HBECs. Earlier studies demonstrated that a tumorigenic clone from T antigen-immortalized nontumorigenic cells overexpressing ErbB-2 endogenously produced high levels of transforming growth factor (TGF)-alpha, and that reducing TGF-alpha by 93% eliminated tumorigenicity. In the present report, comparison of ErbB species between the tumorigenic cells (E6T) and their nontumorigenic derivatives (E6TA) demonstrated all four receptors in both cell types. However, in E6TA cells, ErbB-3 and -4 were present primarily in ErbB-1 heterodimers, suggesting that ErbB-1 is a preferred heterodimer partner within this cell system, expressing endogenous ErbB receptors and ligands and overexpressing ErbB-2. The ErbB-1/-2 species was present at high levels in E6T and absent in E6TA cells. Mitogen-activated protein kinase activity was elevated in E6T relative to E6TA. Elevated activity was eliminated by blocking surface expression of either ErbB-1 or ErbB-2. Endoplasmic reticulum trapping of ErbB-1 eliminated tumorigenicity, whereas ErbB-2 internalization was selected against during tumor formation. These data demonstrate the importance of TGF-alpha-mediated signaling through the ErbB-1/-2 heterodimer in development of the tumorigenic phenotype. This work further suggests that ErbB-3 and -4 species may also contribute to tumorigenic conversion and that their expression levels may be increased by signaling initiated by TGF-alpha. JF - American journal of respiratory cell and molecular biology AU - Fernandes, A M AU - Hamburger, A W AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 701 EP - 709 VL - 21 IS - 6 SN - 1044-1549, 1044-1549 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - ERBB4 protein, human KW - EC 2.7.10.1 KW - Erbb4 protein, mouse KW - Receptor, Epidermal Growth Factor KW - Receptor, ErbB-2 KW - Receptor, ErbB-3 KW - Receptor, ErbB-4 KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Index Medicus KW - Animals KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Mitogen-Activated Protein Kinases -- metabolism KW - Dimerization KW - Humans KW - Mice KW - Mice, Nude KW - Protein Binding KW - Receptor, ErbB-3 -- metabolism KW - Transfection KW - Lung KW - Flow Cytometry KW - Signal Transduction KW - Cell Line KW - Cell Transformation, Neoplastic KW - Epithelial Cells -- metabolism KW - Receptor, Epidermal Growth Factor -- metabolism KW - Receptor, ErbB-2 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69305226?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Dominance+of+ErbB-1+heterodimers+in+lung+epithelial+cells+overexpressing+ErbB-2.+Both+ErbB-1+and+ErbB-2+contribute+significantly+to+tumorigenicity.&rft.au=Fernandes%2C+A+M%3BHamburger%2C+A+W%3BGerwin%2C+B+I&rft.aulast=Fernandes&rft.aufirst=A&rft.date=1999-12-01&rft.volume=21&rft.issue=6&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-19 N1 - Date created - 2000-01-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial. AN - 69300035; 10576182 AB - To compare the efficacy and toxicity of topical vaginal 5-fluorouracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical dysplasia in human immunodeficiency virus (HIV)-infected women and to evaluate the association between baseline CD4 count and time to recurrence. In a phase III unmasked, randomized, multicenter, outpatient clinical trial, 101 HIV-positive women either received 6 months of biweekly treatment with vaginal 5-FU cream (2 g) or underwent 6 months of observation after standard excisional or ablative cervical treatment for cervical intraepithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end point being the time at which CIN of any grade recurred. Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Treatment with 5-FU was significantly associated with prolonged time to CIN development (P = .04). Observation subjects were more likely to have high-grade recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU treatment arm (P = .014), and disease recurred more quickly in observation subjects as well. Baseline CD4 count was related significantly to time to recurrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells/mm3 developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had received antiretroviral therapy than in antiretroviral therapy-naive subjects. There were no instances of grade 3 or 4 toxicity, and compliance with 5-FU treatment was generally good. Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence of cervical intraepithelial neoplasia in HIV-infected women. JF - Obstetrics and gynecology AU - Maiman, M AU - Watts, D H AU - Andersen, J AU - Clax, P AU - Merino, M AU - Kendall, M A AD - Adult AIDS Clinical Trials Group, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. mmaiman@siuh.edu Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 954 EP - 961 VL - 94 IS - 6 SN - 0029-7844, 0029-7844 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - Administration, Intravaginal KW - CD4 Lymphocyte Count KW - Female KW - Neoplasm Recurrence, Local -- prevention & control KW - Cervical Intraepithelial Neoplasia -- complications KW - Cervical Intraepithelial Neoplasia -- drug therapy KW - Uterine Cervical Neoplasms -- complications KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Uterine Cervical Dysplasia -- drug therapy KW - Cervical Intraepithelial Neoplasia -- immunology KW - Uterine Cervical Dysplasia -- immunology KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- therapeutic use KW - Uterine Cervical Neoplasms -- drug therapy KW - HIV Infections -- complications KW - HIV Infections -- immunology KW - Uterine Cervical Dysplasia -- complications KW - Uterine Cervical Neoplasms -- immunology KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69300035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Obstetrics+and+gynecology&rft.atitle=Vaginal+5-fluorouracil+for+high-grade+cervical+dysplasia+in+human+immunodeficiency+virus+infection%3A+a+randomized+trial.&rft.au=Maiman%2C+M%3BWatts%2C+D+H%3BAndersen%2C+J%3BClax%2C+P%3BMerino%2C+M%3BKendall%2C+M+A&rft.aulast=Maiman&rft.aufirst=M&rft.date=1999-12-01&rft.volume=94&rft.issue=6&rft.spage=954&rft.isbn=&rft.btitle=&rft.title=Obstetrics+and+gynecology&rft.issn=00297844&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-09 N1 - Date created - 1999-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point. AN - 69296426; 10570296 AB - Anti-Tac(Fv)-PE38, also called LMB-2, is a very active recombinant immunotoxin that has produced eight responses, including a durable clinical complete remission in a recently completed phase I trial of leukemias and lymphomas. Dose escalation was limited by liver toxicity. We have noted that the Fv of anti-Tac has an isoelectric point (pI) of 10.2. We hypothesize that the overall positive charge on the Fv portion of anti-Tac(Fv)-PE38 contributes to nonspecific binding to liver cells and results in dose-limiting liver toxicity. We have used a mouse model to investigate the basis of this toxicity and found that lowering the pI of the Fv of anti-Tac from 10.2 to 6. 82 by selective mutation of surface residues causes a 3-fold decrease in animal toxicity and hepatic necrosis. This change in pI did not significantly alter the CD25 binding affinity, the cytotoxic activity toward target cells, or antitumor activity, resulting in a 3-fold improvement in the therapeutic index. If this decreased toxicity occurs in humans, it should greatly increase the clinical utility of this immunotoxin. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Onda, M AU - Kreitman, R J AU - Vasmatzis, G AU - Lee, B AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 6072 EP - 6077 VL - 163 IS - 11 SN - 0022-1767, 0022-1767 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Antineoplastic Agents KW - B3(Fv)-PE38KDEL recombinant immunotoxin KW - Bacterial Toxins KW - Exotoxins KW - Immunoglobulin Fragments KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - immunoglobulin Fv KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Isoelectric Point KW - Mice KW - Mice, Nude KW - Structure-Activity Relationship KW - Recombinant Proteins -- toxicity KW - Liver -- drug effects KW - Toxicity Tests KW - Antineoplastic Agents -- toxicity KW - Neoplasms, Experimental -- drug therapy KW - Female KW - Exotoxins -- genetics KW - Immunotoxins -- toxicity KW - Antibodies, Neoplasm -- genetics KW - Immunoglobulin Fragments -- genetics KW - Exotoxins -- toxicity KW - Immunotoxins -- genetics KW - Mutation KW - Antibodies, Neoplasm -- toxicity KW - Immunoglobulin Fragments -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69296426?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Reduction+of+the+nonspecific+animal+toxicity+of+anti-Tac%28Fv%29-PE38+by+mutations+in+the+framework+regions+of+the+Fv+which+lower+the+isoelectric+point.&rft.au=Onda%2C+M%3BKreitman%2C+R+J%3BVasmatzis%2C+G%3BLee%2C+B%3BPastan%2C+I&rft.aulast=Onda&rft.aufirst=M&rft.date=1999-12-01&rft.volume=163&rft.issue=11&rft.spage=6072&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-20 N1 - Date created - 1999-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase Cdelta targets mitochondria, alters mitochondrial membrane potential, and induces apoptosis in normal and neoplastic keratinocytes when overexpressed by an adenoviral vector. AN - 69290260; 10567579 AB - Inactivation of protein kinase Cdelta (PKCdelta) is associated with resistance to terminal cell death in epidermal tumor cells, suggesting that activation of PKCdelta in normal epidermis may be a component of a cell death pathway. To test this hypothesis, we constructed an adenovirus vector carrying an epitope-tagged PKCdelta under a cytomegalovirus promoter to overexpress PKCdelta in normal and neoplastic keratinocytes. While PKCdelta overexpression was detected by immunoblotting in keratinocytes, the expression level of other PKC isozymes, including PKCalpha, PKCepsilon, PKCzeta, and PKCeta, did not change. Calcium-independent PKC-specific kinase activity increased after infection of keratinocytes with the PKCdelta adenovirus. Activation of PKCdelta by 12-O-tetradecanoylphorbol-13-acetate (TPA) at a nanomolar concentration was lethal to normal and neoplastic mouse and human keratinocytes overexpressing PKCdelta. Lethality was inhibited by PKC selective inhibitors, GF109203X and Ro-32-0432. TPA-induced cell death was apoptotic as evidenced by morphological criteria, TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, DNA fragmentation, and increased caspase activity. Subcellular fractionation indicated that PKCdelta translocated to a mitochondrial enriched fraction after TPA activation, and this finding was confirmed by confocal microscopy of cells expressing a transfected PKCdelta-green fluorescent protein fusion protein. Furthermore, activation of PKCdelta in keratinocytes altered mitochondrial membrane potential, as indicated by rhodamine-123 fluorescence. Mitochondrial inhibitors, rotenone and antimycin A, reduced TPA-induced cell death in PKCdelta-overexpressing keratinocytes. These results indicate that PKCdelta can initiate a death pathway in keratinocytes that involves direct interaction with mitochondria and alterations of mitochondrial function. JF - Molecular and cellular biology AU - Li, L AU - Lorenzo, P S AU - Bogi, K AU - Blumberg, P M AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Science, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 8547 EP - 8558 VL - 19 IS - 12 SN - 0270-7306, 0270-7306 KW - Isoenzymes KW - 0 KW - Mitogens KW - Recombinant Fusion Proteins KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - PRKCD protein, human KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-delta KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Mitogens -- pharmacology KW - Recombinant Fusion Proteins -- biosynthesis KW - Adenoviridae KW - Animals KW - Enzyme Activation KW - HeLa Cells KW - Humans KW - Gene Expression KW - Mice KW - Mice, Inbred BALB C KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Genetic Vectors KW - Recombinant Fusion Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Membrane Potentials KW - Intracellular Membranes -- physiology KW - Keratinocytes -- physiology KW - Mitochondria -- physiology KW - Keratinocytes -- drug effects KW - Isoenzymes -- biosynthesis KW - Protein Kinase C -- genetics KW - Apoptosis -- drug effects KW - Keratinocytes -- cytology KW - Protein Kinase C -- biosynthesis KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69290260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Protein+kinase+Cdelta+targets+mitochondria%2C+alters+mitochondrial+membrane+potential%2C+and+induces+apoptosis+in+normal+and+neoplastic+keratinocytes+when+overexpressed+by+an+adenoviral+vector.&rft.au=Clay%2C+T+M%3BCuster%2C+M+C%3BMcKee%2C+MD%3BParkhurst%2C+M%3BRobbins%2C+P+F%3BKerstann%2C+K%3BWunderlich%2C+J%3BRosenberg%2C+SA%3BNishimura%2C+MI&rft.aulast=Clay&rft.aufirst=T&rft.date=1999-02-01&rft.volume=162&rft.issue=3&rft.spage=1749&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1982 Jun;42(6):2344-9 [6122503] J Cell Biol. 1998 Mar 23;140(6):1485-95 [9508780] J Invest Dermatol. 1987 Jan;88(1):60-5 [2878959] Cancer Res. 1988 Jan 1;48(1):165-9 [3121168] Cancer Res. 1991 Sep 1;51(17):4677-84 [1678684] Mol Carcinog. 1992;6(1):18-25 [1380247] J Cell Biol. 1993 Jan;120(1):217-25 [7678013] Carcinogenesis. 1993 Feb;14(2):205-9 [8435862] J Biol Chem. 1993 Mar 25;268(9):6090-6 [8454583] J Biol Chem. 1993 Jul 25;268(21):15812-22 [8340406] J Biol Chem. 1993 Sep 25;268(27):20110-5 [8376369] J Invest Dermatol. 1993 Dec;101(6):858-63 [8245514] J Biol Chem. 1993 Dec 15;268(35):26079-81 [8253722] J Biol Chem. 1994 Jan 28;269(4):2349-52 [7507923] Cancer Res. 1994 Mar 1;54(5):1178-89 [8118803] Dev Dyn. 1994 Mar;199(3):176-88 [7517223] Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10732-6 [7938020] J Biol Chem. 1995 Apr 28;270(17):9991-10001 [7730383] Cell Growth Differ. 1995 Feb;6(2):149-57 [7756173] Cell Growth Differ. 1995 Apr;6(4):371-82 [7794805] Exp Cell Res. 1995 Jul;219(1):299-303 [7628546] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9112-6 [7568083] Methods Enzymol. 1995;254:3-20 [8531694] EMBO J. 1995 Dec 15;14(24):6148-56 [8557034] Blood. 1996 Mar 1;87(5):1990-6 [8634449] J Biol Chem. 1996 Mar 8;271(10):5325-31 [8621384] J Biol Chem. 1996 Sep 20;271(38):23512-9 [8798560] J Exp Med. 1996 Dec 1;184(6):2399-404 [8976194] Circ Res. 1998 Jun 1;82(10):1053-62 [9622158] J Investig Dermatol Symp Proc. 1996 Apr;1(2):136-42 [9627707] Mol Cell Biol. 1998 Sep;18(9):5199-207 [9710604] Mol Cell Biol. 1998 Sep;18(9):5263-71 [9710611] Science. 1998 Aug 28;281(5381):1309-12 [9721092] J Biol Chem. 1998 Sep 25;273(39):25436-42 [9738012] Carcinogenesis. 1998 Aug;19(8):1467-74 [9744544] Mol Cell Biol. 1998 Nov;18(11):6719-28 [9774685] Exp Gerontol. 1998 Sep;33(6):543-53 [9789732] Cell Signal. 1998 Sep;10(8):529-42 [9794251] J Biol Chem. 1998 Nov 6;273(45):29995-30002 [9792720] Mol Cell Biol. 1999 Apr;19(4):3086-94 [10082575] Eur J Biochem. 1999 Feb;259(3):555-64 [10092837] J Biol Chem. 1999 May 28;274(22):15389-94 [10336426] Cell. 1997 Nov 14;91(4):443-6 [9390553] Princess Takamatsu Symp. 1994;24:290-302 [8983083] J Biol Chem. 1997 Aug 22;272(34):21388-95 [9261153] Cell. 1997 Nov 28;91(5):627-37 [9393856] J Biol Chem. 1997 Dec 26;272(52):33338-43 [9407126] Br J Dermatol. 1997 Dec;137(6):883-9 [9470903] Oncogene. 1998 Feb 19;16(7):853-63 [9484776] Cancer Res. 1985 Oct;45(10):4864-70 [4027973] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Long-Term Effects of Witnessing Marital Violence for Women: The Contribution of Childhood Physical and Sexual Abuse AN - 61662617; 200003672 AB - Questionnaire data from 3l3 female undergraduates at Cornell U (Ithaca, NY) revealed that 9% reported having witnessed some type of physical conflict between their parents. Witnessing marital violence was associated with other family mental health risks, childhood physical & sexual abuse, & adult physical assaults by strangers. Women who witnessed marital violence reported more symptoms of posttraumatic stress disorder than other women, after family background & abuse variables were accounted for. Significant interactions between witnessing marital violence & childhood physical abuse were observed for measures of current social avoidance & predictability in partner relationships, indicating that the effects of witnessing marital violence depended on the presence of childhood abuse. Implications of these results for research & interventions are discussed. 6 Tables, 70 References. Adapted from the source document. JF - Journal of Family Violence AU - Feerick, Margaret M AU - Haugaard, Jeffrey J AD - Child Development & Behavior Branch, National Instit Child Health & Human Development, Bethesda, MD feerickm@mail.nih.gov Y1 - 1999/12// PY - 1999 DA - December 1999 SP - 377 EP - 398 VL - 14 IS - 4 SN - 0885-7482, 0885-7482 KW - Marital Relations KW - Undergraduate Students KW - Childhood Factors KW - Interpersonal Relations KW - Adult Development KW - Adolescent Development KW - Home Environment KW - New York KW - Family Violence KW - Females KW - Child Abuse KW - Child Sexual Abuse KW - article KW - 6143: child & family welfare UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61662617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocialservices&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Family+Violence&rft.atitle=Long-Term+Effects+of+Witnessing+Marital+Violence+for+Women%3A+The+Contribution+of+Childhood+Physical+and+Sexual+Abuse&rft.au=Feerick%2C+Margaret+M%3BHaugaard%2C+Jeffrey+J&rft.aulast=Feerick&rft.aufirst=Margaret&rft.date=1999-12-01&rft.volume=14&rft.issue=4&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=Journal+of+Family+Violence&rft.issn=08857482&rft_id=info:doi/ LA - English DB - Social Services Abstracts N1 - Date revised - 2007-05-01 N1 - Last updated - 2016-09-28 N1 - SubjectsTermNotLitGenreText - Family Violence; Childhood Factors; Females; Adult Development; Adolescent Development; Interpersonal Relations; Marital Relations; Child Sexual Abuse; Child Abuse; Home Environment; Undergraduate Students; New York ER - TY - JOUR T1 - Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates AN - 18181521; 5202486 AB - This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 x 10 super(9) or 1 x 10 super(8) plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent. JF - Cancer Gene Therapy AU - O'Connell, A C AU - Baccaglini, L AU - Fox, P C AU - O'Connell, B C AU - Kenshalo, D AU - Oweisy, H AU - Hoque, ATMS AU - Sun, D AU - Herscher, LL AU - Braddon, V R AU - Delporte, C AU - Baum, B J AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Building 10, Room 1N113, MSC-1190, Bethesda, MD 20892, USA, bruce_j_baumnih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 505 EP - 513 VL - 6 IS - 6 SN - 0929-1903, 0929-1903 KW - Primates KW - AdhAQP1 gene KW - aquaporin 1 KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Parotid gland KW - Salivary gland KW - Radiation KW - cDNA KW - Gene transfer KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18181521?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Gene+Therapy&rft.atitle=Safety+and+efficacy+of+adenovirus-mediated+transfer+of+the+human+aquaporin-1+cDNA+to+irradiated+parotid+glands+of+non-human+primates&rft.au=O%27Connell%2C+A+C%3BBaccaglini%2C+L%3BFox%2C+P+C%3BO%27Connell%2C+B+C%3BKenshalo%2C+D%3BOweisy%2C+H%3BHoque%2C+ATMS%3BSun%2C+D%3BHerscher%2C+LL%3BBraddon%2C+V+R%3BDelporte%2C+C%3BBaum%2C+B+J&rft.aulast=O%27Connell&rft.aufirst=A&rft.date=1999-12-01&rft.volume=6&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Cancer+Gene+Therapy&rft.issn=09291903&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-14 N1 - SubjectsTermNotLitGenreText - Primates; Radiation; Gene transfer; Salivary gland; Parotid gland; Gene therapy; cDNA ER - TY - JOUR T1 - Identification of Treponema pallidum Subspecies pallidum in a 200-Year-Old Skeletal Specimen AN - 18082541; 5155289 AB - Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, was detected in a 200-year-old skeletal specimen from Easter Island. An initial diagnosis of treponemal infection was confirmed by extensive purification of immunoglobulin that reacted strongly with T. pallidum antigen. Extracted DNA exhibited a single-base polymorphism that distinguished T.p. subsp. pallidum from 4 other human and nonhuman treponemes. Extensive precautions against contamination of the subject matter with modern treponemal DNA were employed, including analysis of archaeological and modern specimens in 2 geographically separate laboratories. Molecular determination of historical disease states by using skeletal material can significantly enhance our understanding of the pathology and spread of infectious diseases. JF - Journal of Infectious Diseases AU - Kolman, C J AU - Centurion-Lara, A AU - Lukehart, SA AU - Owsley, D W AU - Tuross, N AD - National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism/Laboratory of Neurogenetics, Rockville, MD, USA Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 2060 EP - 2063 VL - 180 IS - 6 SN - 0022-1899, 0022-1899 KW - Easter I. KW - Microbiology Abstracts B: Bacteriology KW - Disease spread KW - Treponema pallidum KW - Syphilis KW - Skeleton KW - J 02849:Sexually-transmitted diseases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18082541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=Identification+of+Treponema+pallidum+Subspecies+pallidum+in+a+200-Year-Old+Skeletal+Specimen&rft.au=Kolman%2C+C+J%3BCenturion-Lara%2C+A%3BLukehart%2C+SA%3BOwsley%2C+D+W%3BTuross%2C+N&rft.aulast=Kolman&rft.aufirst=C&rft.date=1999-12-01&rft.volume=180&rft.issue=6&rft.spage=2060&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Treponema pallidum; Syphilis; Skeleton; Disease spread ER - TY - JOUR T1 - Clinical Scenarios II: Syndromes with Abnormal Peritoneal Response AN - 17673740; 4750900 AB - The normal peritoneal response to microorganisms is characterized by hyperemia, exudation of protein-rich fluid into the peritoneal cavity and marked influx of neutrophils, universally known as peritonitis. Under favorable circumstances for the host, peritoneal and systemic defense mechanisms can remove infection from the peritoneal cavity (resolution) or at least manage to contain infection (intra-abdominal abscess). The normal peritoneal response to infection may be altered by local peritoneal and systemic factors resulting in a non-efficient mechanism that interferes with the ability of the host to eradicate infection from the peritoneal cavity or further damage the peritoneal interface. JF - Sepsis AU - Fiuza, C AD - CCMD/CC. National Institutes of Health. Bldg 10, RM 4d43. 10 Center Drive MSC-1662. Bethesda, MD 20892-1662, USA, cfiuza@mail.cc.nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 335 EP - 344 VL - 3 IS - 4 SN - 1385-0229, 1385-0229 KW - Microbiology Abstracts B: Bacteriology KW - Peritonitis KW - Peritoneum KW - Immune response KW - Peritoneal diseases KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17673740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Analgesic+efficacy+and+pharmacokinetics+of+ketoprofen+administered+into+a+surgical+site.&rft.au=Dionne%2C+R+A%3BGordon%2C+S+M%3BTahara%2C+M%3BRowan%2C+J%3BTroullos%2C+E&rft.aulast=Dionne&rft.aufirst=R&rft.date=1999-02-01&rft.volume=39&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Peritoneum; Peritonitis; Peritoneal diseases; Immune response ER - TY - JOUR T1 - Challenges to retrospective exposure assessment AN - 17591293; 4664446 AB - Retrospective exposure assessment has become a crucial component in the interpretation of occupational epidemiologic results. Many advances have been made over the last 2 decades, but substantial progress is still necessary to reduce the misclassification of exposure. The efforts needed include evaluating the validity and reliability of assessment methods, better documentation of the methods, use of exposure determinants to estimate exposure levels more accurately and reliably, and an increase in the understanding of industrial hygiene and biological measurement data and questionnaires, their limitations, and how to use them best. In addition, better characterization of exposures is necessary. This need includes evaluating dermal and ingestion hazards, incorporating nonoccupational sources of exposures, particularly hobbies, evaluating the effect of multiple chemicals, and exploring different exposure metrics. JF - Scandinavian Journal of Work, Environment & Health AU - Stewart, P AD - Occupational Epidemiology Branch, National Cancer Institute, EPS 8102, 6120 Executive Blvd., Rockville, Maryland, 20892, USA, stewartt@epndce.nci.nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 505 EP - 510 VL - 25 IS - 6 SN - 0355-3140, 0355-3140 KW - Health & Safety Science Abstracts KW - Chemicals KW - Epidemiology KW - Dose-response effects KW - Occupational exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17591293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Challenges+to+retrospective+exposure+assessment&rft.au=Stewart%2C+P&rft.aulast=Stewart&rft.aufirst=P&rft.date=1999-12-01&rft.volume=25&rft.issue=6&rft.spage=505&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Epidemiology; Dose-response effects; Chemicals ER - TY - JOUR T1 - Reduction of Furin-Nicked Pseudomonas Exotoxin A: An Unfolding Story AN - 17500243; 4685159 AB - Upon entering mammalian cells, Pseudomonas exotoxin A (PE) is proteolytically processed by furin to produce an N-terminal fragment of 28 kDa and a C-terminal fragment of 37 kDa. Cleavage is followed by the reduction of a key disulfide bond (cysteines 265-287). This combination of proteolysis and reduction releases the 37 kDa C-terminal fragment, which then translocates to the cytosol where it ADP-ribosylates elongation factor 2 and inhibits protein synthesis. To investigate toxin reduction, furin-nicked PE or a hypercleavable mutant, PEW281A, was subjected to various treatments and then analyzed for fragment production. Reduction was evident only when unfolding conditions and a reducing agent were applied. Thermal unfolding of PE, as evidenced by changes in alpha -helical content and increased sensitivity to trypsin, rendered nicked toxin susceptible to protein disulfide isomerase- (PDI-) mediated reduction. When subcellular fractions from toxin-sensitive cells were incubated with nicked PE, toxin unfolding and reducing activities were present in the membrane fraction but not the soluble fraction. These data indicate that PE reduction is a two-step process: unfolding that allows access to the Cys265-287 disulfide bond, followed by reduction of the sulfur-sulfur bond by PDI or a PDI-like enzyme. With regard to cellular processing, we propose that the toxin's three-dimensional structure retains a "closed" conformation that restricts solvent access to the Cys265-287 disulfide bond until after a cell-mediated unfolding event. JF - Biochemistry (Washington) AU - McKee, M L AU - FitzGerald, D J AD - Biotherapy Section, Laboratory of Molecular Biology, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA, djpf@helix.nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 16507 EP - 16513 VL - 38 IS - 50 SN - 0006-2960, 0006-2960 KW - exotoxin A KW - Microbiology Abstracts B: Bacteriology KW - Protein folding KW - Disulfide bonds KW - Pseudomonas KW - Tertiary structure KW - Translocation KW - J 02822:Biosynthesis and physicochemical properties UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17500243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Reduction+of+Furin-Nicked+Pseudomonas+Exotoxin+A%3A+An+Unfolding+Story&rft.au=McKee%2C+M+L%3BFitzGerald%2C+D+J&rft.aulast=McKee&rft.aufirst=M&rft.date=1999-12-01&rft.volume=38&rft.issue=50&rft.spage=16507&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi991308%2B LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas; Tertiary structure; Translocation; Protein folding; Disulfide bonds DO - http://dx.doi.org/10.1021/bi991308+ ER - TY - JOUR T1 - Disparate phylogeographic patterns of molecular genetic variation in four closely related South American small cat species AN - 17490262; 4679125 AB - Tissue specimens from four species of Neotropical small cats (Oncifelis geoffroyi, N = 38; O. guigna, N = 6; Leopardus tigrinus, N = 32; Lynchailurus colocolo, N = 22) collected from throughout their distribution were examined for patterns of DNA sequence variation using three mitochondrial genes, 16S rRNA, ATP8, and NADH-5. Patterns between and among O. guigna and O. geoffroyi individuals were assessed further from size variation at 20 microsatellite loci. Phylogenetic analyses using mitochondrial DNA sequences revealed monophyletic clustering of the four species, plus evidence of natural hybridization between L. tigrinus and L. colocolo in areas of range overlap and discrete population subdivisions reflecting geographical isolation. Several commonly accepted subspecies partitions were affirmed for L. colocolo, but not for O. geoffroyi. The lack of geographical substructure in O. geoffroyi was recapitulated with the microsatellite data, as was the monophyletic clustering of O. guigna and O. geoffroyi individuals. L. tigrinus forms two phylogeographic clusters which correspond to L.t. oncilla (from Costa Rica) and L.t. guttula (from Brazil) and which have mitochondrial DNA (mtDNA) genetic distance estimates comparable to interspecific values between other ocelot lineage species. Using feline-specific calibration rates for mitochondrial DNA mutation rates, we estimated that extant lineages of O. guigna diverged 0.4 million years ago (Ma), compared with 1.7 Ma for L. colocolo, 2.0 Ma for O. geoffroyi, and 3.7 Ma for L. tigrinus. JF - Molecular Ecology AU - Johnson, W E AU - Slattery, J P AU - Eizirik, E AU - Kim, J-H AU - Raymond, M M AU - Bonacic, C AU - Cambre, R AU - Crawshaw, P AU - Nunes, A AU - Seuanez, H N AU - Moreira, MAM AU - Seymour, K L AU - Simon, F AU - Swanson, W AU - O'Brien, S J AD - Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702-1201, USA, johnsonw@ncifcrf.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - S79 EP - S94 VL - 8 IS - 12 SN - 0962-1083, 0962-1083 KW - cats KW - ATP8 gene KW - NADH-8 gene KW - rRNA 16S KW - Ecology Abstracts; Genetics Abstracts KW - Phylogeny KW - Geographical distribution KW - Leopardus tigrinus KW - Biogeography KW - Oncifelis geoffroyi KW - Microsatellites KW - Genetic diversity KW - Lynchailurus colocolo KW - Ecological genetics KW - Population genetics KW - Mitochondrial DNA KW - Oncifelis guigna KW - Genetic distance KW - D 04672:Mammals KW - G 07405:Carnivora KW - G 07290:Population genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17490262?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Secondary+leukemia+or+myelodysplastic+syndrome+after+treatment+with+epipodophyllotoxins.&rft.au=Smith%2C+M+A%3BRubinstein%2C+L%3BAnderson%2C+J+R%3BArthur%2C+D%3BCatalano%2C+P+J%3BFreidlin%2C+B%3BHeyn%2C+R%3BKhayat%2C+A%3BKrailo%2C+M%3BLand%2C+V+J%3BMiser%2C+J%3BShuster%2C+J%3BVena%2C+D&rft.aulast=Smith&rft.aufirst=M&rft.date=1999-02-01&rft.volume=17&rft.issue=2&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Oncifelis geoffroyi; Oncifelis guigna; Leopardus tigrinus; Lynchailurus colocolo; Population genetics; Biogeography; Genetic diversity; Mitochondrial DNA; Microsatellites; Genetic distance; Ecological genetics; Phylogeny; Geographical distribution ER - TY - JOUR T1 - Juvenile guanaco survival: management and conservation implications AN - 17484001; 4675116 AB - 1. The Chilean National Forestry and Park Service is striving to implement a guanaco management programme of sustained-yield use. To achieve this, the rate, variation and causes of juvenile guanaco mortality must be understood thoroughly. Therefore, we monitored the survival of 409 radio-collared juvenile guanacos in Torres del Paine National Park, Chile, from 1991 to 1996. 2. The Kaplan-Meier product limit estimator of survival for staggered entry was calculated, and survival rates between juvenile males and females and among years were compared using the LIFETEST procedure in SAS. The Cox proportional hazards model was used to relate mortality rate to explanatory variables such as juvenile sex, birth weight, adult female aggression towards researchers during the capture and tagging of newborns, population density, and mean monthly winter snowfall. 3. Mean juvenile survival rate (S) was 0 times 38, but varied between 0 times 31 and 0 times 55. Survival rates between the sexes were not significantly different, although male survival was lower than that of females. Mortality rate was highest during the first 14 days after birth. Most deaths occurred between birth and 7 months of age. 4. The risk of mortality increased by almost 6% with every 1 cm increase in winter snowfall, whereas the risk of mortality decreased by almost 24% as adult female aggression increased towards researchers. 5. Current management objectives are aimed at the implementation of a rational harvest of guanacos on the Chilean side of the island of Tierra del Fuego. Our results provide improved and updated estimates of juvenile guanaco survival and will aid in the modelling of harvest rates of guanacos in southern Chile. Future proposed harvests from wild populations in southern Chile need to consider the rate and variation of this critical life-history parameter. JF - Journal of Applied Ecology AU - Sarno, R J AU - Clark, W R AU - Bank AU - Prexl, W S AU - Behl, MJ AU - Johnson, W E AU - Franklin, W L AD - Laboratory of Genomic Diversity, FCRDC/NCI, Building 560, Room 11-84, Frederick, MD 21702-1201, USA, rjsarno@mail.ncifcrf.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 937 EP - 945 VL - 36 IS - 6 SN - 0021-8901, 0021-8901 KW - Chile KW - Ecology Abstracts KW - Management KW - National parks KW - Conservation KW - Survival KW - Lama guanicoe KW - D 04700:Management UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17484001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Law+and+Human+Behavior&rft.atitle=The+alleged+%E2%80%9CFerguson+Effect%E2%80%9D+and+police+willingness+to+engage+in+community+partnership&rft.au=Wolfe%2C+Scott+E.%3BNix%2C+Justin&rft.aulast=Wolfe&rft.aufirst=Scott&rft.date=2016-02-01&rft.volume=40&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Law+and+Human+Behavior&rft.issn=01477307&rft_id=info:doi/10.1037%2Flhb0000164 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lama guanicoe; Survival; Management; Conservation; National parks DO - http://dx.doi.org/10.1046/j.1365-2664.1999.00449.x ER - TY - JOUR T1 - Replacement of the F and G Proteins of Respiratory Syncytial Virus (RSV) Subgroup A with Those of Subgroup B Generates Chimeric Live Attenuated RSV Subgroup B Vaccine Candidates AN - 17463776; 4673433 AB - Human respiratory syncytial virus (RSV) exists as two antigenic subgroups, A and B, both of which should be represented in a vaccine. The F and G glycoproteins are the major neutralization and protective antigens, and the G protein in particular is highly divergent between the subgroups. The existing system for reverse genetics is based on the A2 strain of RSV subgroup A, and most efforts to develop a live attenuated RSV vaccine have focused on strain A2 or other subgroup A viruses. In the present study, the development of a live attenuated subgroup B component was expedited by the replacement of the F and G glycoproteins of recombinant A2 virus with their counterparts from the RSV subgroup B strain B1. This gene replacement was initially done for wild-type (wt) recombinant A2 virus to create a wt AB chimeric virus and then for a series of A2 derivatives which contain various combinations of A2- derived attenuating mutations located in genes other than F and G. The wt AB virus replicated in cell culture with an efficiency which was comparable to that of the wt A2 and B1 parents. AB viruses containing temperature-sensitive mutations in the A2 background exhibited levels of temperature sensitivity in vitro which were similar to those of A2 viruses bearing the same mutations. In chimpanzees, the replication of the wt AB chimera was intermediate between that of the A2 and B1 wt viruses and was accompanied by moderate rhinorrhea, as previously seen in this species. An AB chimeric virus, rABcp248/404/1030, which was constructed to contain a mixture of attenuating mutations derived from two different biologically attenuated A2 viruses, was highly attenuated in both the upper and lower respiratory tracts of chimpanzees. This attenuated AB chimeric virus was immunogenic and conferred a high level of resistance on chimpanzees to challenge with wt AB virus. The rABcp248/404/1030 chimeric virus is a promising vaccine candidate for RSV subgroup B and will be evaluated next in humans. Furthermore, these results suggest that additional attenuating mutations derived from strain A2 can be inserted into the A2 background of the recombinant chimeric AB virus as necessary to modify the attenuation phenotype in a reasonably predictable manner to achieve an optimal balance between attenuation and immunogenicity in a virus bearing the subgroup B antigenic determinants. JF - Journal of Virology AU - Whitehead, S S AU - Hill, M G AU - Firestone, CY AU - Claire AU - Elkins, W R AU - Murphy, B R AU - Collins, P L AD - LID, NIAID, 7 Center Dr., MSC 0720, Bethesda, MD 20892-0720, sswhitehead@nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 9773 EP - 9780 VL - 73 IS - 12 SN - 0022-538X, 0022-538X KW - Immunogenicity KW - gene replacement KW - subgroup B KW - chimpanzees KW - Respiratory syncytial virus KW - double prime F protein KW - double prime G protein KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - G protein KW - F protein KW - ^AF protein KW - ^AG protein KW - Attenuation KW - Chimeras KW - Antigens KW - Vaccines KW - Glycoproteins KW - W3 33365:Vaccines (other) KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17463776?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Replacement+of+the+F+and+G+Proteins+of+Respiratory+Syncytial+Virus+%28RSV%29+Subgroup+A+with+Those+of+Subgroup+B+Generates+Chimeric+Live+Attenuated+RSV+Subgroup+B+Vaccine+Candidates&rft.au=Whitehead%2C+S+S%3BHill%2C+M+G%3BFirestone%2C+CY%3BClaire%3BElkins%2C+W+R%3BMurphy%2C+B+R%3BCollins%2C+P+L&rft.aulast=Whitehead&rft.aufirst=S&rft.date=1999-12-01&rft.volume=73&rft.issue=12&rft.spage=9773&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiratory syncytial virus; Glycoproteins; Chimeras; Vaccines; Attenuation; Antigens; Immunogenicity ER - TY - JOUR T1 - Structure and Function of the Tryptophan Synthase alpha sub(2) beta sub(2) Complex. Roles of beta Subunit Histidine 86 AN - 17461078; 4666011 AB - To probe the structural and functional roles of active-site residues in the tryptophan synthase alpha sub(2) beta sub(2) complex from Salmonella typhimurium, we have determined the effects of mutation of His super(86) in the beta subunit. His super(86) is located adjacent to beta subunit Lys super(87), which forms an internal aldimine with the pyridoxal phosphate and catalyzes the abstraction of the alpha -proton of L-serine. The replacement of His super(86) by leucine (H86L) weakened pyridoxal phosphate binding similar to 20-fold and abolished the circular dichroism signals of the bound coenzyme and of a reaction intermediate. Correlation of these results with previous crystal structures indicates that beta -His super(86) plays a structural role in binding pyridoxal phosphate and in stabilizing the correct orientation of pyridoxal phosphate in the active site of the beta subunit. The H86L mutation also altered the pH profiles of absorbance and fluorescence signals and shifted the pH optimum for the synthesis of L-tryptophan from pH 7.5 to 8.8. We propose that the interaction of His super(86) with the phosphate of pyridoxal phosphate and with Lys super(87) lowers the pKa of Lys super(87) in the wild-type alpha sub(2) beta sub(2) complex and thereby facilitates catalysis by Lys super(87) in the physiological pH range. JF - Journal of Biological Chemistry AU - Ro, H AU - Miles, E W AD - Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-0830 Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 36439 EP - 36445 VL - 274 IS - 51 SN - 0021-9258, 0021-9258 KW - mutagenesis KW - tryptophan synthase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Salmonella typhimurium KW - J 02728:Enzymes KW - N 14681:Mutagenesis techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17461078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Structure+and+Function+of+the+Tryptophan+Synthase+alpha+sub%282%29+beta+sub%282%29+Complex.+Roles+of+beta+Subunit+Histidine+86&rft.au=Ro%2C+H%3BMiles%2C+E+W&rft.aulast=Ro&rft.aufirst=H&rft.date=1999-12-01&rft.volume=274&rft.issue=51&rft.spage=36439&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.274.51.36439 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhimurium DO - http://dx.doi.org/10.1074/jbc.274.51.36439 ER - TY - JOUR T1 - Cholesteryl Ester Transfer Protein Corrects Dysfunctional High Density Lipoproteins and Reduces Aortic Atherosclerosis in Lecithin Cholesterol Acyltransferase Transgenic Mice AN - 17458530; 4666069 AB - Expression of human lecithin cholesterol acyltransferase (LCAT) in mice (LCAT-Tg) leads to increased high density lipoprotein (HDL) cholesterol levels but paradoxically, enhanced atherosclerosis. We have hypothesized that the absence of cholesteryl ester transfer protein (CETP) in LCAT-Tg mice facilitates the accumulation of dysfunctional HDL leading to impaired reverse cholesterol transport and the development of a pro-atherogenic state. To test this hypothesis we cross-bred LCAT-Tg with CETP-Tg mice. On both regular chow and high fat, high cholesterol diets, expression of CETP in LCAT-Tg mice reduced total cholesterol (-39% and -13%, respectively; p < 0.05), reflecting a decrease in HDL cholesterol levels. CETP normalized both the plasma clearance of [ super(3)H]cholesteryl esters ([ super(3)H]CE) from HDL (fractional catabolic rate in days super(-1): LCAT-Tg = 3.7 plus or minus 0.34, LCATxCETP-Tg = 6.1 plus or minus 0.16, and controls = 6.4 plus or minus 0.16) as well as the liver uptake of [ super(3)H]CE from HDL (LCAT-Tg = 36%, LCATxCETP-Tg = 65%, and controls = 63%) in LCAT-Tg mice. On the pro-atherogenic diet the mean aortic lesion area was reduced by 41% in LCATxCETP-Tg (21.2 plus or minus 2.0 mu m super(2) x 10 super(3)) compared with LCAT-Tg mice (35.7 plus or minus 2.0 mu m super(2) x 10 super(3); p < 0.001). Adenovirus-mediated expression of scavenger receptor class B (SR-BI) failed to normalize the plasma clearance and liver uptake of [ super(3)H]CE from LCAT-Tg HDL. Thus, the ability of SR-BI to facilitate the selective uptake of CE from LCAT-Tg HDL is impaired, indicating a potential mechanism leading to impaired reverse cholesterol transport and atherosclerosis in these animals. We conclude that CETP expression reduces atherosclerosis in LCAT-Tg mice by restoring the functional properties of LCAT-Tg mouse HDL and promoting the hepatic uptake of HDL-CE. These findings provide definitive in vivo evidence supporting the proposed anti-atherogenic role of CETP in facilitating HDL-mediated reverse cholesterol transport and demonstrate that CETP expression is beneficial in pro-atherogenic states that result from impaired reverse cholesterol transport. JF - Journal of Biological Chemistry AU - Foeger, B AU - Chase, M AU - Amar, MJ AU - Vaisman, B L AU - Shamburek, R D AU - Paigen, B AU - Fruchart-Najib, J AU - Paiz, JA AU - Koch, CA AU - Hoyt, R F AU - Brewer Jr, HB AU - Santamarina-Fojo, S AD - Molecular Disease Branch and Laboratory of Animal Medicine/Surgery, NHLBI, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 36912 EP - 36920 VL - 274 IS - 52 SN - 0021-9258, 0021-9258 KW - Transgenic mice KW - Adenovirus KW - Cholesteryl ester transfer protein KW - cholesteryl ester transfer protein KW - phosphatidylcholine-sterol acyltransferase KW - scavenger receptor class B KW - scavenger receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Phosphatidylcholine-sterol O-acyltransferase KW - Lipoproteins (high density) KW - Cholesterol KW - Arteriosclerosis KW - W3 33056:Animal models of human disease KW - G 07444:Animal models KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17458530?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Neural+Modeling+and+Functional+Brain+Imaging%3A+The+Interplay+between+the+Data-Fitting+and+Simulation+Approaches&rft.au=Horwitz%2C+Barry%3BGlabus%2C+Michael+F&rft.aulast=Horwitz&rft.aufirst=Barry&rft.date=1999-02-01&rft.volume=43&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2FS0074-7742%2805%2966009-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Arteriosclerosis; Lipoproteins (high density); Cholesterol; Phosphatidylcholine-sterol O-acyltransferase DO - http://dx.doi.org/10.1074/jbc.274.52.36912 ER - TY - JOUR T1 - Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease AN - 17452865; 4664368 AB - Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune disease. JF - Nature Medicine AU - Hemmer, B AU - Gran, B AU - Zhao, Y AU - Marques, A AU - Pascal, J AU - Tzou, A AU - Kondo, T AU - Cortese, I AU - Bielekova, B AU - Straus, SE AU - McFarland, H F AU - Houghten, R AU - Simon, R AU - Pinilla, C AU - Martin, R AD - Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5B-16, 10 Center DR MSC 1400, Bethesda, Maryland 20892-1400, USA, Roland_Martin@nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 1375 EP - 1382 VL - 5 IS - 12 SN - 1078-8956, 1078-8956 KW - epitopes KW - immunology KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Infectious diseases KW - Autoimmune diseases KW - Lymphocytes T KW - Tumors KW - Vaccines KW - Lyme disease KW - J 02833:Immune response and immune mechanisms KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17452865?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Identification+of+candidate+T-cell+epitopes+and+molecular+mimics+in+chronic+Lyme+disease&rft.au=Hemmer%2C+B%3BGran%2C+B%3BZhao%2C+Y%3BMarques%2C+A%3BPascal%2C+J%3BTzou%2C+A%3BKondo%2C+T%3BCortese%2C+I%3BBielekova%2C+B%3BStraus%2C+SE%3BMcFarland%2C+H+F%3BHoughten%2C+R%3BSimon%2C+R%3BPinilla%2C+C%3BMartin%2C+R&rft.aulast=Hemmer&rft.aufirst=B&rft.date=1999-12-01&rft.volume=5&rft.issue=12&rft.spage=1375&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2F70946 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lymphocytes T; Lyme disease; Vaccines; Infectious diseases; Tumors; Autoimmune diseases DO - http://dx.doi.org/10.1038/70946 ER - TY - JOUR T1 - Occupational cancer epidemiology in the coming decades AN - 17449146; 4664445 AB - Occupational studies have identified many of the established chemical carcinogens. Studies in the next millennium will be needed to identify the hazardous agents in occupations known to have high cancer rates, to assess human risks from animal carcinogens that have not been well evaluated epidemiologically, to provide information on women and minorities, to evaluate interactions with genetic factors and other risk factors, to contribute to our understanding of risks from the spread of chemicals from the workplace to the general environment, and to identify mechanisms of cancer. The traditional retrospective cohort design will be insufficient to meet these needs. Population-based case-control, nested case-control, prospective cohorts, and cross-sectional designs will assume more important roles because of the need to collect information on nonoccupational risk factors and biological tissues. Improvement in the assessment of quantitative exposures is needed for the efficient evaluation of interactions between occupational exposures, genetic factors, and nonoccupational exposures. JF - Scandinavian Journal of Work, Environment & Health AU - Blair, A AU - Rothman, N AU - Zahm, SH AD - National Cancer Institute, Executive Plaza South, Room 8118, Bethesda, MD 20892, USA Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 491 EP - 497 VL - 25 IS - 6 SN - 0355-3140, 0355-3140 KW - Health & Safety Science Abstracts KW - Chemicals KW - Risk assessment KW - Cancer KW - Epidemiology KW - occupational diseases KW - Occupational exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17449146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Occupational+cancer+epidemiology+in+the+coming+decades&rft.au=Blair%2C+A%3BRothman%2C+N%3BZahm%2C+SH&rft.aulast=Blair&rft.aufirst=A&rft.date=1999-12-01&rft.volume=25&rft.issue=6&rft.spage=491&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - occupational diseases; Occupational exposure; Cancer; Epidemiology; Risk assessment; Chemicals ER - TY - JOUR T1 - Searching for drug targets in microbial genomes AN - 17446791; 4659036 AB - Comparative analysis of the complete genome sequences of 10 bacterial pathogens available in the public databases offers the first insights into the drug discovery approaches of the near future. Genes that are conserved in different genomes often turn out to be essential, which makes them attractive targets for new broad-spectrum antibiotics. Subtractive genome analysis reveals the genes that are conserved in all or most of the pathogenic bacteria but not in eukaryotes; these are the most obvious candidates for drug targets. Species-specific genes, on the other hand, may offer the possibility to design drugs against a particular, narrow group of pathogens. JF - Current Opinion in Biotechnology AU - Galperin, MY AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, galperin@ncbi.nlm.nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 571 EP - 578 VL - 10 IS - 6 SN - 0958-1669, 0958-1669 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Genomes KW - Databases KW - Reviews KW - Microorganisms KW - Pathogens KW - Drugs KW - W 30965:Miscellaneous, Reviews KW - W3 33000:General topics and reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17446791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Biotechnology&rft.atitle=Searching+for+drug+targets+in+microbial+genomes&rft.au=Galperin%2C+MY%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=1999-12-01&rft.volume=10&rft.issue=6&rft.spage=571&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Biotechnology&rft.issn=09581669&rft_id=info:doi/10.1016%2FS0958-1669%2899%2900035-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genomes; Drugs; Databases; Reviews; Microorganisms; Pathogens DO - http://dx.doi.org/10.1016/S0958-1669(99)00035-X ER - TY - JOUR T1 - Liposome-mediated gene transfer into human basal cell carcinoma AN - 17442356; 4658145 AB - Direct intralesional injection of DNA encoding interferon- alpha 2 (IFN- alpha 2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN- alpha 2 using this method resulted in sustained production of IFN- alpha 2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN- alpha protein may therefore be applicable to the treatment of cutaneous BCC. JF - Gene Therapy AU - Hottiger, MO AU - Dam, T N AU - Nickoloff, B J AU - Johnson, T M AU - Nabel, G J AD - Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 1929 EP - 1935 VL - 6 IS - 12 SN - 0969-7128, 0969-7128 KW - man KW - mice KW - alpha -Interferon KW - basal cells KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - ^a-Interferon KW - Gene therapy KW - Gene transfer KW - Major histocompatibility complex KW - Liposomes KW - a-Interferon KW - Carcinoma KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17442356?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Liposome-mediated+gene+transfer+into+human+basal+cell+carcinoma&rft.au=Hottiger%2C+MO%3BDam%2C+T+N%3BNickoloff%2C+B+J%3BJohnson%2C+T+M%3BNabel%2C+G+J&rft.aulast=Hottiger&rft.aufirst=MO&rft.date=1999-12-01&rft.volume=6&rft.issue=12&rft.spage=1929&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Carcinoma; Liposomes; a-Interferon; Major histocompatibility complex; Gene therapy ER - TY - JOUR T1 - DNA-binding proteins and evolution of transcription regulation in the archaea AN - 17440450; 4658954 AB - Likely DNA-binding domains in archaeal proteins were analyzed using sequence profile methods and available structural information. It is shown that all archaea encode a large number of proteins containing the helix-turn-helix (HTH) DNA-binding domains whose sequences are much more similar to bacterial HTH domains than to eukaryotic ones, such as the PAIRED, POU and homeodomains. The predominant class of HTH domains in archaea is the winged-HTH domain. The number and diversity of HTH domains in archea is comparable to that seen in bacteria. The HTH domain in archaea combines with a variety of other domains that include replication system components, such as MCM proteins, translation system components, such as the alpha -subunit of phenylalanyl-tRNA synthetase, and several metabolic enzymes. The majority of the archaeal HTH-containing proteins are predicted to be gene/operon-specific transcriptional regulators. This apparent bacterial-type mode of transcription regulation is in sharp contrast to the eukaryote-like layout of the core transcription machinery in the archaea. In addition to the predicted bacterial-type transcriptional regulators, the HTH domain is conserved in archaeal and eukaryotic core transcription factors, such as TFIIB, TFIIE- alpha and MBF1. MBF1 is the only highly conserved, classical HTH domain that is vertically inherited in all archaea and eukaryotes. In contrast, while eukaryotic TFIIB and TFIIE- alpha possess forms of the HTH domain that are divergent in sequence, their archaeal counterparts contain typical HTH domains. It is shown that, besides the HTH domain, archaea encode unexpectedly large numbers of two other predicted DNA-binding domains, namely the Arc/MetJ domain and the Znribbon. The core transcription regulators in archaea and eukaryotes (TFIIB/TFB, TFIIE- alpha and MBF1) and in bacteria (the sigma factors) share no similarity beyond the presence of distinct HTH domains. Thus HTH domains might have been independently recruited for a role in transcription regulation in the bacterial and archaeal/eukaryotic lineages. During subsequent evolution, the similarity between archaeal and bacterial gene/operon transcriptional regulators might have been established and maintained through multiple horizontal gene transfer events. JF - Nucleic Acids Research AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@golem.nlm.nih.gov Y1 - 1999/12/01/ PY - 1999 DA - 1999 Dec 01 SP - 4658 EP - 4670 VL - 27 IS - 23 SN - 0305-1048, 0305-1048 KW - HTH domain KW - bacteria KW - MBF1 protein KW - MCM protein KW - TFB protein KW - phenylalanine-tRNA ligase KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Transcription initiation factor TFIIB KW - DNA-binding protein KW - Transcription initiation factor TFIIE KW - Gene regulation KW - Transcription factors KW - Sigma factor KW - J 02725:DNA KW - N 14662:Gene regulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17440450?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+Acids+Research&rft.atitle=DNA-binding+proteins+and+evolution+of+transcription+regulation+in+the+archaea&rft.au=Aravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Aravind&rft.aufirst=L&rft.date=1999-12-01&rft.volume=27&rft.issue=23&rft.spage=4658&rft.isbn=&rft.btitle=&rft.title=Nucleic+Acids+Research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA-binding protein; Transcription factors; Transcription initiation factor TFIIB; Transcription initiation factor TFIIE; Sigma factor; Gene regulation ER - TY - JOUR T1 - Cellobiose-6-Phosphate Hydrolase (CelF) of Escherichia coli: Characterization and Assignment to the Unusual Family 4 of Glycosylhydrolases AN - 17341782; 4627065 AB - The gene celF of the cryptic cel operon of Escherichia coli has been cloned, and the encoded 6-phospho- beta -glucosidase (cellobiose-6-phosphate [6P] hydrolase; CelF [EC 3.2.1.86]) has been expressed and purified in a catalytically active state. Among phospho- beta - glycosidases, CelF exhibits unique requirements for a divalent metal ion and NAD super(+) for activity and, by sequence alignment, is assigned to family 4 of the glycosylhydrolase superfamily. CelF hydrolyzed a variety of P- beta -glucosides, including cellobiose- 6P, salicin-6P arbutin-6P, gentiobiose-6P, methyl- beta -glucoside- 6P, and the chromogenic analog, p-nitrophenyl- beta -D- glucopyranoside-6P. In the absence of a metal ion and NAD super(+), purified CelF was rapidly and irreversibly inactivated. The functional roles of the cofactors have not been established, but NAD super(+) appears not to be a reactant and there is no evidence for reduction of the nucleotide during substrate cleavage. In solution, native CelF exists as a homotetramer (M sub(w), ~200,000) composed of noncovalently linked subunits, and this oligomeric structure is maintained independently of the presence or absence of a metal ion. The molecular weight of the CelF monomer (M sub(r) ~50,000), estimated by sodium dodecyl sulfate- polyacrylamide gel electrophoresis, is in agreement with that calculated from the amino acid sequence of the polypeptide (450 residues; M sub(r) = 50,512). Comparative sequence alignments provide tentative identification of the NAD super(+)-binding domain (residues 7 to 40) and catalytically important glutamyl residues (Glu super(112) and Glu super(356)) of CelF. JF - Journal of Bacteriology AU - Thompson, J AU - Ruvinov, S B AU - Freedberg, DI AU - Hall, B G AD - National Institutes of Health, Bldg. 30, Room 528, Convent Dr. 4350, Bethesda MD 20892-4350, jthompson@dir.nidcr.nih.gov Y1 - 1999/12// PY - 1999 DA - Dec 1999 SP - 7339 EP - 7345 VL - 181 IS - 23 SN - 0021-9193, 0021-9193 KW - CelF protein KW - celF gene KW - cellobiose-6-phosphate hydrolase KW - cloning KW - glycosyl hydrolase KW - structure-activity relationships KW - Microbiology Abstracts B: Bacteriology KW - Ions KW - Metals KW - Genes KW - Escherichia coli KW - Operons KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17341782?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Cellobiose-6-Phosphate+Hydrolase+%28CelF%29+of+Escherichia+coli%3A+Characterization+and+Assignment+to+the+Unusual+Family+4+of+Glycosylhydrolases&rft.au=Thompson%2C+J%3BRuvinov%2C+S+B%3BFreedberg%2C+DI%3BHall%2C+B+G&rft.aulast=Thompson&rft.aufirst=J&rft.date=1999-12-01&rft.volume=181&rft.issue=23&rft.spage=7339&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Metals; Ions; Genes; Operons ER - TY - JOUR T1 - Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. AN - 69321885; 10579712 AB - The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated. In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD. JF - The Journal of cell biology AU - Sullivan, T AU - Escalante-Alcalde, D AU - Bhatt, H AU - Anver, M AU - Bhat, N AU - Nagashima, K AU - Stewart, C L AU - Burke, B AD - Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1999/11/29/ PY - 1999 DA - 1999 Nov 29 SP - 913 EP - 920 VL - 147 IS - 5 SN - 0021-9525, 0021-9525 KW - Lamins KW - 0 KW - Nuclear Proteins KW - Index Medicus KW - Animals KW - Homozygote KW - Humans KW - Mice KW - Mice, Knockout KW - Mutagenesis, Site-Directed KW - Fibroblasts -- pathology KW - Heterozygote Detection KW - Transfection KW - Mice, Inbred C57BL KW - Gene Targeting KW - Immunohistochemistry KW - Sequence Deletion KW - Nuclear Proteins -- deficiency KW - Nuclear Proteins -- genetics KW - Muscular Dystrophies -- pathology KW - Muscular Dystrophies -- embryology KW - Nuclear Envelope -- pathology KW - Nuclear Envelope -- metabolism KW - Nuclear Proteins -- biosynthesis KW - Muscular Dystrophies -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69321885?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+cell+biology&rft.atitle=Loss+of+A-type+lamin+expression+compromises+nuclear+envelope+integrity+leading+to+muscular+dystrophy.&rft.au=Sullivan%2C+T%3BEscalante-Alcalde%2C+D%3BBhatt%2C+H%3BAnver%2C+M%3BBhat%2C+N%3BNagashima%2C+K%3BStewart%2C+C+L%3BBurke%2C+B&rft.aulast=Sullivan&rft.aufirst=T&rft.date=1999-11-29&rft.volume=147&rft.issue=5&rft.spage=913&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+cell+biology&rft.issn=00219525&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-30 N1 - Date created - 1999-12-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1976 Feb;56(2):245-63 [1255758] J Cell Sci. 1999 Aug;112 ( Pt 15):2571-82 [10393813] Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189-92 [6583703] Nature. 1986 Feb 6-12;319(6053):463-8 [3453101] Cell. 1987 Nov 6;51(3):383-92 [3311384] Annu Rev Cell Biol. 1988;4:335-74 [2461721] Development. 1989 Feb;105(2):365-78 [2680424] J Cell Sci. 1990 Apr;95 ( Pt 4):587-98 [2200797] J Cell Biol. 1990 Dec;111(6 Pt 1):2225-34 [2277058] Eur J Cell Biol. 1992 Apr;57(2):172-83 [1511695] Cell. 1993 Jul 2;73(7):1267-79 [8324822] Methods Enzymol. 1993;225:823-55 [8231889] Nat Genet. 1994 Dec;8(4):323-7 [7894480] Curr Opin Cell Biol. 1995 Feb;7(1):118-25 [7538772] Int Rev Cytol. 1995;162B:141-82 [8557486] Nat Genet. 1996 Mar;12(3):254-9 [8589715] Hum Mol Genet. 1996 Jun;5(6):801-8 [8776595] J Cell Biol. 1997 Mar 24;136(6):1201-12 [9087437] J Cell Biol. 1997 Jun 2;137(5):1001-16 [9166402] J Cell Biol. 1997 Jun 16;137(6):1199-210 [9182656] J Cell Biol. 1997 Sep 22;138(6):1193-206 [9298976] Biol Cell. 1997 May;89(2):85-97 [9351189] Science. 1998 Jan 23;279(5350):514-9 [9438837] Annu Rev Cell Dev Biol. 1997;13:669-95 [9442884] J Biol Chem. 1998 Feb 13;273(7):4213-9 [9461618] J Cell Sci. 1998 Mar;111 ( Pt 6):781-92 [9472006] J Struct Biol. 1998;122(1-2):42-66 [9724605] Nat Genet. 1999 Mar;21(3):285-8 [10080180] Neuromuscul Disord. 1999 Mar;9(2):115-21 [10220867] J Cell Sci. 1999 Jun;112 ( Pt 11):1709-19 [10318763] J Cell Sci. 1999 Jul;112 ( Pt 13):2253-64 [10362555] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5584-8 [146200] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. AN - 69288581; 10572151 AB - Whether the consumption of caffeine during pregnancy increases the risk of spontaneous abortion is controversial. Prior studies have determined caffeine consumption by questionnaire. We used a biologic marker, such as serum paraxanthine, a metabolite of caffeine, to measure the dose of caffeine. In a nested case-control study, we measured serum paraxanthine in 591 women who had spontaneous abortions at less than 140 days' gestation and in 2558 matched women from the same clinic who gave birth to live infants at 28 weeks' gestation or later and who had serum drawn on the same day of gestation as the women who had abortions. The women were enrolled in the Collaborative Perinatal Project during the period from 1959 to 1966, and serum paraxanthine was measured over 30 years later. A total of 487 women who had spontaneous abortions (82 percent) and 2087 controls (82 percent) had quantifiable serum paraxanthine concentrations. However, the mean serum paraxanthine concentration was higher in the women who had spontaneous abortions than in the controls (752 vs. 583 ng per milliliter, P<0.001). The odds ratio for spontaneous abortion was not significantly elevated in the women who had serum paraxanthine concentrations of 1845 ng per milliliter or lower, corresponding to the 95th percentile of the matched women. However, the adjusted odds ratio for spontaneous abortion among women with serum paraxanthine concentrations higher than 1845 ng per milliliter, as compared with women who had concentrations below 50 ng per milliliter, was 1.9 (95 percent confidence interval, 1.2 to 2.8). Only extremely high serum paraxanthine concentrations are associated with spontaneous abortion. This suggests that moderate consumption of caffeine is unlikely to increase the risk of spontaneous abortion. JF - The New England journal of medicine AU - Klebanoff, M A AU - Levine, R J AU - DerSimonian, R AU - Clemens, J D AU - Wilkins, D G AD - Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7510, USA. mk90h@nih.gov Y1 - 1999/11/25/ PY - 1999 DA - 1999 Nov 25 SP - 1639 EP - 1644 VL - 341 IS - 22 SN - 0028-4793, 0028-4793 KW - Caffeine KW - 3G6A5W338E KW - Theophylline KW - C137DTR5RG KW - 1,7-dimethylxanthine KW - Q3565Y41V7 KW - Abridged Index Medicus KW - Index Medicus KW - Odds Ratio KW - Risk Factors KW - Humans KW - Adult KW - Retrospective Studies KW - Case-Control Studies KW - Female KW - Pregnancy KW - Caffeine -- blood KW - Caffeine -- administration & dosage KW - Abortion, Spontaneous -- chemically induced KW - Caffeine -- adverse effects KW - Theophylline -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69288581?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Maternal+serum+paraxanthine%2C+a+caffeine+metabolite%2C+and+the+risk+of+spontaneous+abortion.&rft.au=Klebanoff%2C+M+A%3BLevine%2C+R+J%3BDerSimonian%2C+R%3BClemens%2C+J+D%3BWilkins%2C+D+G&rft.aulast=Klebanoff&rft.aufirst=M&rft.date=1999-11-25&rft.volume=341&rft.issue=22&rft.spage=1639&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-30 N1 - Date created - 1999-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. AN - 69304457; 10570194 AB - An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P-) cells identified a novel gene product that inhibits neoplastic transformation. The JB6 P+ and P- cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P- cells do not. A differentially displayed fragment, A7-1, was preferentially expressed in P- cells at levels >/=10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs, also known as MA-3 or TIS, and analogous to human H731 and 197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P- than in P+ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P- cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (P+) phenotype. The antisense-transfected cells were reverted to their initial P- phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Cmarik, J L AU - Min, H AU - Hegamyer, G AU - Zhan, S AU - Kulesz-Martin, M AU - Yoshinaga, H AU - Matsuhashi, S AU - Colburn, N H AD - Basic Research Laboratory, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD 21702, USA. cmarik@ncifcrf.gov Y1 - 1999/11/23/ PY - 1999 DA - 1999 Nov 23 SP - 14037 EP - 14042 VL - 96 IS - 24 SN - 0027-8424, 0027-8424 KW - Apoptosis Regulatory Proteins KW - 0 KW - PDCD4 protein, human KW - Pdcd4 protein, mouse KW - Proteins KW - RNA, Messenger KW - RNA-Binding Proteins KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Immunoblotting KW - Humans KW - Gene Expression KW - Rabbits KW - Mice KW - Mice, Inbred BALB C KW - Proteins -- genetics KW - Phenotype KW - Tumor Cells, Cultured KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Keratinocytes -- cytology KW - Cell Line KW - Protein Biosynthesis KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69304457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Differentially+expressed+protein+Pdcd4+inhibits+tumor+promoter-induced+neoplastic+transformation.&rft.au=Cmarik%2C+J+L%3BMin%2C+H%3BHegamyer%2C+G%3BZhan%2C+S%3BKulesz-Martin%2C+M%3BYoshinaga%2C+H%3BMatsuhashi%2C+S%3BColburn%2C+N+H&rft.aulast=Cmarik&rft.aufirst=J&rft.date=1999-11-23&rft.volume=96&rft.issue=24&rft.spage=14037&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1996 Feb 1;56(3):483-9 [8564958] Gene. 1995 Dec 12;166(2):297-301 [8543179] EMBO J. 1996 Sep 16;15(18):4852-61 [8890159] Biochem Biophys Res Commun. 1996 Nov 1;228(1):7-13 [8912629] Mol Carcinog. 1997 Jul;19(3):204-12 [9254887] Cancer Res. 1997 Aug 15;57(16):3569-76 [9270030] Pharmacol Ther. 1997;74(3):317-32 [9352587] Carcinogenesis. 1998 Apr;19(4):683-6 [9600355] Oncogene. 1998 May 28;16(21):2711-21 [9652737] Oncogene. 1998 Jul 2;16(26):3387-96 [9692546] Gene. 1998 Jul 30;215(2):453-9 [9714845] J Immunol. 1998 Oct 1;161(7):3493-500 [9759869] Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9827-32 [10449779] Cancer Res. 1978 Mar;38(3):624-34 [626967] Nature. 1979 Oct 18;281(5732):589-91 [492322] Proc Natl Acad Sci U S A. 1981 Nov;78(11):6912-6 [6947266] Carcinogenesis. 1985 Sep;6(9):1245-54 [2411440] Carcinogenesis. 1986 Sep;7(9):1425-9 [3091282] Carcinogenesis. 1988 Jan;9(1):171-4 [2446796] Science. 1989 Feb 17;243(4893):947-50 [2465572] Science. 1989 May 5;244(4904):566-9 [2541502] Science. 1992 Aug 14;257(5072):967-71 [1354393] Mol Carcinog. 1992;6(3):221-9 [1445622] Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2827-31 [8464896] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):609-13 [8290571] Cancer Res. 1994 Mar 1;54(5):1139-44 [8118794] Carcinogenesis. 1994 May;15(5):1001-4 [8200060] Mol Carcinog. 1994 Oct;11(2):115-24 [7916993] Mol Biotechnol. 1996 Aug;6(1):7-15 [8887357] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selection of Keratinocytes Transduced with the Multidrug Resistance Gene in an in Vitro Skin Model Presents a Strategy for Enhancing Gene Expression in Vivo AN - 17429676; 4645693 AB - In gene therapy studies, achieving prolonged, high-level gene expression in a significant percentage of cells has been difficult. One solution to enhance expression would be to select for cells expressing both the desired gene and a linked selectable marker gene in a bicistronic vector. As a potential target tissue, the skin is easily accessible for safe topical application of a selecting agent that could lead to significant gene expression in a high percentage of keratinocytes. To test the feasibility of such an approach, a skin raft culture model was developed. Human keratinocytes were transduced with the multidrug resistance (MDR) gene, which confers resistance to a variety of cytostatic and antimitotic compounds, such as colchicine. While growing on acellular dermis, transduced keratinocytes were treated with various doses of colchicine (10-50 ng/ml). Colchicine treatment increased the percentage of keratinocytes expressing MDR to almost 100% in raft cultures, Significantly, keratinocytes in colchicine-treated, MDR-transduced raft cultures were able to proliferate normally and form a stratified, differentiated epidermis. This model suggests that topical selection for MDR-expressing keratinocytes in vivo should be feasible without hampering the biologic integrity of skin. Thus, topical selection leading to enhanced expression of a desired gene, linked to a resistance gene, holds future promise for skin gene therapy. JF - Human Gene Therapy AU - Pfuetzner, W AU - Hengge, U R AU - Joari, MA AU - Foster, R-A AU - Vogel, J C AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 12N238, 9000 Rockville Pike, Bethesda, MD 20892-1908, Jonvogel@Box-j.nih.gov Y1 - 1999/11/20/ PY - 1999 DA - 1999 Nov 20 SP - 2811 EP - 2821 VL - 10 IS - 17 SN - 1043-0342, 1043-0342 KW - man KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Skin KW - Gene therapy KW - Cloning vectors KW - Multidrug resistance KW - Keratinocytes KW - Transduction KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17429676?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Selection+of+Keratinocytes+Transduced+with+the+Multidrug+Resistance+Gene+in+an+in+Vitro+Skin+Model+Presents+a+Strategy+for+Enhancing+Gene+Expression+in+Vivo&rft.au=Pfuetzner%2C+W%3BHengge%2C+U+R%3BJoari%2C+MA%3BFoster%2C+R-A%3BVogel%2C+J+C&rft.aulast=Pfuetzner&rft.aufirst=W&rft.date=1999-11-20&rft.volume=10&rft.issue=17&rft.spage=2811&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950016546 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Keratinocytes; Multidrug resistance; Transduction; Skin; Gene therapy; Cloning vectors DO - http://dx.doi.org/10.1089/10430349950016546 ER - TY - JOUR T1 - Polarized Secretion of Transgene Products from Salivary Glands in Vivo AN - 17429593; 4645691 AB - Previously we have shown that salivary glands are able to secrete a transgene-encoded protein into serum as well as saliva. This result and other published data suggest that salivary glands may be a useful target site for vectors encoding therapeutic proteins for systemic delivery. The aim of the present study was to assess in vivo if transgene-encoded secretory proteins follow distinct, polarized sorting pathways as has been shown to occur "classically" in cell biological studies in vitro. Four first-generation, E1 super(-), type 5 recombinant adenoviruses were used to deliver different transgenes to a rat submandibular cell line in vitro or to rat submandibular glands in vivo. Subsequently, the secretory distribution of the encoded proteins was determined. Luciferase, which has no signal peptide, served as a cell-associated, negative control and was used to correct for any nonspecific secretory protein release from cells. The three remaining transgene products tested, human tissue kallikrein (hK1), human growth hormone (hGH), and human alpha sub(1)-antitrypsin (h alpha 1AT), were predominantly secreted (>96%) in vitro. Most importantly, in vivo, after a parasympathomimetic secretory stimulus, both hK1 and hGH were secreted primarily in an exocrine manner into saliva. Conversely, h alpha 1AT was predominantly secreted into the bloodstream, i.e., in an endocrine manner. The aggregate results are consistent with the recognition of signals encoded within the transgenes that result in specific patterns of polarized protein secretion from rat submandibular gland cells in vivo. JF - Human Gene Therapy AU - Baum, B J AU - Berkman, ME AU - Marmary, Y AU - Goldsmith, C M AU - Baccaglini, L AU - Wang, S AU - Wellner, R B AU - Hoque, ATMS AU - Atkinson, J C AU - Yamagishi, H AU - Kagami, H AU - Parlow, A F AU - Chao, J AD - GTTB, NIDCR, NIH, Bldg. 10, Rm. 1N113, MSC-1190, Bethesda, MD 20892, bruce_j_baum@nih.gov Y1 - 1999/11/20/ PY - 1999 DA - 1999 Nov 20 SP - 2789 EP - 2797 VL - 10 IS - 17 SN - 1043-0342, 1043-0342 KW - rats KW - Adenovirus KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene transfer KW - Submandibular gland KW - Salivary gland KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17429593?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Polarized+Secretion+of+Transgene+Products+from+Salivary+Glands+in+Vivo&rft.au=Baum%2C+B+J%3BBerkman%2C+ME%3BMarmary%2C+Y%3BGoldsmith%2C+C+M%3BBaccaglini%2C+L%3BWang%2C+S%3BWellner%2C+R+B%3BHoque%2C+ATMS%3BAtkinson%2C+J+C%3BYamagishi%2C+H%3BKagami%2C+H%3BParlow%2C+A+F%3BChao%2C+J&rft.aulast=Baum&rft.aufirst=B&rft.date=1999-11-20&rft.volume=10&rft.issue=17&rft.spage=2789&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950016528 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adenovirus; Gene transfer; Salivary gland; Submandibular gland DO - http://dx.doi.org/10.1089/10430349950016528 ER - TY - JOUR T1 - A Sp1 binding site of the tumor necrosis factor alpha promoter functions as a nitric oxide response element. AN - 69284746; 10559188 AB - Regulation of gene transcription is an incompletely understood function of nitric oxide (NO). Human leukocytes produce increased amounts of tumor necrosis factor alpha (TNF-alpha) in response to NO. This effect is associated with decreases in intracellular cAMP, suggesting that NO might regulate gene transcription through promoter sequences sensitive to cAMP such as cAMP response elements (CRE) and Sp1 binding sites. Here we report that a Sp1 binding site in the TNF-alpha promoter conveys NO responsiveness. Human U937 cells were differentiated for TNF-alpha production with phorbol 12-myristate 13-acetate. NO donors and H89, an inhibitor of cAMP-dependent protein kinase increased, while dibutyryl cAMP (Bt(2)cAMP) decreased TNF-alpha promoter activity. Deletion or mutation of the proximal Sp1 site, but not the CRE site, abolished the activating effects of NO donors and H89. Further, NO- and H89-mediated increases in TNF-alpha promoter activity were associated with decreased Sp1 binding. The insertion of Sp1 sites into a minimal cytomegalovirus promoter conferred NO responsiveness, an effect blocked by Bt(2)cAMP. Mutation of these inserted Sp1 sites prevented this heterologous promoter from responding to NO, H89 and Bt(2)cAMP. These results identify the Sp1 binding site as a promoter motif that allows NO to control gene transcription. JF - The Journal of biological chemistry AU - Wang, S AU - Wang, W AU - Wesley, R A AU - Danner, R L AD - Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/11/19/ PY - 1999 DA - 1999 Nov 19 SP - 33190 EP - 33193 VL - 274 IS - 47 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Sp1 Transcription Factor KW - Tumor Necrosis Factor-alpha KW - Nitric Oxide KW - 31C4KY9ESH KW - DNA KW - 9007-49-2 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Base Sequence KW - Enzyme Activation KW - Humans KW - DNA -- metabolism KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Protein Binding KW - U937 Cells KW - Binding Sites KW - Sp1 Transcription Factor -- genetics KW - Promoter Regions, Genetic KW - Sp1 Transcription Factor -- metabolism KW - Nitric Oxide -- metabolism KW - Tumor Necrosis Factor-alpha -- physiology KW - Nitric Oxide -- physiology KW - Tumor Necrosis Factor-alpha -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69284746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=A+Sp1+binding+site+of+the+tumor+necrosis+factor+alpha+promoter+functions+as+a+nitric+oxide+response+element.&rft.au=Wang%2C+S%3BWang%2C+W%3BWesley%2C+R+A%3BDanner%2C+R+L&rft.aulast=Wang&rft.aufirst=S&rft.date=1999-11-19&rft.volume=80&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mechanism of organic anion transport across the apical membrane of choroid plexus. AN - 69283649; 10559217 AB - The mechanism and membrane localization of choroid plexus (CP) organic anion transport were determined in apical (or brush border) membrane vesicles isolated from bovine choroid plexus and in intact CP tissue from cow and rat. Brush border membrane vesicles were enriched in Na(+),K(+)-ATPase (20-fold; an apical marker in CP) and demonstrated specific, sodium-coupled transport of proline, glucose, and glutarate. Vesicular uptake of the anionic herbicide 2, 4-dichlorophenoxyacetic acid (2,4-D) was markedly stimulated by an inward sodium gradient but only in the presence of glutarate, indicating the presence of apical dicarboxylate/organic anion exchange. Consistent with this interpretation, an imposed outward glutarate gradient stimulated 2,4-D uptake in the absence of sodium. Under both conditions, uptake was dramatically slowed and overshoot was abolished by probenecid. Likewise, apical accumulation of 2,4-D by intact bovine choroid plexus tissue in vitro was stimulated by external glutarate in the presence of sodium. Glutarate stimulation was abolished by 5 mM LiCl. Identical findings were obtained using rat CP tissue, which showed both sodium/glutarate-stimulated 2,4-D (tissue/medium (T/M) approximately 8) and p-aminohippurate (T/M = 2) transport. Finally, since the renal exchanger (rROAT1) has been cloned in rat kidney, a rROAT1-green fluorescent protein construct was used to analyze exchanger distribution directly in transiently transfected rat CP. As predicted by the functional studies, the fluorescently tagged transporter was seen in apical but not basolateral membranes of the CP. JF - The Journal of biological chemistry AU - Pritchard, J B AU - Sweet, D H AU - Miller, D S AU - Walden, R AD - Laboratory of Pharmacology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. pritchard@niehs.nih.gov Y1 - 1999/11/19/ PY - 1999 DA - 1999 Nov 19 SP - 33382 EP - 33387 VL - 274 IS - 47 SN - 0021-9258, 0021-9258 KW - Anion Transport Proteins KW - 0 KW - Anions KW - Carrier Proteins KW - Glutarates KW - Herbicides KW - Luminescent Proteins KW - Recombinant Fusion Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - 2,4-Dichlorophenoxyacetic Acid KW - 2577AQ9262 KW - Proline KW - 9DLQ4CIU6V KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Animals KW - Herbicides -- metabolism KW - Carrier Proteins -- metabolism KW - Microvilli -- metabolism KW - Luminescent Proteins -- metabolism KW - Ion Transport KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Rats, Sprague-Dawley KW - Cattle KW - 2,4-Dichlorophenoxyacetic Acid -- metabolism KW - Male KW - Proline -- metabolism KW - Glutarates -- metabolism KW - Choroid Plexus -- metabolism KW - Glucose -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69283649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Drinking+water+disinfection+byproducts%3A+review+and+approach+to+toxicity+evaluation.&rft.au=Boorman%2C+G+A&rft.aulast=Boorman&rft.aufirst=G&rft.date=1999-02-01&rft.volume=107+Suppl+1&rft.issue=&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility. AN - 69284104; 10564681 AB - The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. Our study included 466 women with incident cases of breast cancer occurring from May 1989 through May 1994 and 466 matched control subjects. These individuals were part of a prospective cohort of U.S. women (i.e., the Nurses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression models were used to estimate the association between genetic polymorphisms and breast cancer risk. The GSTM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0. 86 [95% CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decreased risk of breast cancer associated with the GSTT1 null genotype was observed among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was not substantially modified by cigarette smoking. Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions. JF - Journal of the National Cancer Institute AU - García-Closas, M AU - Kelsey, K T AU - Hankinson, S E AU - Spiegelman, D AU - Springer, K AU - Willett, W C AU - Speizer, F E AU - Hunter, D J AD - M. García-Closas, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Y1 - 1999/11/17/ PY - 1999 DA - 1999 Nov 17 SP - 1960 EP - 1964 VL - 91 IS - 22 SN - 0027-8874, 0027-8874 KW - DNA Primers KW - 0 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - United States KW - Polymerase Chain Reaction KW - Odds Ratio KW - Prospective Studies KW - Disease Susceptibility KW - Logistic Models KW - Humans KW - Nurses KW - Case-Control Studies KW - Female KW - Breast Neoplasms -- genetics KW - Polymorphism, Genetic KW - Glutathione Transferase -- genetics KW - Breast Neoplasms -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69284104?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Glutathione+S-transferase+mu+and+theta+polymorphisms+and+breast+cancer+susceptibility.&rft.au=Garc%C3%ADa-Closas%2C+M%3BKelsey%2C+K+T%3BHankinson%2C+S+E%3BSpiegelman%2C+D%3BSpringer%2C+K%3BWillett%2C+W+C%3BSpeizer%2C+F+E%3BHunter%2C+D+J&rft.aulast=Garc%C3%ADa-Closas&rft.aufirst=M&rft.date=1999-11-17&rft.volume=91&rft.issue=22&rft.spage=1960&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-03 N1 - Date created - 1999-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The flattened face of type II beta phosphatidylinositol phosphate kinase binds acidic phospholipid membranes. AN - 69274422; 10563796 AB - Type II beta phosphatidylinositol phosphate kinase is a representative phosphatidylinositol phosphate kinase that is active against membrane-bound substrates. The structure of the enzyme contains a flattened basic face that spans the crystallographic dimer interface and is adjacent to the active site. Analytical ultracentrifugation shows that phosphatidylinositol phosphate kinase is a dimer in solution. Modeling suggested that the flattened face binds to acidic phospholipids by electrostatic interactions. The enzyme binds to acidic vesicles containing phosphatidylserine, phosphatidic acid, or phosphoinositides mixed with phosphatidylcholine, but not to neutral phosphatidylcholine vesicles. Binding to acidic vesicles is abolished in the presence of 1.0 M NaCl, consistent with an essential electrostatic contribution to the free energy of binding. The +14 charge on the flattened face of the dimer was reduced to +2 in the triple mutant Lys72Glu/Lys76Glu/Lys78Glu. The mutation has no effect on dimerization, but reduces the apparent KA for 25% phosphatidylserine/75% phosphatidylcholine mixed vesicles by 16-fold. The reduction in the level of binding can be ascribed to a loss of electrostatic interactions based on the finite difference solution to the Poisson-Boltzmann equation. The mutant reduces catalytic activity toward phosphatidylinositol 5-phosphate by approximately 50-fold. The wild-type enzyme binds half-maximally to phosphatidylinositol 4,5-bisphosphate-containing vesicles at a mole fraction of 0.3% in a phosphatidylcholine background, as compared to a 22% mole fraction in phosphatidylserine. The binding to phosphatidylinositol 4,5-bisphosphate-containing membranes is less sensitive to salt and to the triple mutation than binding to phosphatidylserine-containing membranes, suggesting that at least part of phosphatidylinositol 4,5-bisphosphate's interaction with the enzyme is independent of the flattened face. It is concluded that the flattened face of type II beta phosphatidylinositol phosphate kinase binds to membranes through nonspecific interactions, and that this interaction is essential for efficient catalysis. JF - Biochemistry AU - Burden, L M AU - Rao, V D AU - Murray, D AU - Ghirlando, R AU - Doughman, S D AU - Anderson, R A AU - Hurley, J H AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-0580, USA. Y1 - 1999/11/16/ PY - 1999 DA - 1999 Nov 16 SP - 15141 EP - 15149 VL - 38 IS - 46 SN - 0006-2960, 0006-2960 KW - Lipid Bilayers KW - 0 KW - Phospholipids KW - Recombinant Fusion Proteins KW - Glutamic Acid KW - 3KX376GY7L KW - 1-Phosphatidylinositol 4-Kinase KW - EC 2.7.1.67 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Models, Molecular KW - Humans KW - Hydrogen-Ion Concentration KW - Lysine -- genetics KW - Ultracentrifugation KW - Enzyme Activation -- genetics KW - Glutamic Acid -- genetics KW - Static Electricity KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Recombinant Fusion Proteins -- genetics KW - Models, Chemical KW - Protein Binding -- genetics KW - Binding Sites -- genetics KW - Recombinant Fusion Proteins -- chemical synthesis KW - 1-Phosphatidylinositol 4-Kinase -- chemistry KW - 1-Phosphatidylinositol 4-Kinase -- metabolism KW - Phospholipids -- chemistry KW - Phospholipids -- metabolism KW - Lipid Bilayers -- chemistry KW - Lipid Bilayers -- metabolism KW - 1-Phosphatidylinositol 4-Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69274422?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+personality+and+social+psychology&rft.atitle=The+effects+of+involvement+on+response+to+argument+quantity+and+quality%3A+central+and+peripheral+routes+to+persuasion&rft.au=Petty%2C+R+E&rft.aulast=Petty&rft.aufirst=R&rft.date=1984-01-01&rft.volume=46&rft.issue=1&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Journal+of+personality+and+social+psychology&rft.issn=00223514&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-20 N1 - Date created - 1999-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of dietary iron overload on fumonisin B1-induced cancer promotion in the rat liver. AN - 69420092; 10656628 AB - The present study was performed to determine whether excess hepatic iron modulates the cancer-initiating and promoting properties of FB1. Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) control diet (AIN, n = 8); (ii) FB1 250 mg/kg diet (FB1, n = 10); (iii) 1-2% carbonyl iron (CI, n = 10); or (iv) FB1 plus iron loading (FB1/CI, n = 10) for 5 weeks (2 x 2 factorial design). Hepatic iron concentrations in iron-loaded animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 micromol/g dry weight (FB1/CI) (mean +/- SEM). All the FB1-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine transaminase (ALT) levels. FB1 appeared to augment iron-induced hepatic lipid peroxidation, as measured by the generation of thiobarbituric acid reacting substances (TBARS) in liver homogenates (P < 0.0001). Morphometric analysis showed that FB1 caused a significantly greater mean +/- SEM number of 'enzyme-altered' foci and nodules per cm2 (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (%) of liver occupied by foci and nodules (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB1/CI. The addition of FB1 to dietary iron loading caused a shift in distribution of iron from hepatocytes to Kupffer cells, probably due to phagocytosis of necrotic iron-loaded hepatocytes. In conclusion, (i) FB1 appears to cause toxicity in the liver independently from effects on lipid peroxidation; (ii) FB1 has a potentiating effect on iron-induced lipid peroxidation; and (iii) dietary iron loading appears to protect against the cancer promoting properties of FB1, possibly due to a stimulatory effect of iron on hepatocyte regeneration. JF - Cancer letters AU - Lemmer, E R AU - Gelderblom, W C AU - Shephard, E G AU - Abel, S AU - Seymour, B L AU - Cruse, J P AU - Kirsch, R E AU - Marasas, W F AU - Hall, P M AD - MRC/UCT Liver Research Centre, University of Cape Town, South Africa. eric_lemmer@nih.gov Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 207 EP - 215 VL - 146 IS - 2 SN - 0304-3835, 0304-3835 KW - Carboxylic Acids KW - 0 KW - Carcinogens, Environmental KW - Fumonisins KW - Isoenzymes KW - fumonisin B1 KW - 3ZZM97XZ32 KW - Glutathione S-Transferase pi KW - EC 2.5.1.18 KW - Glutathione Transferase KW - Gstp1 protein, rat KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Liver -- pathology KW - Glutathione Transferase -- metabolism KW - Liver -- metabolism KW - Weight Gain KW - Organ Size KW - Lipid Peroxidation KW - Male KW - Isoenzymes -- metabolism KW - Liver Neoplasms, Experimental -- pathology KW - Iron Overload -- physiopathology KW - Liver Neoplasms, Experimental -- chemically induced KW - Carcinogens, Environmental -- toxicity KW - Liver Neoplasms, Experimental -- prevention & control KW - Carboxylic Acids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69420092?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=The+effects+of+dietary+iron+overload+on+fumonisin+B1-induced+cancer+promotion+in+the+rat+liver.&rft.au=Lemmer%2C+E+R%3BGelderblom%2C+W+C%3BShephard%2C+E+G%3BAbel%2C+S%3BSeymour%2C+B+L%3BCruse%2C+J+P%3BKirsch%2C+R+E%3BMarasas%2C+W+F%3BHall%2C+P+M&rft.aulast=Lemmer&rft.aufirst=E&rft.date=1999-11-15&rft.volume=146&rft.issue=2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-17 N1 - Date created - 2000-02-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer. AN - 69337293; 10585768 AB - We have previously identified a chromosomal rearrangement between fibroblast growth factor receptor 2 (FGFR2) and a novel gene, FRAG1, in a rodent model of osteosarcoma. To assess the potential role of FRAG1 in disease further, we have isolated cDNA and genomic clones of human FRAG1. Sequence analysis of the cDNA revealed the presence of an insertion not contained in the original FRAG1 sequence. This insertion in human FRAG1 encoded a region highly homologous to and immediately following the first 55 amino acids of the protein, indicating the presence of a repetitive domain within FRAG1, designated the FRAG1 homology (FH) domain. Analysis of FRAG1 gene structure revealed that the FH domains were encoded by tandem duplicated exons. Database searches identified several transmembrane proteins displaying homology to the FH domain of FRAG1. In addition, hydropathy analysis predicted FRAG1 to encode an integral membrane protein with multiple membrane-spanning segments. FRAG1 mRNA was ubiquitously expressed in human adult tissues and several tumor cell lines at varying levels of abundance. Human FRAG1 was mapped by fluorescence in situ hybridization and radiation hybrid analysis to chromosome 11 at band p15.5, a region implicated in Beckwith-Wiedemann syndrome and a region of frequent loss of heterozygosity in multiple tumor types. These results suggest that FRAG1 may be a useful candidate gene for genetic disorders associated with alterations at 11p15.5. Copyright 1999 Academic Press. JF - Genomics AU - Lorenzi, M V AU - Castagnino, P AU - Aaronson, D C AU - Lieb, D C AU - Lee, C C AU - Keck, C L AU - Popescu, N C AU - Miki, T AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Matthew.Lorenzi@phwilm.zeneca.com Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 59 EP - 66 VL - 62 IS - 1 SN - 0888-7543, 0888-7543 KW - DNA, Complementary KW - 0 KW - FRAG1 protein, human KW - Nuclear Proteins KW - RNA, Messenger KW - Index Medicus KW - Gene Duplication KW - DNA, Complementary -- genetics KW - Humans KW - In Situ Hybridization, Fluorescence KW - Organ Specificity KW - Amino Acid Sequence KW - RNA, Messenger -- biosynthesis KW - Exons -- genetics KW - Base Sequence KW - Tumor Cells, Cultured KW - Sequence Alignment KW - Beckwith-Wiedemann Syndrome -- genetics KW - Adult KW - Chromosome Aberrations KW - Molecular Sequence Data KW - Consensus Sequence KW - Sequence Homology, Amino Acid KW - Repetitive Sequences, Nucleic Acid KW - Mutagenesis, Insertional KW - Nuclear Proteins -- genetics KW - Loss of Heterozygosity KW - Genes KW - Chromosomes, Human, Pair 11 -- genetics KW - Nuclear Proteins -- biosynthesis KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69337293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Human+FRAG1+encodes+a+novel+membrane-spanning+protein+that+localizes+to+chromosome+11p15.5%2C+a+region+of+frequent+loss+of+heterozygosity+in+cancer.&rft.au=Lorenzi%2C+M+V%3BCastagnino%2C+P%3BAaronson%2C+D+C%3BLieb%2C+D+C%3BLee%2C+C+C%3BKeck%2C+C+L%3BPopescu%2C+N+C%3BMiki%2C+T&rft.aulast=Lorenzi&rft.aufirst=M&rft.date=1999-11-15&rft.volume=62&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-04 N1 - Date created - 2000-02-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF159620; GENBANK; AF159621; AF159615; AF159616; AF159617; AF159618; AF159619 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of KAI1 expression in the progression of colorectal cancer. AN - 69323746; 10582691 AB - The transmembrane 4 superfamily member KAI1 (CD82) has been shown to inhibit pulmonary metastases in experimental metastasis models of prostate cancer and melanoma. KAI1 expression is decreased in the progression of common solid epithelial tumors of adulthood, including lung, prostate, breast, esophageal, gastric, pancreatic, and bladder cancers. The purpose of our study was to investigate KAI1 expression in the progression of human colorectal cancer. We first analyzed 20 colorectal cancer cell lines by immunoblot techniques. KAI1 was expressed heterogeneously, with the tumor cell lines having a more complex degree of glycosylation compared with that of the normal colonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer cell line but was down-regulated 15-fold in the matched metastatic SW620 cell line. We also investigated KAI1 protein expression by immunohistochemistry in tissues from 84 patients with colorectal cancer. Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3). In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic mucosa (KMS 226) but was expressed at lower levels in the primary tumors (KMS 65; P < 0.0001). In a subset of 12 patients with stage IV metastatic disease, we observed a progressive down-regulation of KAI1, from the normal adjacent colonic mucosa (KMS 193) to the primary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compared with metastasis, P = 0.0135). We found no correlation between loss of KAI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KMS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three comparisons). We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cancer. JF - Cancer research AU - Lombardi, D P AU - Geradts, J AU - Foley, J F AU - Chiao, C AU - Lamb, P W AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 5724 EP - 5731 VL - 59 IS - 22 SN - 0008-5472, 0008-5472 KW - Antigens, CD KW - 0 KW - Antigens, CD82 KW - CD82 protein, human KW - Membrane Glycoproteins KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Index Medicus KW - Liver Neoplasms -- metabolism KW - Analysis of Variance KW - DNA Repair KW - Neoplasm Staging KW - Humans KW - Disease Progression KW - Aged KW - Liver Neoplasms -- secondary KW - Molecular Weight KW - Genotype KW - Adenoma -- metabolism KW - Tumor Cells, Cultured KW - Down-Regulation KW - Adult KW - Genes, p53 -- genetics KW - Middle Aged KW - Carcinoma -- metabolism KW - Male KW - Female KW - Cell Adhesion KW - Membrane Glycoproteins -- chemistry KW - Colonic Neoplasms -- genetics KW - Rectal Neoplasms -- pathology KW - Neoplasm Proteins -- chemistry KW - Rectal Neoplasms -- metabolism KW - Rectal Neoplasms -- genetics KW - Antigens, CD -- chemistry KW - Colon -- metabolism KW - Antigens, CD -- metabolism KW - Colonic Neoplasms -- metabolism KW - Colonic Neoplasms -- pathology KW - Neoplasm Proteins -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69323746?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Loss+of+KAI1+expression+in+the+progression+of+colorectal+cancer.&rft.au=Lombardi%2C+D+P%3BGeradts%2C+J%3BFoley%2C+J+F%3BChiao%2C+C%3BLamb%2C+P+W%3BBarrett%2C+J+C&rft.aulast=Lombardi&rft.aufirst=D&rft.date=1999-11-15&rft.volume=59&rft.issue=22&rft.spage=5724&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphoinositide 3-hydroxide kinase blockade enhances apoptosis in the Ewing's sarcoma family of tumors. AN - 69322549; 10582694 AB - Ewing's sarcoma family of tumors (ESFTs) affects patients between the ages of 3 and 40 years, with most cases occurring in the second decade of life. These tumors contain a characteristic translocation, t(11;22), that produces a unique fusion protein, EWS/FLI-1. EWS/FLI-1 transforms mouse fibroblasts; this transformation requires intact EWS and FLI-1 domains as well as the insulin-like growth factor-I receptor (IGF-IR). The IGF-IR is a well-described transmembrane tyrosine kinase receptor that modulates transformation, cell growth, and survival. IGF-IR survival signaling is mediated through the downstream activation of phosphoinositide 3-OH kinase (PI 3-K) and Akt. Apoptosis, programmed cell death, progresses from a central death signal to a caspase cascade, including activation of caspase-3. Because the IGF-IR has been shown to play a role in the transformation and growth of ESFTs, we wanted to determine the role of downstream molecules in the cellular response to doxorubicin treatment. Doxorubicin increased caspase-3 activity in two ESFT cell lines, TC-32 and TC-71. Concomitant treatment of the doxorubicin-treated cells with IGF-I reduced caspase-3 activity 8-fold in TC-32 and 4-fold in TC-71. To determine whether PI 3-K has a role in IGF-I-mediated survival in ESFTs, PI 3-K was then inhibited with wortmannin and LY294002. Doxorubicin treatment reduced cell number and enhanced apoptosis in PI 3-K inhibited cells compared with noninhibited cells. Akt, a serine/threonine kinase activated downstream of PI 3-K, was investigated to determine whether its constitutive activation would render ESFT cells more resistant to doxorubicin. A constitutively activated Akt was stably transfected into ESFT and those cells with high levels of expression demonstrated increased resistance to doxorubicin-induced caspase-3 activation. These results indicate that ESFT cell lines use an IGF-IR initiated signaling pathway through PI 3-K and Akt for survival when treated with doxorubicin. JF - Cancer research AU - Toretsky, J A AU - Thakar, M AU - Eskenazi, A E AU - Frantz, C N AD - Department of Pediatrics, University of Maryland, Baltimore 21201, USA. jt@helix.nih.gov Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 5745 EP - 5750 VL - 59 IS - 22 SN - 0008-5472, 0008-5472 KW - Androstadienes KW - 0 KW - Antineoplastic Agents KW - Enzyme Inhibitors KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Doxorubicin KW - 80168379AG KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - CASP3 protein, human KW - EC 3.4.22.- KW - Casp3 protein, mouse KW - Caspase 3 KW - Caspases KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Doxorubicin -- antagonists & inhibitors KW - Humans KW - Androstadienes -- pharmacology KW - Insulin-Like Growth Factor I -- pharmacology KW - In Situ Nick-End Labeling KW - Doxorubicin -- pharmacology KW - Cell Transformation, Neoplastic -- chemically induced KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - DNA Fragmentation KW - Protein-Serine-Threonine Kinases -- physiology KW - Antineoplastic Agents -- antagonists & inhibitors KW - Apoptosis -- genetics KW - Sarcoma, Ewing -- physiopathology KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Neoplasm Proteins -- antagonists & inhibitors KW - Sarcoma, Ewing -- enzymology KW - Neoplasm Proteins -- metabolism KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69322549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Induction+of+Protective+Host+Immunity+to+Carcinoembryonic+Antigen+%28CEA%29%2C+a+Self-Antigen+in+CEA+Transgenic+Mice%2C+by+Immunizing+with+a+Recombinant+Vaccinia-CEA+Virus&rft.au=Kass%2C+E%3BSchlom%2C+J%3BThompson%2C+J%3BGuadagni%2C+F%3BGraziano%2C+P%3BGreiner%2C+J+W&rft.aulast=Kass&rft.aufirst=E&rft.date=1999-02-01&rft.volume=59&rft.issue=3&rft.spage=676&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity. AN - 69279568; 10559418 AB - Methamphetamine neurotoxicity has been demonstrated in rodents and nonhuman primates. These neurotoxic effects may be associated with mechanisms involved in oxidative stress and the activation of immediate early genes (IEG). It is not clear, however, whether these IEG responses are involved in a methamphetamine-induced toxic cascade or in protective mechanisms against the deleterious effects of the drug. As a first step toward clarifying this issue further, the present study was thus undertaken to assess the toxic effects of methamphetamine in heterozygous and homozygous c-fos knock-out as well as wild-type mice. Administration of methamphetamine caused significant reduction in [(125)I]RTI-121-labeled dopamine uptake sites, dopamine transporter protein, and tyrosine hydroxylase-like immunohistochemistry in the striata of wild-type mice. These decreases were significantly exacerbated in heterozygous and homozygous c-fos knock-out mice, with the homozygous showing greater loss of striatal dopaminergic markers. Moreover, in comparison with wild-type animals, both genotypes of c-fos knock-out mice showed more DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled nondopaminergic cells in their cortices and striata. In contrast, wild-type mice treated with methamphetamine demonstrated a greater number of glial fibrillary acidic protein-positive cells than did c-fos knock-out mice. These data suggest that c-fos induction in response to toxic doses of methamphetamine might be involved in protective mechanisms against this drug-induced neurotoxicity. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Deng, X AU - Ladenheim, B AU - Tsao, L I AU - Cadet, J L AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224, USA. Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 10107 EP - 10115 VL - 19 IS - 22 KW - Glial Fibrillary Acidic Protein KW - 0 KW - Iodine Radioisotopes KW - Neurotoxins KW - Proto-Oncogene Proteins c-fos KW - Methamphetamine KW - 44RAL3456C KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Corpus Striatum -- cytology KW - Frontal Lobe -- cytology KW - Homozygote KW - Body Temperature -- drug effects KW - Frontal Lobe -- drug effects KW - Dopamine -- metabolism KW - Mice KW - Mice, Knockout KW - Corpus Striatum -- physiology KW - Frontal Lobe -- physiology KW - Heterozygote KW - Corpus Striatum -- drug effects KW - Glial Fibrillary Acidic Protein -- analysis KW - DNA Fragmentation KW - Cerebral Cortex -- cytology KW - Cerebral Cortex -- physiology KW - Cerebral Cortex -- drug effects KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Proto-Oncogene Proteins c-fos -- genetics KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Genes, fos KW - Proto-Oncogene Proteins c-fos -- deficiency KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69279568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Null+mutation+of+c-fos+causes+exacerbation+of+methamphetamine-induced+neurotoxicity.&rft.au=Deng%2C+X%3BLadenheim%2C+B%3BTsao%2C+L+I%3BCadet%2C+J+L&rft.aulast=Deng&rft.aufirst=X&rft.date=1999-11-15&rft.volume=19&rft.issue=22&rft.spage=10107&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-02 N1 - Date created - 1999-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of the invariant chain by protein kinase C regulates MHC class II trafficking to antigen-processing compartments. AN - 69263172; 10553069 AB - The invariant chain (Ii) plays a critical role in the transport of newly synthesized class II molecules to endosomal Ag-processing compartments. Of the two major isoforms of human Ii, only Ii-p35 is phosphorylated in vivo, and inhibiting Ii phosphorylation inhibits the trafficking of newly synthesized class II molecules to Ag-processing compartments. We now report that a member of the protein kinase C family of serine/threonine kinases is responsible for the constitutive phosphorylation of 50% of the total cellular pool of Ii-p35 in a wide variety of APCs, including B lymphocytes, PBMC, immature dendritic cells, and mature dendritic cells. Stimulation of protein kinase C activity in APCs significantly enhanced the kinetics of degradation of class II-associated Ii in Ag-processing compartments and the binding of antigenic peptides to these class II molecules. In cells expressing an Ii-phosphorylation mutant, trafficking of class II molecules to endosomes was impaired and Ii proteolysis was inhibited, demonstrating a direct effect of Ii phosphorylation on MHC class II trafficking. These results demonstrate that phosphorylation of Ii in APCs alters the kinetics of trafficking of newly synthesized class II molecules to lysosomal Ag-processing compartments. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Anderson, H A AU - Bergstralh, D T AU - Kawamura, T AU - Blauvelt, A AU - Roche, P A AD - Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 5435 EP - 5443 VL - 163 IS - 10 SN - 0022-1767, 0022-1767 KW - Antigens, Differentiation, B-Lymphocyte KW - 0 KW - Histocompatibility Antigens Class II KW - Recombinant Fusion Proteins KW - invariant chain KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Abridged Index Medicus KW - Index Medicus KW - Endoplasmic Reticulum -- metabolism KW - HeLa Cells -- metabolism KW - Dendritic Cells -- immunology KW - HeLa Cells -- enzymology KW - Humans KW - Glutathione Transferase -- metabolism KW - HeLa Cells -- immunology KW - Glutathione Transferase -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Phosphorylation KW - Dendritic Cells -- metabolism KW - Biological Transport -- immunology KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Endoplasmic Reticulum -- immunology KW - Protein Kinase C -- metabolism KW - Antigens, Differentiation, B-Lymphocyte -- metabolism KW - Histocompatibility Antigens Class II -- biosynthesis KW - Antigens, Differentiation, B-Lymphocyte -- genetics KW - Histocompatibility Antigens Class II -- genetics KW - Histocompatibility Antigens Class II -- metabolism KW - Antigens, Differentiation, B-Lymphocyte -- biosynthesis KW - Cell Compartmentation -- immunology KW - Antigen Presentation -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69263172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Phosphorylation+of+the+invariant+chain+by+protein+kinase+C+regulates+MHC+class+II+trafficking+to+antigen-processing+compartments.&rft.au=Anderson%2C+H+A%3BBergstralh%2C+D+T%3BKawamura%2C+T%3BBlauvelt%2C+A%3BRoche%2C+P+A&rft.aulast=Anderson&rft.aufirst=H&rft.date=1999-11-15&rft.volume=163&rft.issue=10&rft.spage=5435&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-02 N1 - Date created - 1999-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Responses in refractory hairy cell leukemia to a recombinant immunotoxin. AN - 69262559; 10552943 AB - We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2. The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle. One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25(+) HCL. JF - Blood AU - Kreitman, R J AU - Wilson, W H AU - Robbins, D AU - Margulies, I AU - Stetler-Stevenson, M AU - Waldmann, T A AU - Pastan, I AD - Laboratory of Molecular Biology, the Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 3340 EP - 3348 VL - 94 IS - 10 SN - 0006-4971, 0006-4971 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Receptors, Interleukin-2 KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Receptors, Interleukin-2 -- biosynthesis KW - Bacterial Toxins -- therapeutic use KW - Treatment Outcome KW - Recombinant Proteins -- pharmacokinetics KW - Aged KW - Middle Aged KW - Pseudomonas aeruginosa KW - Exotoxins -- therapeutic use KW - Recombinant Proteins -- therapeutic use KW - Receptors, Interleukin-2 -- immunology KW - Male KW - Immunotoxins -- pharmacokinetics KW - Leukemia, Hairy Cell -- metabolism KW - Antineoplastic Agents -- pharmacokinetics KW - Leukemia, Hairy Cell -- drug therapy KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Leukemia, Hairy Cell -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69262559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Responses+in+refractory+hairy+cell+leukemia+to+a+recombinant+immunotoxin.&rft.au=Kreitman%2C+R+J%3BWilson%2C+W+H%3BRobbins%2C+D%3BMargulies%2C+I%3BStetler-Stevenson%2C+M%3BWaldmann%2C+T+A%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1999-11-15&rft.volume=94&rft.issue=10&rft.spage=3340&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-30 N1 - Date created - 1999-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Generation of Mature Dendritic Cells from a CD14 super(+) Cell Line (XS52) by IL-4, TNF- alpha , IL-1 beta , and Agonistic Anti-CD40 Monoclonal Antibody AN - 17443385; 4661016 AB - We established a model system to generate mature dendritic cells (DC) from a GM-CSF-dependent cell line, XS52, which had been isolated from the epidermis of newborn BALB/c mice. Screening of various soluble factors revealed that IL-4 induces phenotypic maturation of XS52 (as evaluated by enhanced expression of class II, CD40, CD80, CD86, CD11c, and loss of expression of CD14) in a time-dependent manner. The addition of TNF- alpha , IL-1 beta , and agonistic anti-CD40 mAb further enhanced expression of these maturation markers. Consistent with their phenotypic maturation, these cells (termed XS-DC) exhibited potent Ag-presenting capacity to both naive and primed T cells. In addition, injection of hapten-conjugated XS-DC induced contact hypersensitivity in vivo, suggesting their potential as tools for vaccination. Expression of CD14 by the starting cell population, the requirement for GM-CSF and IL-4, and the relatively long culture period are the common characteristics shared between our cells and human monocyte-derived DC, whose analogues in mice have not been identified. Because large numbers of skin-associated mature DC devoid of other cell lineages are easily obtained, this model system may facilitate the study of molecular events associated with maturation of DC and the use of DC for immunization. JF - Journal of Immunology AU - Yamada, N AU - Katz, SI AD - Dermatology Branch, National Cancer Institute, Building 10, Room 12N238, Bethesda, MD 20892, USA, skatz@box-s.nih.gov Y1 - 1999/11/15/ PY - 1999 DA - 1999 Nov 15 SP - 5331 EP - 5337 VL - 163 IS - 10 SN - 0022-1767, 0022-1767 KW - immunology KW - CD14 antigen KW - CD40 antigen KW - Interleukin 1 beta KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Interleukin 1b KW - Interleukin 1^b KW - Interleukin 4 KW - Monoclonal antibodies KW - Tumor necrosis factor-a KW - granulocyte-macrophage colony-stimulating factor KW - Dendritic cells KW - Tumor necrosis factor-^a KW - Cell lines KW - W3 33235:New cell lines KW - W 30965:Miscellaneous, Reviews KW - F 06742:General UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17443385?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Generation+of+Mature+Dendritic+Cells+from+a+CD14+super%28%2B%29+Cell+Line+%28XS52%29+by+IL-4%2C+TNF-+alpha+%2C+IL-1+beta+%2C+and+Agonistic+Anti-CD40+Monoclonal+Antibody&rft.au=Yamada%2C+N%3BKatz%2C+SI&rft.aulast=Yamada&rft.aufirst=N&rft.date=1999-11-15&rft.volume=163&rft.issue=10&rft.spage=5331&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Interleukin 4; Tumor necrosis factor-a; granulocyte-macrophage colony-stimulating factor; Cell lines; Monoclonal antibodies; Dendritic cells; Tumor necrosis factor-^a ER - TY - JOUR T1 - ErbB-2 kinase is required for constitutive stat 3 activation in malignant human lung epithelial cells. AN - 70790834; 10508495 AB - Overexpression of the growth factor receptor ErbB-2/Her2/Neu has been implicated in the development of non-small-cell lung cancer. We have reported that the transformation of human lung epithelial cells by c-erbB-2 also requires an active ErbB-1 (EGF receptor) and the autocrine production of its ligand, TGF-alpha. In this report, we demonstrate that STAT 3 is constitutively activated in these cells by the TGF-alpha-stimulated ErbB-1/-2 heterodimer complex. STAT 3 activation was confirmed by mobility shift assays and nuclear localization. ErbB-1 was required, but not sufficient for the TGF-alpha-induced activation of STATs. Inhibition of ErbB-2 kinase activity by tyrphostin AG825 prevented the constitutive activation of STAT 3 in the TGF-alpha-producing, ErbB-1 expressing cell line. Our results demonstrate a requirement for ErbB-2 kinase activity to establish constitutive STAT 3 activation resulting from an autocrine ErbB-1/ TGF-alpha loop. Int. J. Cancer 83:564-570, 1999. Published 1999 Wiley-Liss, Inc. JF - International journal of cancer AU - Fernandes, A AU - Hamburger, A W AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/11/12/ PY - 1999 DA - 1999 Nov 12 SP - 564 EP - 570 VL - 83 IS - 4 SN - 0020-7136, 0020-7136 KW - Benzothiazoles KW - 0 KW - DNA-Binding Proteins KW - Enzyme Inhibitors KW - Milk Proteins KW - STAT1 Transcription Factor KW - STAT1 protein, human KW - STAT3 Transcription Factor KW - STAT3 protein, human KW - STAT5 Transcription Factor KW - Trans-Activators KW - Transforming Growth Factor alpha KW - Tyrphostins KW - tyrphostin AG825 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Receptor, ErbB-2 KW - Index Medicus KW - Immunoblotting KW - Receptor, Epidermal Growth Factor -- metabolism KW - Cell Nucleus -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Dimerization KW - Humans KW - Precipitin Tests KW - Receptor, Epidermal Growth Factor -- genetics KW - Transfection KW - Enzyme Activation -- drug effects KW - Transforming Growth Factor alpha -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Tyrphostins -- pharmacology KW - Cell Line KW - Epithelial Cells -- metabolism KW - Trans-Activators -- metabolism KW - Receptor, ErbB-2 -- physiology KW - Receptor, ErbB-2 -- metabolism KW - Receptor, ErbB-2 -- antagonists & inhibitors KW - Lung Neoplasms -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70790834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=ErbB-2+kinase+is+required+for+constitutive+stat+3+activation+in+malignant+human+lung+epithelial+cells.&rft.au=Fernandes%2C+A%3BHamburger%2C+A+W%3BGerwin%2C+B+I&rft.aulast=Fernandes&rft.aufirst=A&rft.date=1999-11-12&rft.volume=83&rft.issue=4&rft.spage=564&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-18 N1 - Date created - 1999-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cocaine reward and MPTP toxicity: alteration by regional variant dopamine transporter overexpression AN - 17644780; 4631948 AB - Polygenic factors play important roles in animal models of substance abuse and susceptibility to dopaminergic neurodegeneration. Genetic factors are also likely to contribute to the etiology of human drug abuse disorders, and may alter human vulnerabilities to Parkinsonian neurodegeneration. The dopamine transporter (DAT; SLC6A3) is densely expressed by the dopaminergic midbrain neurons that play central roles in drug reward and is believed to be a primary site of action for cocaine reward. This transporter is necessary for the action of selective dopaminergic neurotoxins, and is uniquely expressed on neurons that are the primary targets of Parkinsonian neurodegeneration. To study possible influences of variant DAT expression on these processes, we have constructed transgenic mice (THDAT) in which tyrosine hydroxylase (TH) promoter sequences drive expression of a rat DAT cDNA variant, increase striatal DAT expression by 20-30%, and provide modest alterations in striatal levels of dopamine and its metabolites. THDAT mice habituate more rapidly to a novel environment than wildtype littermates. These animals display enhanced reward conferred by cocaine, as measured by conditioned place preference. However, locomotor responses to cocaine administration are similar to those of wildtype mice, except at high cocaine doses. THDAT mice display more than 50% greater losses of dopaminergic neurons following a course of MPTP treatment than do wildtype control mice. These results document a model for allelic variation at a gene locus that can exert significant effects in murine models of human substance abuse vulnerability and dopaminergic neurodegeneration. JF - Molecular Brain Research AU - Donovan, D M AU - Miner, L L AU - Perry, M P AU - Revay, R S AU - Sharpe, L G AU - Przedborski, S AU - Kostic, V AU - Philpot, R M AU - Kirstein, CL AU - Rothman, R B AU - Schindler, C W AU - Uhl, G R AD - Molecular Neurobiology, Intramural Research Program, National Institute on Drug Abuse, NIH, Baltimore, MD USA Y1 - 1999/11/10/ PY - 1999 DA - 1999 Nov 10 SP - 37 EP - 49 PB - Elsevier VL - 73 IS - 1-2 SN - 0169-328X, 0169-328X KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - MPTP KW - Transgenic mice KW - Dopamine transporter KW - Neostriatum KW - Neurotoxicity KW - Reinforcement KW - Tyrosine 3-monooxygenase KW - Cocaine KW - X 24180:Social poisons & drug abuse KW - N3 11139:Toxicological and psychoactive drug correlates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17644780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Brain+Research&rft.atitle=Cocaine+reward+and+MPTP+toxicity%3A+alteration+by+regional+variant+dopamine+transporter+overexpression&rft.au=Donovan%2C+D+M%3BMiner%2C+L+L%3BPerry%2C+M+P%3BRevay%2C+R+S%3BSharpe%2C+L+G%3BPrzedborski%2C+S%3BKostic%2C+V%3BPhilpot%2C+R+M%3BKirstein%2C+CL%3BRothman%2C+R+B%3BSchindler%2C+C+W%3BUhl%2C+G+R&rft.aulast=Donovan&rft.aufirst=D&rft.date=1999-11-10&rft.volume=73&rft.issue=1-2&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Molecular+Brain+Research&rft.issn=0169328X&rft_id=info:doi/10.1016%2FS0169-328X%2899%2900235-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Reinforcement; MPTP; Neurotoxicity; Neostriatum; Dopamine transporter; Tyrosine 3-monooxygenase; Transgenic mice DO - http://dx.doi.org/10.1016/S0169-328X(99)00235-1 ER - TY - JOUR T1 - cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene AN - 17413762; 4635406 AB - Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated muscle characterized in 60% of cases by a t(2; 13)(q35; q14). This results in the fusion of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-FKHR gene possesses transforming properties; however, the effects of this chimeric oncogene on gene expression are largely unknown. To investigate the actions of these transcription factors, both Pax3 and PAX3-FKHR were introduced into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a murine cDNA microarray containing 2,225 elements. We found that PAX3-FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factors MyoD, Myogenin, Six1, and Slug as well as a battery of genes involved in several aspects of muscle function. Notable among this group were the growth factor gene Igf2 and its binding protein Igfbp5. Relevance of this model was suggested by verification that three of these genes (IGFBP5, HSIX1, and Slug) were also expressed in alveolar rhabdomyosarcoma cell lines. This study utilizes cDNA microarrays to elucidate the pattern of gene expression induced by an oncogenic transcription factor and demonstrates the profound myogenic properties of PAX3-FKHR in NIH 3T3 cells. JF - Proceedings of the National Academy of Sciences, USA AU - Khan, J AU - Bittner, M L AU - Saal, L H AU - Teichmann, U AU - Azorsa, DO AU - Gooden, G C AU - Pavan, W J AU - Trent, J M AU - Meltzer, P S AD - Cancer Genetics Branch and Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 USA, pmeltzer@nhgri.nih.gov Y1 - 1999/11/09/ PY - 1999 DA - 1999 Nov 09 SP - 13264 EP - 13269 VL - 96 IS - 23 SN - 0027-8424, 0027-8424 KW - mice KW - cDNA microarrays KW - NIH3T3 cells KW - Slug protein KW - Six1 protein KW - DNA microarrays KW - FKHR gene KW - HSIX1 gene KW - IGFBP5 gene KW - Igf2 gene KW - MyoD gene KW - MyoD protein KW - Myogenin KW - Myogenin gene KW - PAX3 gene KW - Six1 gene KW - Slug gene KW - rhabdomyosarcoma KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Oncogenes & Growth Factors Abstracts; Genetics Abstracts KW - Limbs KW - Transcription factors KW - Fusion protein KW - G 07397:Rodentia (mice) KW - W3 33243:Molecular methods KW - B 26240:Other nuclear oncogenes & binding proteins KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17413762?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=cDNA+microarrays+detect+activation+of+a+myogenic+transcription+program+by+the+PAX3-FKHR+fusion+oncogene&rft.au=Khan%2C+J%3BBittner%2C+M+L%3BSaal%2C+L+H%3BTeichmann%2C+U%3BAzorsa%2C+DO%3BGooden%2C+G+C%3BPavan%2C+W+J%3BTrent%2C+J+M%3BMeltzer%2C+P+S&rft.aulast=Khan&rft.aufirst=J&rft.date=1999-11-09&rft.volume=96&rft.issue=23&rft.spage=13264&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.23.13264 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transcription factors; Fusion protein; Limbs DO - http://dx.doi.org/10.1073/pnas.96.23.13264 ER - TY - JOUR T1 - Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. AN - 69274861; 10556521 AB - Two sodium-dependent vitamin C transporters, hSVCT1 and hSVCT2, were cloned from a human kidney cDNA library. hSVCT1 had a 1797 bp open reading frame encoding a 598 amino acid polypeptide. The 1953 bp open reading frame of hSVCT2 encoded a 650 amino acid polypeptide. Using a Xenopus laevis oocyte expression system, both transporters were functionally expressed. By Eadie-Hofstee transformation the apparent K(m) of hSVCT1 for ascorbate was 252.0 microM and of hSVCT2 for ascorbate was 21.3 microM. Both transporters were sodium-dependent and did not transport dehydroascorbic acid. Incubation of oocytes expressing either transporter with phorbol 12-myristate 13-acetate (PMA) inhibited ascorbate transport activity. Availability of the human transporter clones may facilitate new strategies for determining vitamin C intake. JF - FEBS letters AU - Daruwala, R AU - Song, J AU - Koh, W S AU - Rumsey, S C AU - Levine, M AD - Molecular and Clinical Nutrition Section, Bldg. 10, Rm. 4D52, MSC 1372, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1372, USA. Y1 - 1999/11/05/ PY - 1999 DA - 1999 Nov 05 SP - 480 EP - 484 VL - 460 IS - 3 SN - 0014-5793, 0014-5793 KW - Carrier Proteins KW - 0 KW - Organic Anion Transporters, Sodium-Dependent KW - Proteins KW - Sodium-Coupled Vitamin C Transporters KW - Symporters KW - Bucladesine KW - 63X7MBT2LQ KW - Sodium KW - 9NEZ333N27 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Index Medicus KW - Animals KW - Protein Biosynthesis KW - Humans KW - Biological Transport KW - Amino Acid Sequence KW - Bucladesine -- pharmacology KW - Cloning, Molecular KW - Xenopus laevis KW - Base Sequence KW - Oocytes -- metabolism KW - Molecular Sequence Data KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Female KW - Proteins -- chemistry KW - Carrier Proteins -- chemistry KW - Sodium -- physiology KW - Carrier Proteins -- genetics KW - Carrier Proteins -- physiology KW - Ascorbic Acid -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology KW - Carrier Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69274861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Cloning+and+functional+characterization+of+the+human+sodium-dependent+vitamin+C+transporters+hSVCT1+and+hSVCT2.&rft.au=Daruwala%2C+R%3BSong%2C+J%3BKoh%2C+W+S%3BRumsey%2C+S+C%3BLevine%2C+M&rft.aulast=Daruwala&rft.aufirst=R&rft.date=1999-11-05&rft.volume=460&rft.issue=3&rft.spage=480&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-22 N1 - Date created - 1999-12-22 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AJ269477; GENBANK; AJ269478 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Calcium-antagonist drugs. AN - 69203384; 10547409 JF - The New England journal of medicine AU - Abernethy, D R AU - Schwartz, J B AD - Division of Clinical Pharmacolgy, Georgetown University Medical Center, Washington, DC, USA. abernethyd@grc.nia.nih.gov Y1 - 1999/11/04/ PY - 1999 DA - 1999 Nov 04 SP - 1447 EP - 1457 VL - 341 IS - 19 SN - 0028-4793, 0028-4793 KW - Calcium Channel Blockers KW - 0 KW - Calcium Channels KW - Abridged Index Medicus KW - Index Medicus KW - Drug Interactions KW - Calcium Channels -- physiology KW - Angina Pectoris -- drug therapy KW - Humans KW - Calcium Channels -- chemistry KW - Arrhythmias, Cardiac -- drug therapy KW - Myocardial Infarction -- drug therapy KW - Hypertension -- drug therapy KW - Calcium Channel Blockers -- contraindications KW - Calcium Channel Blockers -- pharmacology KW - Cardiovascular Diseases -- drug therapy KW - Calcium Channel Blockers -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69203384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Calcium-antagonist+drugs.&rft.au=Abernethy%2C+D+R%3BSchwartz%2C+J+B&rft.aulast=Abernethy&rft.aufirst=D&rft.date=1999-11-04&rft.volume=341&rft.issue=19&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. AN - 69235817; 10547390 AB - In response to findings from the Breast Cancer Prevention Trial that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of tamoxifen. Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks. Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of tamoxifen treatment. Data on the effects of tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of tamoxifen. The risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. In particular, the absolute risks from tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of tamoxifen and to identify classes of women for whom the benefits outweigh the risks. Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of tamoxifen for reducing breast cancer risk. JF - Journal of the National Cancer Institute AU - Gail, M H AU - Costantino, J P AU - Bryant, J AU - Croyle, R AU - Freedman, L AU - Helzlsouer, K AU - Vogel, V AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. gailm@exchange.nih.gov Y1 - 1999/11/03/ PY - 1999 DA - 1999 Nov 03 SP - 1829 EP - 1846 VL - 91 IS - 21 SN - 0027-8874, 0027-8874 KW - Anticarcinogenic Agents KW - 0 KW - Estrogen Receptor Modulators KW - Selective Estrogen Receptor Modulators KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - AIDS/HIV KW - United States KW - Neoplasm Invasiveness KW - Fractures, Bone -- prevention & control KW - Age Factors KW - Fractures, Bone -- epidemiology KW - Venous Thrombosis -- chemically induced KW - Humans KW - Counseling KW - Controlled Clinical Trials as Topic KW - Risk KW - Patient Education as Topic KW - Education KW - Endometrial Neoplasms -- chemically induced KW - Risk Factors KW - Carcinoma in Situ KW - Pulmonary Embolism -- chemically induced KW - Cataract -- prevention & control KW - National Institutes of Health (U.S.) KW - Stroke -- chemically induced KW - Female KW - Anticarcinogenic Agents -- therapeutic use KW - Breast Neoplasms -- pathology KW - Tamoxifen -- therapeutic use KW - Selective Estrogen Receptor Modulators -- adverse effects KW - Selective Estrogen Receptor Modulators -- therapeutic use KW - Tamoxifen -- adverse effects KW - Estrogen Receptor Modulators -- therapeutic use KW - Breast Neoplasms -- prevention & control KW - Anticarcinogenic Agents -- adverse effects KW - Estrogen Receptor Modulators -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69235817?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Weighing+the+risks+and+benefits+of+tamoxifen+treatment+for+preventing+breast+cancer.&rft.au=Gail%2C+M+H%3BCostantino%2C+J+P%3BBryant%2C+J%3BCroyle%2C+R%3BFreedman%2C+L%3BHelzlsouer%2C+K%3BVogel%2C+V&rft.aulast=Gail&rft.aufirst=M&rft.date=1999-11-03&rft.volume=91&rft.issue=21&rft.spage=1829&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-30 N1 - Date created - 1999-11-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Natl Cancer Inst. 2000 May 3;92(9):757-8 [10793117] J Natl Cancer Inst. 1999 Nov 3;91(21):1792-3 [10547378] J Natl Cancer Inst. 2000 Apr 19;92(8):657-9 [10772687] Erratum In: J Natl Cancer Inst 2000 Feb 2;92(3):275 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The NIDCD's clinical trials cooperative groups: a brief overview. AN - 85316780; pmid-10565711 AB - The National Institute on Deafness and Other Communication Disorders (NIDCD) embarked on the establishment of two clinical trials cooperative groups in October 1996 in response to a scientific research need. It intended that the clinical trials cooperative groups (CTCGs) design and implement clinical trial protocols capable of addressing the efficacy of therapeutic interventions for diseases and disorders of human communication. Most commonly, owing to the substantial number of patients required, the trials are expected to involve multiple study sites, with each study site adhering to a uniform study protocol, standardized treatment regimens, and prescribed data collection procedures. A complex administrative structure is required to coordinate the activities of the CTCGs and to assure compliance with a myriad of government regulations. Similarly, participating study sites must meet stringent requirements including leadership by an individual experienced in clinical trials. There is a relative dearth of experienced clinical trialists dedicated to research in human communication. This article details the complexities involved in the conduct of multicenter clinical trials and the NIDCD's efforts to promote clinical trials activities and to develop clinical trials training opportunities. JF - The American journal of otology AU - Gulya, A J AD - National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 705 EP - 708 VL - 20 IS - 6 SN - 0192-9763, 0192-9763 KW - Index Medicus KW - National Library of Medicine KW - Humans KW - Deafness KW - Clinical Trials as Topic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85316780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+otology&rft.atitle=The+NIDCD%27s+clinical+trials+cooperative+groups%3A+a+brief+overview.&rft.au=Gulya%2C+A+J&rft.aulast=Gulya&rft.aufirst=A&rft.date=1999-11-01&rft.volume=20&rft.issue=6&rft.spage=705&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+otology&rft.issn=01929763&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A functional lesion in developmental dyslexia: left angular gyral blood flow predicts severity. AN - 85316480; pmid-10550226 AB - Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p <.01), but with worse reading skill in dyslexia (p <.01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia. (Copyright 1999 Academic Press.) JF - Brain and language AU - Rumsey, J M AU - Horwitz, B AU - Donohue, B C AU - Nace, K L AU - Maisog, J M AU - Andreason, P AD - Child Psychiatry Branch, National Institute of Mental Health, Bethesda,MD 20892, USA. jrumsey@box-j.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 187 EP - 204 VL - 70 IS - 2 SN - 0093-934X, 0093-934X KW - Index Medicus KW - National Library of Medicine KW - Wechsler Scales KW - Cognition -- physiology KW - Severity of Illness Index KW - Humans KW - Adult KW - Tomography, Emission-Computed KW - Predictive Value of Tests KW - Adolescent KW - Male KW - Functional Laterality -- physiology KW - Fixation, Ocular -- physiology KW - Brain -- radionuclide imaging KW - Brain -- blood supply KW - Dyslexia -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85316480?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+language&rft.atitle=A+functional+lesion+in+developmental+dyslexia%3A+left+angular+gyral+blood+flow+predicts+severity.&rft.au=Rumsey%2C+J+M%3BHorwitz%2C+B%3BDonohue%2C+B+C%3BNace%2C+K+L%3BMaisog%2C+J+M%3BAndreason%2C+P&rft.aulast=Rumsey&rft.aufirst=J&rft.date=1999-11-01&rft.volume=70&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Brain+and+language&rft.issn=0093934X&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Capability of serum to convert streptomycin to cytotoxin in patients with aminoglycoside-induced hearing loss. AN - 85316059; pmid-10545628 AB - Individual variations in sensitivity to the ototoxic effects of aminoglycoside antibiotics are well documented. Our research demonstrates that there is an apparent difference in serum from patients who are resistant or susceptible to aminoglycoside ototoxicity. In the first study, the cytotoxicity of sera from patients with and without hearing loss after various time periods following the discontinuation of aminoglycoside treatment was assayed using the isolated outer hair cell toxicity assay. The results indicate that sera from patients with hearing loss were significantly more toxic than sera from patients with normal hearing or minimal hearing loss. This toxicity may persist for up to 1 year after discontinuation of aminoglycoside therapy. In a second study, sera were obtained from patients who had received aminoglycoside therapy several years previously. None of these sera was toxic to isolated outer hair cells in vitro. Streptomycin was then incubated with the sera or a protein fraction isolated from sera, and the incubation mixtures were tested for toxicity. The percentage of damaged outer hair cells was significantly higher when streptomycin had been treated with sera or a serum protein fraction from patients with hearing loss (58+/-10% and 68+/-9%, respectively) than with sera or a serum protein fraction from a control group (10+/-5% and 17+/-4%, respectively). In addition, several incubation mixtures were analyzed using high performance liquid chromatography. A new chromatographic peak was only found in the incubations of streptomycin with serum protein from patients with hearing loss. The results suggest that sera from individuals sensitive to aminoglycoside antibiotics may metabolize these drugs to cytotoxins. JF - Hearing research AU - Wang, S AU - Bian, Q AU - Liu, Z AU - Feng, Y AU - Lian, N AU - Chen, H AU - Hu, C AU - Dong, Y AU - Cai, Z AD - Beijing Institute of Otorhinolaryngology, 17# Hougou Lane Chong-Nei, Beijing, PR China. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1 EP - 7 VL - 137 IS - 1-2 SN - 0378-5955, 0378-5955 KW - Index Medicus KW - National Library of Medicine KW - Animals KW - Guinea Pigs KW - Humans KW - Child KW - Hair Cells, Auditory, Outer -- drug effects KW - Cell Survival -- drug effects KW - Adult KW - Middle Aged KW - Blood Proteins -- metabolism KW - Adolescent KW - Female KW - Hair Cells, Auditory, Outer -- pathology KW - Male KW - Deafness -- blood KW - Streptomycin -- adverse effects KW - Cytotoxins -- blood KW - Deafness -- chemically induced KW - Anti-Bacterial Agents -- adverse effects KW - Streptomycin -- toxicity KW - Anti-Bacterial Agents -- blood KW - Anti-Bacterial Agents -- toxicity KW - Streptomycin -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85316059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hearing+research&rft.atitle=Capability+of+serum+to+convert+streptomycin+to+cytotoxin+in+patients+with+aminoglycoside-induced+hearing+loss.&rft.au=Wang%2C+S%3BBian%2C+Q%3BLiu%2C+Z%3BFeng%2C+Y%3BLian%2C+N%3BChen%2C+H%3BHu%2C+C%3BDong%2C+Y%3BCai%2C+Z&rft.aulast=Wang&rft.aufirst=S&rft.date=1999-11-01&rft.volume=137&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Hearing+research&rft.issn=03785955&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Associative learning impairments in patients with frontal lobe damage. AN - 85312788; pmid-10590820 AB - The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The FLD patients were moderately impaired on the free recall condition only but there was a subgroup of FLD patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall. JF - Brain and cognition AU - Dimitrov, M AU - Granetz, J AU - Peterson, M AU - Hollnagel, C AU - Alexander, G AU - Grafman, J AD - Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1440, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 213 EP - 230 VL - 41 IS - 2 SN - 0278-2626, 0278-2626 KW - Index Medicus KW - National Library of Medicine KW - Severity of Illness Index KW - Analysis of Variance KW - Humans KW - Aged KW - Mental Recall KW - Wechsler Scales KW - Memory Disorders -- diagnosis KW - Aged, 80 and over KW - Memory Disorders -- etiology KW - Adult KW - Cues KW - Middle Aged KW - Male KW - Female KW - Temporal Lobe -- physiopathology KW - Frontal Lobe -- physiopathology KW - Association Learning -- physiology KW - Dementia -- complications KW - Dementia -- physiopathology KW - Learning Disorders -- etiology KW - Learning Disorders -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85312788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+and+cognition&rft.atitle=Associative+learning+impairments+in+patients+with+frontal+lobe+damage.&rft.au=Dimitrov%2C+M%3BGranetz%2C+J%3BPeterson%2C+M%3BHollnagel%2C+C%3BAlexander%2C+G%3BGrafman%2C+J&rft.aulast=Dimitrov&rft.aufirst=M&rft.date=1999-11-01&rft.volume=41&rft.issue=2&rft.spage=213&rft.isbn=&rft.btitle=&rft.title=Brain+and+cognition&rft.issn=02782626&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cross-language positive priming disappears, negative priming does not: evidence for two sources of selective inhibition. AN - 85307407; pmid-10586580 AB - The authors used a unilingual and bilingual primed lexical decision task to investigate priming effects produced by attended and ignored words. In the unilingual experiment, accelerated lexical decisions to probe target words resulted when the word matched the preceding target word, whereas slowed lexical decisions to probe target words resulted when the word matched the preceding ignored nontarget word. In the bilingual (English-Spanish) experiment, between-language, rather than within-language, priming manipulations were used. Although the ignored repetition negative priming effect replicated across languages, cross-language attended repetition positive priming did not. This dissociation of priming effects in the inter- versus intralanguage priming conditions contradicts episodic retrieval accounts of negative priming that deny the existence of selective inhibitory processes. On the other hand, these results support an extension of inhibition-based accounts of negative priming, because they indicate that inhibition can operate at two levels of abstraction--local word and global language--simultaneously. JF - Memory & cognition AU - Neumann, E AU - McCloskey, M S AU - Felio, A C AD - National Institute of Mental Health, Bethesda, Maryland, USA. e.neumann@psyc.canterbury.ac.nz Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1051 EP - 1063 VL - 27 IS - 6 SN - 0090-502X, 0090-502X KW - Index Medicus KW - National Library of Medicine KW - Psycholinguistics KW - Humans KW - Adult KW - Decision Making KW - Paired-Associate Learning KW - Female KW - Male KW - Verbal Learning KW - Mental Recall KW - Attention KW - Multilingualism KW - Inhibition (Psychology) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85307407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Buspirone+treatment+of+alcoholism%3A+age+of+onset%2C+and+cerebrospinal+fluid+5-hydroxyindolacetic+acid+and+homovanillic+acid+concentrations%2C+but+not+medication+treatment%2C+predict+return+to+drinking.&rft.au=George%2C+D+T%3BRawlings%2C+R%3BEckardt%2C+M+J%3BPhillips%2C+M+J%3BShoaf%2C+S+E%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1999-02-01&rft.volume=23&rft.issue=2&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Review of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) of head and neck. AN - 85298099; pmid-10579239 AB - The entity known as sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RD disease), is an uncommon benign proliferation of hematopoietic and fibrous tissue that often presents in the head and neck region. Its initial manifestations most often include a roughly symmetric, painless, bilateral cervical adenopathy, although extranodal disease may develop in a minority of patients. The key histologic feature of SHML is the presence of various numbers of large, pale histiocytic cells that contain within their cellular borders apparently engulfed lymphocytes ("emperipolesis"); these distinctive large, pale cells - RD cells - are S-100 protein-positive by immunostaining and so differ from ordinary histiocytes. Despite its sometimes impressive clinical presentation, SHML is a benign and self-limited disease, whose treatment is aimed largely at controlling its local manifestations (most often by surgical therapy). The microscopic differential diagnosis, particularly in extranodal disease, is at times challenging and can include Langerhans' cell histiocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, metastatic carcinoma, and metastatic malignant melanoma. JF - The Annals of otology, rhinology, and laryngology AU - Carbone, A AU - Passannante, A AU - Gloghini, A AU - Devaney, K O AU - Rinaldo, A AU - Ferlito, A AD - Division of Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1095 EP - 1104 VL - 108 IS - 11 Pt 1 SN - 0003-4894, 0003-4894 KW - Abridged Index Medicus; Index Medicus KW - National Library of Medicine KW - Histiocytosis, Sinus -- therapy KW - Histiocytes -- metabolism KW - Diagnosis, Differential KW - Head KW - Humans KW - Histiocytes -- pathology KW - Neck KW - Histiocytosis, Sinus -- pathology KW - Histiocytosis, Sinus -- epidemiology KW - Antigens, CD1 -- metabolism KW - S100 Proteins -- metabolism KW - Antigens, Surface -- metabolism KW - Immunohistochemistry KW - Lymph Nodes -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85298099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Review+of+sinus+histiocytosis+with+massive+lymphadenopathy+%28Rosai-Dorfman+disease%29+of+head+and+neck.&rft.au=Carbone%2C+A%3BPassannante%2C+A%3BGloghini%2C+A%3BDevaney%2C+K+O%3BRinaldo%2C+A%3BFerlito%2C+A&rft.aulast=Carbone&rft.aufirst=A&rft.date=1999-11-01&rft.volume=108&rft.issue=11+Pt+1&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin. AN - 85276639; pmid-10533028 AB - An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc. JF - American Journal of Medical Genetics AU - Lacbawan, F L AU - White, B J AU - Anguiano, A AU - Rigdon, D T AU - Ball, K D AU - Bromage, G B AU - Yang, X AU - DiFazio, M P AU - Levin, S W AD - Medical Genetics Branch, NHGRI, the National Institutes of Health, Bethesda, Maryland, USA. PY - 1999 SP - 139 EP - 142 VL - 87 IS - 2 SN - 0148-7299, 0148-7299 KW - Karyotyping KW - Centromere KW - Human KW - In Situ Hybridization, Fluorescence KW - Child, Preschool KW - Infant KW - Chromosomes, Human, Pair 2 KW - Adult KW - Abnormalities, Multiple KW - Case Report KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Chromosome Deletion KW - Fathers KW - Inversion (Genetics) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85276639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-selected+mutagenesis+of+a+conserved+nucleotide+binding+HXGH+motif+located+in+the+ATP+sulfurylase+domain+of+human+bifunctional+3%27-phosphoadenosine+5%27-phosphosulfate+synthase.&rft.au=Venkatachalam%2C+K+V%3BFuda%2C+H%3BKoonin%2C+E+V%3BStrott%2C+C+A&rft.aulast=Venkatachalam&rft.aufirst=K&rft.date=1999-01-29&rft.volume=274&rft.issue=5&rft.spage=2601&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Response to motion in extrastriate area MSTl: disparity sensitivity. AN - 85239806; pmid-10561419 AB - Many neurons in the lateral-ventral region of the medial superior temporal area (MSTl) have a clear center surround separation in their receptive fields. Either moving or stationary stimuli in the surround modulates the response to moving stimuli in the center, and this modulation could facilitate the perceptual segmentation of a moving object from its background. Another mechanism that could facilitate such segmentation would be sensitivity to binocular disparity in the center and surround regions of the receptive fields of these neurons. We therefore investigated the sensitivity of these MSTl neurons to disparity ranging from three degrees crossed disparity (near) to three degrees uncrossed disparity (far) applied to both the center and the surround regions. Many neurons showed clear disparity sensitivity to stimulus motion in the center of the receptive field. About (1)/(3) of 104 neurons had a clear peak in their response, whereas another (1)/(3) had broader tuning. Monocular stimulation abolished the tuning. The prevalence of cells broadly tuned to near and far disparity and the reversal of preferred directions at different disparities observed in MSTd were not found in MSTl. A stationary surround at zero disparity simply modulated up or down the response to moving stimuli at different disparities in the receptive field (RF) center but did not alter the disparity tuning curve. When the RF center motion was held at zero disparity and the disparity of the stationary surround was varied, some surround disparities produced greater modulation of MSTl neuron response than did others. Some neurons with different disparity preferences in center and surround responded best to the relative disparity differences between center and surround, whereas others were related to the absolute difference between center and surround. The combination of modulatory surrounds and the sensitivity to relative difference between center and surround disparity make these MSTl neurons particularly well suited for the segmentation of a moving object from the background. JF - Journal of Neurophysiology AU - Eifuku, S AU - Wurtz, R H AD - Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA. PY - 1999 SP - 2462 EP - 2475 VL - 82 IS - 5 SN - 0022-3077, 0022-3077 KW - Visual Cortex KW - Regression Analysis KW - Analysis of Variance KW - Animal KW - Visual Fields KW - Motion Perception KW - Brain Mapping KW - Photic Stimulation KW - Vision Disparity KW - Neurons KW - Color Perception KW - Macaca mulatta KW - Male UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85239806?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Neurophysiology&rft.atitle=Response+to+motion+in+extrastriate+area+MSTl%3A+disparity+sensitivity.&rft.au=Eifuku%2C+S%3BWurtz%2C+R+H&rft.aulast=Eifuku&rft.aufirst=S&rft.date=1999-11-01&rft.volume=82&rft.issue=5&rft.spage=2462&rft.isbn=&rft.btitle=&rft.title=Journal+of+Neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine. AN - 70832528; 10525111 AB - Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase. JF - The Journal of pharmacology and experimental therapeutics AU - Kitchen, B J AU - Moser, A AU - Lowe, E AU - Balis, F M AU - Widemann, B AU - Anderson, L AU - Strong, J AU - Blaney, S M AU - Berg, S L AU - O'Brien, M AU - Adamson, P C AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 870 EP - 874 VL - 291 IS - 2 SN - 0022-3565, 0022-3565 KW - 8-hydroxythioguanine KW - 0 KW - Antimetabolites, Antineoplastic KW - Aldehyde Oxidoreductases KW - EC 1.2.- KW - Aldehyde Oxidase KW - EC 1.2.3.1 KW - Thioguanine KW - FTK8U1GZNX KW - Index Medicus KW - Mass Spectrometry KW - Infusions, Intravenous KW - Humans KW - In Vitro Techniques KW - Child KW - Chromatography, High Pressure Liquid KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Aldehyde Oxidoreductases -- physiology KW - Thioguanine -- blood KW - Thioguanine -- administration & dosage KW - Antimetabolites, Antineoplastic -- blood KW - Thioguanine -- analogs & derivatives KW - Antimetabolites, Antineoplastic -- metabolism KW - Thioguanine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832528?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Thioguanine+administered+as+a+continuous+intravenous+infusion+to+pediatric+patients+is+metabolized+to+the+novel+metabolite+8-hydroxy-thioguanine.&rft.au=Kitchen%2C+B+J%3BMoser%2C+A%3BLowe%2C+E%3BBalis%2C+F+M%3BWidemann%2C+B%3BAnderson%2C+L%3BStrong%2C+J%3BBlaney%2C+S+M%3BBerg%2C+S+L%3BO%27Brien%2C+M%3BAdamson%2C+P+C&rft.aulast=Kitchen&rft.aufirst=B&rft.date=1999-11-01&rft.volume=291&rft.issue=2&rft.spage=870&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-24 N1 - Date created - 1999-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene targeted DNA double-strand break induction by (125)I-labeled triplex-forming oligonucleotides is highly mutagenic following repair in human cells. AN - 70803664; 10518622 AB - A parallel binding motif 16mer triplex-forming oligonucleotide (TFO) complementary to a polypurine-polypyrimidine target region near the 3'-end of the SupF gene of plasmid pSP189 was labeled with [5-(125)I]dCMP at position 15. Following triplex formation and decay accumulation, radiation-induced site-specific double-strand breaks (DSBs) were produced in the pSP189 SupF gene. Bulk damaged DNA and the isolated site-specific DSB-containing DNA were separately transfected into human WI38VA13 cells and allowed to repair prior to recovery and analysis of mutants. Bulk damaged DNA had a relatively low mutation frequency of 2.7 x 10(-3). In contrast, the isolated linear DNA containing site-specific DSBs had an unusually high mutation frequency of 7.9 x 10(-1). This was nearly 300-fold greater than that observed for the bulk damaged DNA mixture, and >1.5 x 10(4)-fold greater than background. The mutation spectra displayed a high proportion of deletion mutants targeted to the(125)I binding position within the SupF gene for both bulk damaged DNA and isolated linear DNA. Both spectra were characterized by complex mutations with mixtures of changes. However, mutations recovered from the linear site-specific DSB-containing DNA presented a much higher proportion of complex deletion mutations. JF - Nucleic acids research AU - Mezhevaya, K AU - Winters, T A AU - Neumann, R D AD - Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/11/01/ PY - 1999 DA - 1999 Nov 01 SP - 4282 EP - 4290 VL - 27 IS - 21 KW - Iodine Radioisotopes KW - 0 KW - Oligodeoxyribonucleotides KW - supF tRNA KW - triplex DNA KW - Bleomycin KW - 11056-06-7 KW - DNA KW - 9007-49-2 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Bleomycin -- pharmacology KW - Nucleic Acid Conformation -- radiation effects KW - Plasmids -- metabolism KW - Plasmids -- genetics KW - DNA Mutational Analysis KW - Humans KW - Nucleic Acid Hybridization KW - Base Sequence KW - RNA, Transfer -- genetics KW - Transfection KW - Molecular Sequence Data KW - Iodine Radioisotopes -- metabolism KW - Plasmids -- chemistry KW - Gene Dosage KW - Gene Targeting KW - Genes, Suppressor KW - Nucleic Acid Conformation -- drug effects KW - Cell Line KW - Mutation -- drug effects KW - DNA -- metabolism KW - Mutagenesis, Site-Directed -- genetics KW - Oligodeoxyribonucleotides -- genetics KW - Mutagenesis, Site-Directed -- radiation effects KW - Mutation -- radiation effects KW - DNA Damage -- genetics KW - DNA Damage -- drug effects KW - DNA Repair -- genetics KW - DNA Repair -- radiation effects KW - DNA -- genetics KW - Mutation -- genetics KW - Oligodeoxyribonucleotides -- metabolism KW - DNA Damage -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70803664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Gene+targeted+DNA+double-strand+break+induction+by+%28125%29I-labeled+triplex-forming+oligonucleotides+is+highly+mutagenic+following+repair+in+human+cells.&rft.au=Mezhevaya%2C+K%3BWinters%2C+T+A%3BNeumann%2C+R+D&rft.aulast=Mezhevaya&rft.aufirst=K&rft.date=1999-11-01&rft.volume=27&rft.issue=21&rft.spage=4282&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-02 N1 - Date created - 1999-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiopharmaceuticals and their use in the current practice of nuclear medicine. AN - 69493759; 10889704 JF - Lippincott's primary care practice AU - Fejka, R M AD - Department of Nuclear Medicine, National Institutes of Health, Bethesda, Maryland 20892-1180, USA. PY - 1999 SP - 531 EP - 545 VL - 3 IS - 6 SN - 1088-5471, 1088-5471 KW - Radiopharmaceuticals KW - 0 KW - Nursing KW - Radiation Dosage KW - Humans KW - Primary Health Care KW - Radionuclide Imaging KW - Radiopharmaceuticals -- supply & distribution KW - Nuclear Medicine -- trends KW - Neoplasms -- diagnostic imaging KW - Nuclear Medicine -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69493759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lippincott%27s+primary+care+practice&rft.atitle=Radiopharmaceuticals+and+their+use+in+the+current+practice+of+nuclear+medicine.&rft.au=Fejka%2C+R+M&rft.aulast=Fejka&rft.aufirst=R&rft.date=1999-11-01&rft.volume=3&rft.issue=6&rft.spage=531&rft.isbn=&rft.btitle=&rft.title=Lippincott%27s+primary+care+practice&rft.issn=10885471&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-03 N1 - Date created - 2000-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel JC virus variant found in the Highlands of Papua New Guinea has a 21-base pair deletion in the agnoprotein gene. AN - 69468848; 10774552 AB - This paper describes a unique JC virus (JCV) variant recovered from the Highlands of Papua New Guinea that contains an inframe 21-bp deletion in the agnoprotein gene. We characterize the mutation and suggest possible roles for the deletion in JCV evolution. JCV DNA was extracted from urine and polymerase chain reaction (PCR) amplified using whole genome primers. PCR products were cloned, and multiple clones were sequenced. The JCV agnogene was PCR amplified to verify the presence of the agnogene deletion. This mutation creates a 21-bp deletion near the 3' end, which alters the predicted secondary structure of the messenger RNA and changes local codon usage at the 3' end of the agnogene. Protein secondary structure predictions suggest the deleted portion of the agnoprotein may be a flexible surface feature. We describe the first stable coding region deletion in JCV that presumably signifies a single evolutionary event that led to the split from other Highlands viral groups and occurred well after the human expansions that led to the peopling of the Southwest Pacific. JF - Journal of human virology AU - Jobes, D V AU - Friedlaender, J S AU - Mgone, C S AU - Koki, G AU - Alpers, M P AU - Ryschkewitsch, C F AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. PY - 1999 SP - 350 EP - 358 VL - 2 IS - 6 SN - 1090-9508, 1090-9508 KW - Codon KW - 0 KW - DNA, Viral KW - RNA, Messenger KW - RNA, Viral KW - Viral Proteins KW - Viral Regulatory and Accessory Proteins KW - agnoprotein, polyomavirus KW - Index Medicus KW - Protein Structure, Secondary KW - Tumor Virus Infections -- virology KW - Codon -- genetics KW - Humans KW - RNA, Messenger -- chemistry KW - Sequence Analysis, DNA KW - RNA, Messenger -- genetics KW - Nucleic Acid Conformation KW - Evolution, Molecular KW - Polymerase Chain Reaction KW - Base Sequence KW - RNA, Messenger -- metabolism KW - Papua New Guinea KW - RNA, Viral -- chemistry KW - Molecular Sequence Data KW - DNA, Viral -- urine KW - RNA, Viral -- genetics KW - RNA, Viral -- metabolism KW - Emigration and Immigration KW - Viral Proteins -- genetics KW - Genetic Variation KW - JC Virus -- genetics KW - Viral Proteins -- chemistry KW - Papillomavirus Infections -- virology KW - JC Virus -- isolation & purification KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69468848?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+human+virology&rft.atitle=A+novel+JC+virus+variant+found+in+the+Highlands+of+Papua+New+Guinea+has+a+21-base+pair+deletion+in+the+agnoprotein+gene.&rft.au=Jobes%2C+D+V%3BFriedlaender%2C+J+S%3BMgone%2C+C+S%3BKoki%2C+G%3BAlpers%2C+M+P%3BRyschkewitsch%2C+C+F%3BStoner%2C+G+L&rft.aulast=Jobes&rft.aufirst=D&rft.date=1999-11-01&rft.volume=2&rft.issue=6&rft.spage=350&rft.isbn=&rft.btitle=&rft.title=Journal+of+human+virology&rft.issn=10909508&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-16 N1 - Date created - 2000-05-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [Mental health and work: integrated technical actions between services for preventive hygiene and worksite safety and mental health centers]. TT - Salute mentale e lavoro: azioni tecniche integrate tra i servizi di prevenzione igiene e sicurezza nei luoghi di lavoro e centri di salute mentale. AN - 69445086; 10703191 AB - We analyzed occupational and mental health activities in an occupational health service and in a mental health service using the Method of Organizational Congruences (MOC). No technical actions in either services were dedicated to mental health at work although this is prescribed by the Italian law (833/76) and has a demand among the local shared users identified in this study. We propose integrated technical action for mental health in public health services to address the risk of stress, burnout and mobbing in the workplace. Attention is drawn to the need for further research on health services in the field of organization and mental well-being. JF - La Medicina del lavoro AU - Bosco, M G AU - Salerno, S AU - Valcella, F AD - Azienda Sanitaria Locale Roma B, Servizio di Prevenzione Igiene e Sicurezza nei Luoghi di Lavoro. PY - 1999 SP - 752 EP - 761 VL - 90 IS - 6 SN - 0025-7818, 0025-7818 KW - Index Medicus KW - Workplace -- psychology KW - Risk Factors KW - Humans KW - Burnout, Professional -- prevention & control KW - Occupational Health Services -- organization & administration KW - Occupational Diseases -- prevention & control KW - Male KW - Italy KW - Female KW - Stress, Psychological -- prevention & control KW - Occupational Health KW - Mental Health KW - Community Mental Health Centers -- organization & administration UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69445086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=La+Medicina+del+lavoro&rft.atitle=%5BMental+health+and+work%3A+integrated+technical+actions+between+services+for+preventive+hygiene+and+worksite+safety+and+mental+health+centers%5D.&rft.au=Bosco%2C+M+G%3BSalerno%2C+S%3BValcella%2C+F&rft.aulast=Bosco&rft.aufirst=M&rft.date=1999-11-01&rft.volume=90&rft.issue=6&rft.spage=752&rft.isbn=&rft.btitle=&rft.title=La+Medicina+del+lavoro&rft.issn=00257818&rft_id=info:doi/ LA - Italian DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-22 N1 - Date created - 2000-03-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of p53 and apoptosis in carcinogenesis. AN - 69441901; 10697590 AB - Carcinogenesis is a process that converts normal cells from controllable to uncontrollable growth. Coordinate regulation of the rates of cell proliferation and cell death is an important determinant in maintenance of homeostasis. Loss of control of this balance is central to the development of cancer. This loss may be due to genetic alteration in either growth promoting genes resulting in constitutive activation or negative growth regulating genes such as tumor suppressor genes. Recent advances in studying the molecular mechanisms related to the etiology of cancer have provided further understanding of these pathways. Earlier studies have been primarily concerned with cell proliferation resulting from activation of oncogenes. However, many recent studies have focused on the induction of cell death. The recognition of the importance of apoptosis, a distinct mode of cell death, in maintenance of genomic stability was further prompted by studying the mechanism of the tumor suppressor gene product p53, as well as many other oncogenes and tumor suppressor genes. For example, many oncogenes appear to act as potent inducers of apoptosis through activation of p53 dependent apoptosis pathways. Therefore, one possible mechanism for tumor suppression involves activation of apoptosis pathways in cells at risk of neoplastic transformation. These studies have provided extensive knowledge of the signal transduction pathways in response to genotoxic stress and promoted mechanistic research related to the apoptosis pathways. These studies also provide a perfect explanation that p53 is a key element in maintaining genomic stability and loss of the p53 function is a common event during carcinogenesis. This chapter will mainly focus on the role of apoptosis in carcinogenesis. In particular, I will summarize recent studies related to the mechanisms of p53 and its role in this process. JF - Anticancer research AU - Wang, X W AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. xin-wei-wang@nih.gov PY - 1999 SP - 4759 EP - 4771 VL - 19 IS - 6A SN - 0250-7005, 0250-7005 KW - Index Medicus KW - Neoplasms -- pathology KW - Signal Transduction KW - Neoplasms -- genetics KW - Apoptosis KW - Genes, p53 KW - Cell Transformation, Neoplastic -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69441901?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Role+of+p53+and+apoptosis+in+carcinogenesis.&rft.au=Wang%2C+X+W&rft.aulast=Wang&rft.aufirst=X&rft.date=1999-11-01&rft.volume=19&rft.issue=6A&rft.spage=4759&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-16 N1 - Date created - 2000-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Increased survival in brain metastatic patients treated with stereotactic radiotherapy, omega three fatty acids and bioflavonoids. AN - 69439659; 10697622 AB - Stereotactic radiotherapy represents a method to effectively treat brain metastases with high precision and with high doses. Few acute toxicities are associated with stereotactic radiotherapy, however delayed reactions may occur and after six months, 20% of patients can develop radionecrosis. To avoid this adverse effect, in patients with metastases localized in critical brain areas, a supplementation of Omega three fatty acids and bioflavonoids has been used. At the end of 1997, we initiated a series of retrospective studies to test the efficacy of stereotactic radiotherapy on 405 patients, and the prognostic importance on survival of various variables among which this type of supplementation. From the comparison of various survival curves with the Cox multivariate analysis, it emerged that the patients using this supplementation had a decreased risk ratio and an improvement in survival time. A decreased number of radionecrosis was noted. We suggest their use as radioprotectors. JF - Anticancer research AU - Gramaglia, A AU - Loi, G F AU - Mongioj, V AU - Baronzio, G F AD - National Cancer Institute, Milan, Italy. PY - 1999 SP - 5583 EP - 5586 VL - 19 IS - 6C SN - 0250-7005, 0250-7005 KW - Fatty Acids, Omega-3 KW - 0 KW - Flavonoids KW - Index Medicus KW - Survival Rate KW - Breast Neoplasms -- pathology KW - Combined Modality Therapy KW - Humans KW - Middle Aged KW - Male KW - Female KW - Lung Neoplasms -- pathology KW - Brain Neoplasms -- therapy KW - Brain Neoplasms -- drug therapy KW - Fatty Acids, Omega-3 -- therapeutic use KW - Brain Neoplasms -- radiotherapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Brain Neoplasms -- secondary KW - Flavonoids -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69439659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Increased+survival+in+brain+metastatic+patients+treated+with+stereotactic+radiotherapy%2C+omega+three+fatty+acids+and+bioflavonoids.&rft.au=Gramaglia%2C+A%3BLoi%2C+G+F%3BMongioj%2C+V%3BBaronzio%2C+G+F&rft.aulast=Gramaglia&rft.aufirst=A&rft.date=1999-11-01&rft.volume=19&rft.issue=6C&rft.spage=5583&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-10 N1 - Date created - 2000-03-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The molecular genetics of holoprosencephaly: a model of brain development for the next century. AN - 69358140; 10603005 AB - The recent identification of some of the human holoprosencephaly genes is beginning to elucidate the intricate developmental programs that pattern normal and abnormal brain development. Here we present some of these advances in the context of our present understanding and conclude with some speculations regarding the direction for future investigations. We are living in a tremendously exciting time in medicine with the rapid application of molecular genetic approaches to the understanding of human disease. It is the purpose of this review to stress the underlying principals of our approach at a level that can be readily appreciated by colleagues who themselves are experts in brain anatomy but not necessarily the molecular genetics of brain development. JF - Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery AU - Roessler, E AU - Muenke, M AD - The Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Building 10, 10C101, Bethesda, MD 20892-1852, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 646 EP - 651 VL - 15 IS - 11-12 SN - 0256-7040, 0256-7040 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Molecular Biology KW - Humans KW - Central Nervous System -- embryology KW - Holoprosencephaly -- genetics KW - Holoprosencephaly -- embryology KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69358140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child%27s+nervous+system+%3A+ChNS+%3A+official+journal+of+the+International+Society+for+Pediatric+Neurosurgery&rft.atitle=The+molecular+genetics+of+holoprosencephaly%3A+a+model+of+brain+development+for+the+next+century.&rft.au=Roessler%2C+E%3BMuenke%2C+M&rft.aulast=Roessler&rft.aufirst=E&rft.date=1999-11-01&rft.volume=15&rft.issue=11-12&rft.spage=646&rft.isbn=&rft.btitle=&rft.title=Child%27s+nervous+system+%3A+ChNS+%3A+official+journal+of+the+International+Society+for+Pediatric+Neurosurgery&rft.issn=02567040&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-21 N1 - Date created - 2000-01-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nitric oxide in cyclosporine A-induced hypertension: role of protein kinase C. AN - 69357496; 10604485 AB - Chronic treatment with cyclosporine A (CsA), an immunosuppressive agent, causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and isolated rat aortic rings. Male rats weighing 250 to 300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal injection for 7 days. Cyclosporine A administration produced a 42% increase (P<.001) in mean arterial pressure (MAP), which reached a plateau after 3 days. Conversely, the level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), and 3', 5' cyclic guanosine monophosphate (cGMP), which mediates NO action, decreased by 50% (P<.001) and 35% (P<.001), respectively, in the urine. Thoracic aortic rings from rats treated with CsA, and precontracted with endothelin (10(-9) mol/L), showed a 35% increase (P<.001) in tension, whereas acetylcholine-induced (Ach; 10(-9) mol/L) endothelium-dependent relaxation was inhibited 65% (P<.001) compared with untreated rats. This response was similar to that of aortic rings, denuded of endothelium, from untreated rats in which Ach-induced relaxation was completely abolished (P<.001). Ach-induced formation of both NO2/NO3 and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P<.001) and 65% P<.001), respectively, compared with intact aortic rings. The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (L-Arg; 10 mg/kg/day intraperitoneally), the precursor of NO. There were no changes in MAP and tension in rats treated with L-Arg alone. In addition, in the aorta of rats that were treated intraperitoneally with CsA for 7 days, CsA significantly activated protein kinase C (PKC) translocation and decreased NO2/NO3 production. This suggest that PKC mediates, in part, CsA-induced hypertension. In summary, CsA activates PKC, which inhibits endothelial NO formation, with resulting increases in MAP and tension, and this inhibition can be overcome by L-Arg administration. JF - American journal of hypertension AU - Oriji, G K AU - Keiser, H R AD - Hypertension-Endocrine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1091 EP - 1097 VL - 12 IS - 11 Pt 1 SN - 0895-7061, 0895-7061 KW - Antihypertensive Agents KW - 0 KW - Endothelin Receptor Antagonists KW - Endothelins KW - Immunosuppressive Agents KW - Vasodilator Agents KW - Nitric Oxide KW - 31C4KY9ESH KW - Cyclosporine KW - 83HN0GTJ6D KW - Arginine KW - 94ZLA3W45F KW - Protein Kinase C KW - EC 2.7.11.13 KW - Cyclic GMP KW - H2D2X058MU KW - Acetylcholine KW - N9YNS0M02X KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- metabolism KW - Aorta, Thoracic -- metabolism KW - Cyclic GMP -- urine KW - Acetylcholine -- pharmacology KW - Antihypertensive Agents -- pharmacology KW - Vasodilator Agents -- pharmacology KW - Arginine -- pharmacology KW - Rats KW - Endothelins -- pharmacology KW - Rats, Sprague-Dawley KW - Aorta, Thoracic -- drug effects KW - Endothelium, Vascular -- drug effects KW - Vasodilation -- drug effects KW - Male KW - Hypertension -- chemically induced KW - Immunosuppressive Agents -- toxicity KW - Nitric Oxide -- metabolism KW - Cyclosporine -- toxicity KW - Protein Kinase C -- physiology KW - Hypertension -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69357496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+hypertension&rft.atitle=Nitric+oxide+in+cyclosporine+A-induced+hypertension%3A+role+of+protein+kinase+C.&rft.au=Oriji%2C+G+K%3BKeiser%2C+H+R&rft.aulast=Oriji&rft.aufirst=G&rft.date=1999-11-01&rft.volume=12&rft.issue=11+Pt+1&rft.spage=1091&rft.isbn=&rft.btitle=&rft.title=American+journal+of+hypertension&rft.issn=08957061&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spatial memory improvement by levodopa in parkinsonian MPTP-treated monkeys. AN - 69355963; 10591875 AB - The ameliorative effects of levodopa (L-3,4-dihydroxy-phenylalanine) on the motor impairment in Parkinson's disease patients is well established, but characterization of its effects on the associated cognitive deficits is still incomplete. The present study determined the effect of different doses of levodopa on performance on a test of working memory in MPTP-treated rhesus monkeys, an animal model of Parkinson's disease. Four MPTP-treated monkeys and their age-matched controls with the same experimental history as the MPTP-treated monkeys were tested on a spatial delay response task. Each daily session consisted of five trials at each of seven randomly presented delays (0, 10, 20, 30, 40, 50 and 60 s). Training was continued for 5 days in each of five different conditions. In the first condition, control and MPTP-treated animals performed the task without levodopa. In the second condition, both groups were tested with a dose of 100 mg of levodopa. In the third and fourth conditions, in which the doses of levodopa were increased to 250 and 500 mg, respectively, only the MPTP-treated animals were tested. In the final condition, the MPTP-treated animals where retested without levodopa. Significant improvement was observed at all doses tested (range 100-500 mg). Levodopa can ameliorate memory impairments in this parkinsonian model. JF - Psychopharmacology AU - Fernández-Ruiz, J AU - Doudet, D AU - Aigner, T G AD - Laboratory of Neuropsychology, NIMH, Bethesda, MD 20892-4415, USA. jfr@ln.nimh.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 104 EP - 107 VL - 147 IS - 1 SN - 0033-3158, 0033-3158 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agents KW - Fluorine Radioisotopes KW - fluorodopa F 18 KW - 2C598205QX KW - Levodopa KW - 46627O600J KW - Dihydroxyphenylalanine KW - 63-84-3 KW - Index Medicus KW - Animals KW - Psychomotor Performance -- drug effects KW - Motor Activity -- drug effects KW - Macaca mulatta KW - Male KW - Dihydroxyphenylalanine -- analogs & derivatives KW - Levodopa -- pharmacology KW - Parkinson Disease, Secondary -- psychology KW - Parkinson Disease, Secondary -- chemically induced KW - Dopamine Agents -- toxicity KW - Space Perception -- drug effects KW - Memory -- drug effects KW - MPTP Poisoning -- psychology KW - Antiparkinson Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69355963?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Spatial+memory+improvement+by+levodopa+in+parkinsonian+MPTP-treated+monkeys.&rft.au=Fern%C3%A1ndez-Ruiz%2C+J%3BDoudet%2C+D%3BAigner%2C+T+G&rft.aulast=Fern%C3%A1ndez-Ruiz&rft.aufirst=J&rft.date=1999-11-01&rft.volume=147&rft.issue=1&rft.spage=104&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-24 N1 - Date created - 2000-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered neuroendocrine and behavioral responses to m-chlorophenylpiperazine in 3,4-methylenedioxymethamphetamine (MDMA) users. AN - 69354632; 10591869 AB - (+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse and a brain serotonin neurotoxin in animals. Growing evidence indicates that humans are also susceptible to MDMA's neurotoxic effects, although few functional consequences of MDMA-induced 5-HT damage have been identified. The present study sought to determine whether possible differences between MDMA users and control subjects could be unmasked by utilizing a pharmacological challenge with the mixed 5-HT agonist, meta-chlorophenylpiperazine (m-CPP). It was postulated that 5-HT neurotoxicity in MDMA users would be associated with altered 5-HT responsivity, exemplified by altered physiological and behavioral responses to m-CPP. Twenty-five MDMA users who had not taken MDMA for at least 3 weeks and 25 controls received intravenous placebo (normal saline) and m-CPP (0.08 mg/kg) in a fixed order, single blind design. Repeated measures of mood, physical symptoms, and blood samples for neuroendocrine analyses were collected during the 90 min after each infusion. MDMA users reported more positive and fewer negative emotions and physical symptoms following m-CPP than controls, and were significantly less likely to report an m-CPP-induced panic attack. Male MDMA users had diminished cortisol and prolactin responses to m-CPP. The present data indicate that MDMA users have alterations in 5-HT neuronal function, possibly as a consequence of MDMA-induced brain serotonin neural injury. JF - Psychopharmacology AU - McCann, U D AU - Eligulashvili, V AU - Mertl, M AU - Murphy, D L AU - Ricaurte, G A AD - Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892-1272, USA. umccann@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 56 EP - 65 VL - 147 IS - 1 SN - 0033-3158, 0033-3158 KW - Hallucinogens KW - 0 KW - Piperazines KW - Serotonin Receptor Agonists KW - Serotonin KW - 333DO1RDJY KW - Prolactin KW - 9002-62-4 KW - N-Methyl-3,4-methylenedioxyamphetamine KW - KE1SEN21RM KW - 1-(3-chlorophenyl)piperazine KW - REY0CNO998 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Prolactin -- blood KW - Anxiety -- psychology KW - Affect -- drug effects KW - Single-Blind Method KW - Humans KW - Adult KW - Male KW - Hydrocortisone -- blood KW - Female KW - Serotonin Receptor Agonists -- blood KW - Behavior -- drug effects KW - N-Methyl-3,4-methylenedioxyamphetamine -- adverse effects KW - Serotonin -- physiology KW - Neurosecretory Systems -- drug effects KW - Hallucinogens -- adverse effects KW - Piperazines -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69354632?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Altered+neuroendocrine+and+behavioral+responses+to+m-chlorophenylpiperazine+in+3%2C4-methylenedioxymethamphetamine+%28MDMA%29+users.&rft.au=McCann%2C+U+D%3BEligulashvili%2C+V%3BMertl%2C+M%3BMurphy%2C+D+L%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1999-11-01&rft.volume=147&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-24 N1 - Date created - 2000-01-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Temperature and air pollution as risk factors for heat stroke in Tokyo, July and August 1980-1995. AN - 69354612; 10544159 AB - Heat stroke is associated with prolonged exposures to high air temperatures that usually occur in the summer months of July and August in Tokyo, Japan. Also during July and August, residents of Tokyo are often exposed simultaneously to high concentrations of air pollutants. To assess the impacts of these combined exposures, daily numbers of heat stroke emergency transport cases/million residents for Tokyo were stratified by gender and three groups: 0-14, 15-64; and > 65 years of age, for the months of July and August in 1980-1995. A regression model was constructed using daily maximum temperature (Tmax) and daily average concentrations of NO2 and O3 as model covariates. Classification indices were added to make it possible to compare the expected number of heat stroke cases by age and gender. Lag times of 1-4 days in Tmax and air quality covariates and terms to account for interactions between pairs of model covariates were also included as additional risk factors. Generalized linear models (GLMs), assuming a Poisson error structure for heat stroke emergency transport cases, were used to determine which covariates were significant risk factors for heat stroke for the three age groups of males and females. Same-day Tmax and concentrations of NO2 were the most significant risk factors for heat stroke in all age groups of males and females. The number of heat stroke emergency transport cases/million residents was greater in males than in females in the same age groups. The smallest number of heat stroke emergency transport cases/million residents occurred for females 0-14 years of age and the greatest number of heat stroke emergency transport cases/million residents occurred for males > 65 years of age. JF - Environmental health perspectives AU - Piver, W T AU - Ando, M AU - Ye, F AU - Portier, C J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. piver@niehs.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 911 EP - 916 VL - 107 IS - 11 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Regression Analysis KW - Age Factors KW - Sex Factors KW - Tokyo KW - Humans KW - Infant, Newborn KW - Aged KW - Child KW - Emergency Service, Hospital -- utilization KW - Risk Assessment KW - Child, Preschool KW - Infant KW - Adult KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Air Pollution -- adverse effects KW - Heat Stroke -- etiology KW - Temperature UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69354612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Exploring+the+conformational+properties+of+the+sequence+space+between+two+proteins+with+different+folds%3A+an+experimental+study.&rft.au=Blanco%2C+F+J%3BAngrand%2C+I%3BSerrano%2C+L&rft.aulast=Blanco&rft.aufirst=F&rft.date=1999-01-15&rft.volume=285&rft.issue=2&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am Rev Respir Dis. 1980 Jan;121(1):3-10 [7352711] JAMA. 1982 Jun 25;247(24):3327-31 [7087075] JAMA. 1982 Jun 25;247(24):3332-6 [7087076] Environ Health Perspect. 1983 Oct;52:115-23 [6653513] Am Rev Respir Dis. 1984 Mar;129(3):366-74 [6703495] Am J Epidemiol. 1986 Feb;123(2):250-60 [3946374] Ann Intern Med. 1998 Aug 1;129(3):173-81 [9696724] Am Rev Respir Dis. 1989 Mar;139(3):587-94 [2923355] Am J Epidemiol. 1991 Jul 15;134(2):204-19 [1862804] Am J Epidemiol. 1993 May 15;137(10):1136-47 [8317443] Chest. 1993 Nov;104(5):1498-502 [8222814] Biometrics. 1994 Mar;50(1):270-8 [8086610] Environ Health Perspect. 1997 Jul;105(7):726-33 [9294719] Biochem J. 1986 Dec 1;240(2):313-24 [3545184] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Real-time measurements of dark substrate catalysis. AN - 69351176; 10595550 AB - We have developed a novel procedure to monitor the real-time cleavage of natural unmodified peptides (dark substrates). In the competition-based assay, the initial cleavage rate of a fluorogenic peptide substrate is measured in the presence of a second substrate that is not required to exhibit any optical property change upon cleavage. Using a unique experimental design and steady-state enzyme kinetics for a two-substrate system, we were able to determine both Km and k(cat) values for cleavage of the dark substrate. The method was applied to HIV-1 protease and to the V82F/I84V drug resistant mutant enzyme. Using two different substrates, we showed that the kinetic parameters derived from the competition assay are in good agreement with those determined independently using standard direct assay. This method can be applied to other enzyme systems as long as they have one substrate for which catalysis can be conveniently monitored in real time. JF - Protein science : a publication of the Protein Society AU - Xie, D AU - Suvorov, L AU - Erickson, J W AU - Gulnik, A S AD - Structural Biochemistry Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 2460 EP - 2464 VL - 8 IS - 11 SN - 0961-8368, 0961-8368 KW - Enzymes KW - 0 KW - Oligopeptides KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Regression Analysis KW - Kinetics KW - Oligopeptides -- chemistry KW - Oligopeptides -- metabolism KW - Amino Acid Sequence KW - Substrate Specificity KW - Amino Acid Substitution KW - Models, Theoretical KW - Catalysis KW - Enzymes -- metabolism KW - HIV Protease -- metabolism KW - HIV Protease -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69351176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Real-time+measurements+of+dark+substrate+catalysis.&rft.au=Xie%2C+D%3BSuvorov%2C+L%3BErickson%2C+J+W%3BGulnik%2C+A+S&rft.aulast=Xie&rft.aufirst=D&rft.date=1999-11-01&rft.volume=8&rft.issue=11&rft.spage=2460&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-07 N1 - Date created - 2000-01-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1990 Feb 23;247(4945):954-8 [2106161] Methods Enzymol. 1979;63:486-500 [502867] J Biol Chem. 1992 May 15;267(14):9481-90 [1315755] Biochemistry. 1993 Apr 27;32(16):4344-8 [8476864] Methods Enzymol. 1994;241:127-56 [7854175] Methods Enzymol. 1994;241:254-78 [7854181] Methods Enzymol. 1994;241:279-301 [7854182] Methods Enzymol. 1994;241:70-86 [7854193] Biochemistry. 1995 Jul 25;34(29):9282-7 [7626598] Anal Biochem. 1995 May 1;227(1):242-5 [7668386] J Virol. 1996 Jun;70(6):3763-9 [8648711] J Biol Chem. 1996 Dec 13;271(50):31957-63 [8943242] J Biol Chem. 1996 Dec 27;271(52):33231-5 [8969180] Biochim Biophys Acta. 1997 Apr 25;1339(1):113-25 [9165106] J Virol. 1997 Sep;71(9):6662-70 [9261388] Biochemistry. 1997 Oct 7;36(40):12364-70 [9315877] Biochemistry. 1991 Aug 27;30(34):8441-53 [1883830] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Leukaemia disease genes: large-scale cloning and pathway predictions. AN - 69339834; 10610183 AB - Retroviral insertional mutagenesis in BXH2 and AKXD recombinant inbred mice induces a high incidence of myeloid or B- and T-cell leukaemia and the proviral integration sites in the leukaemias provide powerful genetic tags for disease gene identification. Some of the disease genes identified by proviral tagging are also associated with human disease, validating this approach for human disease gene identification. Although many leukaemia disease genes have been identified over the years, many more remain to be cloned. Here we describe an inverse PCR (IPCR) method for proviral tagging that makes use of automated DNA sequencing and the genetic tools provided by the Mouse Genome Project, which increases the throughput for disease gene identification. We also use this IPCR method to clone and analyse more than 400 proviral integration sites from AKXD and BXH2 leukaemias and, in the process, identify more than 90 candidate disease genes. Some of these genes function in pathways already implicated in leukaemia, whereas others are likely to define new disease pathways. Our studies underscore the power of the mouse as a tool for gene discovery and functional genomics. JF - Nature genetics AU - Li, J AU - Shen, H AU - Himmel, K L AU - Dupuy, A J AU - Largaespada, D A AU - Nakamura, T AU - Shaughnessy, J D AU - Jenkins, N A AU - Copeland, N G AD - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 348 EP - 353 VL - 23 IS - 3 SN - 1061-4036, 1061-4036 KW - Index Medicus KW - Sensitivity and Specificity KW - Animals KW - Reproducibility of Results KW - Sequence Homology, Nucleic Acid KW - Humans KW - Mice KW - Chromosomes -- genetics KW - Genome KW - Mice, Inbred Strains KW - Tumor Cells, Cultured KW - Lymphoma -- genetics KW - Physical Chromosome Mapping KW - Polymerase Chain Reaction -- methods KW - Proviruses -- genetics KW - Retroviridae -- genetics KW - Expressed Sequence Tags KW - Mutagenesis, Insertional KW - Oncogenes -- genetics KW - Signal Transduction -- genetics KW - Cloning, Molecular -- methods KW - Leukemia, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69339834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Leukaemia+disease+genes%3A+large-scale+cloning+and+pathway+predictions.&rft.au=Li%2C+J%3BShen%2C+H%3BHimmel%2C+K+L%3BDupuy%2C+A+J%3BLargaespada%2C+D+A%3BNakamura%2C+T%3BShaughnessy%2C+J+D%3BJenkins%2C+N+A%3BCopeland%2C+N+G&rft.aulast=Li&rft.aufirst=J&rft.date=1999-11-01&rft.volume=23&rft.issue=3&rft.spage=348&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-07 N1 - Date created - 1999-12-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Genet. 1999 Nov;23(3):253-4 [10545932] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Allelic loss in esophageal squamous cell carcinoma patients with and without family history of upper gastrointestinal tract cancer. AN - 69338352; 10589761 AB - Chromosomal regions with frequent allelic loss may point to major susceptibility genes that will assist in understanding molecular events involved in esophageal carcinogenesis. Esophageal squamous cell carcinoma samples and blood from 46 patients, including 23 patients with and 23 patients without a family history of upper gastrointestinal cancer, were screened using laser microdissected DNA and tested for loss of heterozygosity (LOH) at 18 marker loci representing 14 chromosomal regions (on 2q, 3p, 4p, 4p, 5q, 6q, 8p, 9p, 9q, 11p, 13q, 14q, 15q, and 17p) identified in an earlier genome-wide scan to have frequent LOH. Clinical/pathological and lifestyle risk factor data were also collected. For all 46 tumors combined, the lowest frequency LOH for any of the 18 markers was 37%, and 8 markers showed LOH in > or =75% of informative tumors. One marker (D13S894 on 13q) showed greater LOH in patients with a positive family history (93% versus 50%; P = 0.04), whereas two markers (D6S1027 on 6q and D9S910 on 9q) had significantly more LOH in patients with metastasis, and one marker (D4S2361 on 4p) showed significantly higher LOH in patients with a lower pathological tumor grade. No relation was seen between LOH and lifestyle risk factors. This study confirms the previously observed high frequency LOH for these 14 chromosomal regions, including a locus on 13q where LOH is more common in patients with a family history of upper gastrointestinal cancer than in those without such history, suggesting that a gene in this area may be involved in genetic susceptibility to esophageal cancer. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Hu, N AU - Roth, M J AU - Emmert-Buck, M R AU - Tang, Z Z AU - Polymeropolous, M AU - Wang, Q H AU - Goldstein, A M AU - Han, X Y AU - Dawsey, S M AU - Ding, T AU - Giffen, C AU - Taylor, P R AD - National Cancer Institute, Bethesda, Maryland 20892-7058, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 3476 EP - 3482 VL - 5 IS - 11 SN - 1078-0432, 1078-0432 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Lymphatic Metastasis KW - Humans KW - Aged KW - Life Style KW - Polymerase Chain Reaction KW - Microsatellite Repeats KW - Risk Factors KW - China -- epidemiology KW - Adult KW - Family KW - Middle Aged KW - Genetic Predisposition to Disease KW - Female KW - Male KW - Gastrointestinal Neoplasms -- genetics KW - Loss of Heterozygosity KW - Carcinoma, Squamous Cell -- epidemiology KW - Carcinoma, Squamous Cell -- pathology KW - Chromosomes, Human KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - Chromosome Mapping KW - Esophageal Neoplasms -- pathology KW - Esophageal Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69338352?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Allelic+loss+in+esophageal+squamous+cell+carcinoma+patients+with+and+without+family+history+of+upper+gastrointestinal+tract+cancer.&rft.au=Hu%2C+N%3BRoth%2C+M+J%3BEmmert-Buck%2C+M+R%3BTang%2C+Z+Z%3BPolymeropolous%2C+M%3BWang%2C+Q+H%3BGoldstein%2C+A+M%3BHan%2C+X+Y%3BDawsey%2C+S+M%3BDing%2C+T%3BGiffen%2C+C%3BTaylor%2C+P+R&rft.aulast=Hu&rft.aufirst=N&rft.date=1999-11-01&rft.volume=5&rft.issue=11&rft.spage=3476&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phase I and imaging trial of a monoclonal antibody directed against gastrin-releasing peptide in patients with lung cancer. AN - 69336862; 10589749 AB - Small cell lung cancer (SCLC) cells express and secrete bombesin-like peptides (BLP) that can activate specific receptors that stimulate the growth of these cells. A murine monoclonal antibody, 2A11, which binds to the BLP, gastrin-releasing peptide with high affinity, has been reported to decrease the growth of SCLC cells in vitro and in athymic nude mice. A Phase I trial in lung cancer patients was performed using multiple doses of 2A11. Thirteen patients with lung cancer received 12 doses of 2A11 antibody three times a week for 4 weeks at one of four dose levels. Serum samples were obtained prior to initiation and before each dose of 2A11 antibody therapy for measurement of 2A11 antibody levels and determination of serum human anti-mouse antibody levels. A pilot imaging evaluation using 111In conjugated 2A11 monoclonal antibody was also performed in the same patients to aid in the study of pharmacokinetics and biodistribution. No toxic reactions were observed, and none of the patients developed detectable human antimouse antibody; however, no objective antitumor responses were observed. The mean trough serum 2A11 levels in patients increased with increasing dose level: 0.26+/-0.2 microg/ml, 6.7+/-6 microg/ml, 71.5+/-60 microg/ml, 248+/-184 microg/ml for dose levels 1 mg/m2, 10 mg/m2, 100 mg/m2, and 250 mg/m2, respectively. At each dose level, sustained detectable serum levels of the monoclonal antibody were achieved. Tumor uptake was noted in 11 of 12 patients who were injected with 111In conjugated 2A11. Because no dose-limiting clinical toxicity was observed, a mathematical model was used to define the recommended Phase II dose of 250 mg/m2. This trial established that repeated doses of monoclonal antibody 2A11 could be given safely to patients, and sustained levels could be achieved for a 4-week schedule. Further evaluation of the antitumor effects of 2A11 is warranted. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Chaudhry, A AU - Carrasquillo, J A AU - Avis, I L AU - Shuke, N AU - Reynolds, J C AU - Bartholomew, R AU - Larson, S M AU - Cuttitta, F AU - Johnson, B E AU - Mulshine, J L AD - Intervention Section, Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-1906, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 3385 EP - 3393 VL - 5 IS - 11 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Immunoglobulin G KW - Indium Radioisotopes KW - Gastrin-Releasing Peptide KW - 80043-53-4 KW - Index Medicus KW - Animals KW - Immunoglobulin G -- adverse effects KW - Humans KW - Mice KW - Male KW - Female KW - Carcinoma, Non-Small-Cell Lung -- diagnostic imaging KW - Antibodies, Monoclonal -- pharmacokinetics KW - Radioimmunodetection KW - Indium Radioisotopes -- pharmacokinetics KW - Carcinoma, Small Cell -- diagnostic imaging KW - Antibodies, Monoclonal -- adverse effects KW - Gastrin-Releasing Peptide -- immunology KW - Lung Neoplasms -- diagnostic imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69336862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Phase+I+and+imaging+trial+of+a+monoclonal+antibody+directed+against+gastrin-releasing+peptide+in+patients+with+lung+cancer.&rft.au=Chaudhry%2C+A%3BCarrasquillo%2C+J+A%3BAvis%2C+I+L%3BShuke%2C+N%3BReynolds%2C+J+C%3BBartholomew%2C+R%3BLarson%2C+S+M%3BCuttitta%2C+F%3BJohnson%2C+B+E%3BMulshine%2C+J+L&rft.aulast=Chaudhry&rft.aufirst=A&rft.date=1999-11-01&rft.volume=5&rft.issue=11&rft.spage=3385&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Detection of azide in forensic samples by capillary electrophoresis. AN - 69333716; 10582374 AB - Azide salts are highly toxic compounds that have been difficult to detect in forensic samples. Here, anion analysis by capillary electrophoresis with indirect spectrophotometric detection was applied to detect azide in forensic specimens from two suicide victims. Gastric specimens from the victims were shown to have high azide concentrations; azide represented one of the major anionic components and no corresponding component occurred in normal gastric juice. Samples of blood and bile had low concentrations of azide near the limits of detection. The method described for azide analysis used simple steps for sample preparation and analysis time was less than 10 min per sample. It offers a simple and reliable method for detecting azide in biological fluids. JF - Journal of forensic sciences AU - Hortin, G L AU - Dey, S K AU - Hall, M AU - Robinson, C A AD - National Institutes of Health, Clinical Pathology Department, Bethesda, MD, USA. ghortin@cc.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1310 EP - 1313 VL - 44 IS - 6 SN - 0022-1198, 0022-1198 KW - Azides KW - 0 KW - Index Medicus KW - Sensitivity and Specificity KW - Humans KW - Toxicology -- methods KW - Spectrophotometry KW - Azides -- analysis KW - Forensic Medicine -- methods KW - Azides -- poisoning KW - Electrophoresis, Capillary -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69333716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+forensic+sciences&rft.atitle=Detection+of+azide+in+forensic+samples+by+capillary+electrophoresis.&rft.au=Hortin%2C+G+L%3BDey%2C+S+K%3BHall%2C+M%3BRobinson%2C+C+A&rft.aulast=Hortin&rft.aufirst=G&rft.date=1999-11-01&rft.volume=44&rft.issue=6&rft.spage=1310&rft.isbn=&rft.btitle=&rft.title=Journal+of+forensic+sciences&rft.issn=00221198&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-16 N1 - Date created - 1999-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular remission of chronic myeloid leukaemia following a non-myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft-versus-leukaemia effect. AN - 69332016; 10583233 AB - Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and fludarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30-50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor). These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versus-leukaemia effect. JF - British journal of haematology AU - Childs, R AU - Epperson, D AU - Bahceci, E AU - Clave, E AU - Barrett, J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1652, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 396 EP - 400 VL - 107 IS - 2 SN - 0007-1048, 0007-1048 KW - Granulocyte Colony-Stimulating Factor KW - 143011-72-7 KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Cyclophosphamide -- administration & dosage KW - Vidarabine -- analogs & derivatives KW - Granulocyte Colony-Stimulating Factor -- therapeutic use KW - Humans KW - Adult KW - Middle Aged KW - Vidarabine -- administration & dosage KW - Reverse Transcriptase Polymerase Chain Reaction KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Male KW - Graft vs Leukemia Effect -- drug effects KW - Female KW - Remission Induction KW - Hematopoietic Stem Cell Transplantation KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69332016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+haematology&rft.atitle=Molecular+remission+of+chronic+myeloid+leukaemia+following+a+non-myeloablative+allogeneic+peripheral+blood+stem+cell+transplant%3A+in+vivo+and+in+vitro+evidence+for+a+graft-versus-leukaemia+effect.&rft.au=Childs%2C+R%3BEpperson%2C+D%3BBahceci%2C+E%3BClave%2C+E%3BBarrett%2C+J&rft.aulast=Childs&rft.aufirst=R&rft.date=1999-11-01&rft.volume=107&rft.issue=2&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=British+journal+of+haematology&rft.issn=00071048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of 4-nonylphenol in rats: a multigeneration reproduction study. AN - 69283702; 10568701 AB - The alkylphenol breakdown products of alkylphenol ethoxylates have been shown in in vitro studies to be weakly estrogenic, but few in vivo data address this issue in mammals. Because estrogens have been found to be most potent during developmental/perinatal exposures, this study maximized developmental exposure to nonylphenol (NP) by treating 3.5 generations of Sprague-Dawley rats to NP in diet at 200, 650, and 2000 ppm to determine the range and severity of any toxicity. Dose rate was higher for younger rats; calculated dose ranges were 9-35, 30-100, and 100-350 mg/kg/d for the low (200NP), middle (650NP), and high (2000NP) dose groups, respectively. There were adult (F0, F1, F2) and postnatal day (pnd) 21 (F1, F2, F3) necropsies; the oldest F3 rats were killed on pnd 55-58. Body weight gain was reduced by 8-10% in the 650NP and 2000NP groups. Vaginal opening was accelerated by approximately 2 days (650NP) and approximately 6 days (2000NP) in F1, F2, and F3 generations. Uterine weights at pnd 21 were increased in 650NP (14%) and 2000NP (50%) F1 females, but not in other generations. Testis descent, anogenital distance, and preputial separation were not consistently changed. No consistent changes were seen in pup number, weight or viability, litter indices, or other functional reproductive measures. Relative ovary weight in F2 adults was decreased at 650NP and 2000NP by 12%; relative ovary was unchanged in other generations. Follicle counts were unchanged in F2 adults. Sperm indices, including CASA measures, were unchanged in F0 and F1 males. In F2 rats, epididymal sperm density was reduced by 8% and 13% at 650NP and 2000NP, respectively. Testicular spermatid count was reduced by 13% in 2000NP F2 males; testis and epididymis weights were unchanged. Erosion of gastric and duodenal mucosa was monitored grossly and microscopically, and never found. Kidney weights were increased in 650NP and 2000NP males, and renal medullary tubular dilatation and cyst formation were noted in all generations of males, and often at the lowest dose tested. These data show that NP had limited effects on the reproductive system in the presence of measurable nephrotoxicity. The F2 sperm effects are either statistical/biological "noise," or imply heretofore unknown pharmacokinetics or toxicodynamics. These sperm data should be interpreted cautiously until the findings are repeated. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chapin, R E AU - Delaney, J AU - Wang, Y AU - Lanning, L AU - Davis, B AU - Collins, B AU - Mintz, N AU - Wolfe, G AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chapin@niehs.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 80 EP - 91 VL - 52 IS - 1 SN - 1096-6080, 1096-6080 KW - Phenols KW - 0 KW - 4-nonylphenol KW - I03GBV4WEL KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Diet KW - Male KW - Female KW - Pregnancy KW - Reproduction -- drug effects KW - Phenols -- toxicity KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69283702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=The+effects+of+4-nonylphenol+in+rats%3A+a+multigeneration+reproduction+study.&rft.au=Chapin%2C+R+E%3BDelaney%2C+J%3BWang%2C+Y%3BLanning%2C+L%3BDavis%2C+B%3BCollins%2C+B%3BMintz%2C+N%3BWolfe%2C+G&rft.aulast=Chapin&rft.aufirst=R&rft.date=1999-11-01&rft.volume=52&rft.issue=1&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of vitamin intervention on the relationship between GSTM1, smoking, and lung cancer risk among male smokers. AN - 69283015; 10566550 AB - The GSTM1 (glutathione S-transferase mu-1) null genotype is suspected of increasing an individual's susceptibility to tobacco smoke carcinogens because of impaired carcinogen detoxification. We were interested in whether there were differences in lung cancer susceptibility to smoking within the GSTM1 genotypes and the impact of antioxidant supplementation on this. For this purpose, we conducted a nested lung cancer case-control study and evaluated the role of GSTM1 within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. GSTM1 genotype status was determined for 319 cases and 333 controls using a PCR-based approach. GSTM1 was evaluated as an independent risk factor and as an effect modifier of smoking using logistic regression analyses. The GSTM1 null genotype itself was unrelated to risk of lung cancer, odds ratio (OR) = 1.09 and 95% confidence interval (CI), 0.79-1.50, but it may have modified the effect of smoking. There was a suggestion for a stronger association between years of smoking and lung cancer among the GSTM1 null genotype, but the differences between GSTM1 null and present genotypes were not statistically significant (P = 0.12). Furthermore, the smoking association was strongest among those with the GSTM1 null genotype not receiving alpha-tocopherol supplementation, whereas among those receiving alpha-tocopherol, there was no modification by GSTM1 on the association between smoking duration and lung cancer risk. Beta-carotene supplementation did not modify the relationship between GSTM1, smoking years, and lung cancer risk. In conclusion, GSTM1 is not associated with lung cancer risk in male smokers but may confer a higher susceptibility to cumulative tobacco exposure. This association may be attenuated by alpha-tocopherol but not by beta-carotene supplementation. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Woodson, K AU - Stewart, C AU - Barrett, M AU - Bhat, N K AU - Virtamo, J AU - Taylor, P R AU - Albanes, D AD - Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892-7058, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 965 EP - 970 VL - 8 IS - 11 SN - 1055-9965, 1055-9965 KW - Antioxidants KW - 0 KW - beta Carotene KW - 01YAE03M7J KW - Vitamin E KW - 1406-18-4 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Odds Ratio KW - Humans KW - Aged KW - Multivariate Analysis KW - Age Distribution KW - Genotype KW - Polymerase Chain Reaction KW - Logistic Models KW - Risk Factors KW - Adult KW - Cohort Studies KW - Sampling Studies KW - Case-Control Studies KW - Confidence Intervals KW - Incidence KW - Middle Aged KW - Finland -- epidemiology KW - Male KW - Antioxidants -- administration & dosage KW - beta Carotene -- administration & dosage KW - Lung Neoplasms -- epidemiology KW - Lung Neoplasms -- drug therapy KW - Smoking -- adverse effects KW - Lung Neoplasms -- genetics KW - Glutathione Transferase -- genetics KW - Vitamin E -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69283015?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Effect+of+vitamin+intervention+on+the+relationship+between+GSTM1%2C+smoking%2C+and+lung+cancer+risk+among+male+smokers.&rft.au=Woodson%2C+K%3BStewart%2C+C%3BBarrett%2C+M%3BBhat%2C+N+K%3BVirtamo%2C+J%3BTaylor%2C+P+R%3BAlbanes%2C+D&rft.aulast=Woodson&rft.aufirst=K&rft.date=1999-11-01&rft.volume=8&rft.issue=11&rft.spage=965&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-13 N1 - Date created - 2000-01-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergy between the herpes simplex virus tk/ganciclovir prodrug suicide system and the topoisomerase I inhibitor topotecan. AN - 69273717; 10566896 AB - An established principle of antineoplastic chemotherapy is that multidrug regimens are generally superior to single-agent therapy. This prompted us to elucidate whether the topoisomerase inhibitor topotecan (TPT) could enhance the efficacy of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system for the treatment of cancer. We assessed the interaction between these two treatments in murine MC38 and human HT-29 colon carcinoma cell lines that were genetically modified to constitutively express HSV-tk, sensitizing them to GCV. Synergistic cell killing was observed in a clonogenic assay over most of the cytotoxic dose range by the median-effect principle of Chou and Talalay (Adv. Enzyme Regul. 1984; 22:27-55). Subcutaneous tumor models, using the same cell lines in C57BL/6 and athymic nude mice, respectively, demonstrated that the combination of GCV and TPT resulted in statistically significant enhanced survival relative to single-agent treatment. In addition, nude mice bearing HT-29 tumor xenografts were treated with an Ad5 E1b Mr 55,000 attenuated replication-competent adenovirus expressing HSV-tk (Ad.TK(RC)) either alone or in combination with GCV and/or TPT. These experiments demonstrated that Ad.TK(RC) followed by GCV and TPT was more efficacious than any other treatment tested. Our results suggest that for antineoplastic therapy, molecular chemotherapy based on the HSV-tk/GCV system combined with traditional chemotherapy is a logical and practical future direction to pursue. Suicide gene therapy is the approach whereby genetically altering a cell makes it susceptible to an otherwise relatively nontoxic prodrug. By this approach it is possible to achieve relatively high concentrations of the toxic metabolites in the transduced cells while maintaining low systemic levels of the active drug. The most often used metabolic suicide gene transfer system is the HSV-tk/GCV paradigm, which is currently being used in cancer therapy or as a safety modality. The low response rate observed in the early clinical HSV-tk cancer trials may be due to failure in achieving adequate transduction efficiency and/or prodrug concentration within the tumor. The combination of such suicide gene prodrug systems with adjunctive drugs resulting in synergistic cytotoxicity might improve the clinical utility of this approach. JF - Human gene therapy AU - Wildner, O AU - Blaese, R M AU - Morris, J C AD - Clinical Gene Therapy Branch/National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1851, USA. owildner@nhgri.nih.gov Y1 - 1999/11/01/ PY - 1999 DA - 1999 Nov 01 SP - 2679 EP - 2687 VL - 10 IS - 16 SN - 1043-0342, 1043-0342 KW - Antiviral Agents KW - 0 KW - Enzyme Inhibitors KW - Prodrugs KW - Topoisomerase I Inhibitors KW - Topotecan KW - 7M7YKX2N15 KW - Thymidine Kinase KW - EC 2.7.1.21 KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - Animals KW - Enzyme Inhibitors -- administration & dosage KW - Humans KW - Mice, Nude KW - Mice KW - Mice, Inbred BALB C KW - Prodrugs -- administration & dosage KW - Adenoviridae -- genetics KW - Tumor Cells, Cultured KW - Survival Rate KW - Antiviral Agents -- pharmacology KW - Carcinoma -- drug therapy KW - Colonic Neoplasms -- mortality KW - Colonic Neoplasms -- drug therapy KW - Mice, Inbred C57BL KW - Carcinogenicity Tests KW - Transplantation, Heterologous KW - Carcinoma -- mortality KW - Drug Synergism KW - Female KW - Ganciclovir -- administration & dosage KW - Thymidine Kinase -- pharmacology KW - Topotecan -- administration & dosage KW - Simplexvirus -- enzymology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Thymidine Kinase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69273717?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+gene+therapy&rft.atitle=Synergy+between+the+herpes+simplex+virus+tk%2Fganciclovir+prodrug+suicide+system+and+the+topoisomerase+I+inhibitor+topotecan.&rft.au=Wildner%2C+O%3BBlaese%2C+R+M%3BMorris%2C+J+C&rft.aulast=Wildner&rft.aufirst=O&rft.date=1999-11-01&rft.volume=10&rft.issue=16&rft.spage=2679&rft.isbn=&rft.btitle=&rft.title=Human+gene+therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-16 N1 - Date created - 1999-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The ATPase domain but not the acidic region of Cockayne syndrome group B gene product is essential for DNA repair. AN - 69273373; 10564257 AB - Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA and CSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, the CSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways. JF - Molecular biology of the cell AU - Brosh, R M AU - Balajee, A S AU - Selzer, R R AU - Sunesen, M AU - Proietti De Santis, L AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 3583 EP - 3594 VL - 10 IS - 11 SN - 1059-1524, 1059-1524 KW - Pyrimidine Dimers KW - 0 KW - RNA, Messenger KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - Tetrahydrofolate Dehydrogenase KW - EC 1.5.1.3 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - ERCC6 protein, human KW - EC 3.6.4.12 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Clone Cells -- radiation effects KW - DNA Damage KW - Humans KW - Amino Acid Sequence KW - Cell Survival KW - Mutagenesis, Site-Directed KW - 4-Nitroquinoline-1-oxide -- pharmacology KW - Pyrimidine Dimers -- genetics KW - RNA, Messenger -- metabolism KW - Transfection KW - Cockayne Syndrome -- genetics KW - Molecular Sequence Data KW - Cell Line KW - Tetrahydrofolate Dehydrogenase -- genetics KW - Cricetinae KW - DNA Repair -- genetics KW - DNA Helicases -- chemistry KW - DNA Helicases -- genetics KW - Adenosine Triphosphatases -- chemistry KW - Adenosine Triphosphatases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69273373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+biology+of+the+cell&rft.atitle=The+ATPase+domain+but+not+the+acidic+region+of+Cockayne+syndrome+group+B+gene+product+is+essential+for+DNA+repair.&rft.au=Brosh%2C+R+M%3BBalajee%2C+A+S%3BSelzer%2C+R+R%3BSunesen%2C+M%3BProietti+De+Santis%2C+L%3BBohr%2C+V+A&rft.aulast=Brosh&rft.aufirst=R&rft.date=1999-11-01&rft.volume=10&rft.issue=11&rft.spage=3583&rft.isbn=&rft.btitle=&rft.title=Molecular+biology+of+the+cell&rft.issn=10591524&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-09 N1 - Date created - 1999-12-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Am J Hum Genet. 1998 Jan;62(1):77-85 [9443879] Nucleic Acids Res. 1996 Sep 1;24(17):3317-22 [8811084] J Biol Chem. 1998 May 8;273(19):11844-51 [9565609] J Biol Chem. 1998 May 29;273(22):13599-604 [9593697] J Biol Chem. 1998 Oct 23;273(43):27794-9 [9774388] EMBO J. 1999 Apr 15;18(8):2254-64 [10205178] Biochemistry. 1999 May 11;38(19):6204-12 [10320349] Adv Biol Med Phys. 1968;12:283-98 [4879501] Mutat Res. 1972 May;15(1):98-100 [5025205] J Mol Biol. 1975 Feb 25;92(2):341-56 [806692] Mutat Res. 1979 Jan;59(1):49-60 [431551] Cancer Res. 1979 Oct;39(10):4237-41 [157803] Somatic Cell Genet. 1981 Jul;7(4):445-55 [7280930] Cancer Res. 1982 Apr;42(4):1473-8 [6174225] Mutat Res. 1982 Dec;106(2):347-56 [6185841] Cancer Res. 1985 Feb;45(2):520-5 [3917848] Cell. 1985 Feb;40(2):359-69 [3838150] Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82 [3466163] Cell. 1987 Mar 13;48(5):847-53 [3028647] Proc Natl Acad Sci U S A. 1987 Mar;84(6):1472-6 [3470736] Biochem Biophys Res Commun. 1987 Dec 31;149(3):1141-8 [3122745] Nucleic Acids Res. 1988 Feb 11;16(3):1215 [3344216] Nature. 1988 Jun 16;333(6174):635-40 [3287180] Nature. 1988 Oct 20;335(6192):683-9 [3050531] Genes Dev. 1988 Nov;2(11):1476-85 [2850263] Nucleic Acids Res. 1989 Feb 11;17(3):1197-214 [2922262] Photochem Photobiol. 1989 Jun;49(6):805-19 [2672059] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4707-11 [2352945] Nature. 1990 Jun 28;345(6278):783-6 [2193231] Mol Cell Biol. 1990 Nov;10(11):5806-13 [2172786] Methods Enzymol. 1991;204:125-39 [1943776] EMBO J. 1992 Jul;11(7):2643-54 [1378397] Cancer Res. 1992 Aug 1;52(15):4183-9 [1638532] Cell. 1992 Dec 11;71(6):939-53 [1339317] J Biol Chem. 1993 Jan 25;268(3):1650-7 [8420940] Genes Dev. 1993 Apr;7(4):583-91 [8458575] Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10499-503 [8248136] J Mol Biol. 1994 Jan 14;235(2):424-35 [8289272] Nucleic Acids Res. 1993 Dec 25;21(25):5890-5 [8290349] J Biol Chem. 1994 Feb 4;269(5):3283-9 [8106366] Bioessays. 1996 Sep;18(9):731-8 [8831289] Nucleic Acids Res. 1996 Oct 1;24(19):3685-92 [8871545] J Biol Chem. 1996 Oct 25;271(43):26825-34 [8900164] Nature. 1996 Nov 28;384(6607):379-83 [8934527] Nucleic Acids Res. 1997 Feb 15;25(4):787-93 [9016630] Science. 1997 Feb 14;275(5302):990-3 [9020084] Cell. 1997 Mar 21;88(6):737-40 [9118215] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-11 [9113985] Cell. 1997 Aug 22;90(4):635-47 [9288744] EMBO J. 1997 Oct 1;16(19):5955-65 [9312053] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11205-9 [9326587] Mol Cell Biol. 1997 Dec;17(12):6803-14 [9372911] EMBO J. 1997 Dec 15;16(24):7444-56 [9405373] Mutat Res. 1994 May;314(3):221-31 [7513055] Ann N Y Acad Sci. 1994 Jul 29;726:330-2 [8092696] Nucleic Acids Res. 1995 Jul 25;23(14):2715-23 [7651832] J Bacteriol. 1995 Oct;177(19):5612-21 [7559350] Nucleic Acids Res. 1996 Jun 15;24(12):2324-30 [8710503] Mol Cell Biol. 1996 Aug;16(8):4436-44 [8754844] Mol Cell Biol. 1998 May;18(5):2668-76 [9566886] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Breast cancer: genetic predisposition and exposure to radiation. AN - 69271118; 10559788 AB - The identification of breast cancer susceptibility genes, such as BRCA1, BRCA2, ATM, and p53, has been accompanied by the examination of the effects of radiation in combination with genetic mutations at these loci. Women at high risk for developing breast cancer may respond differently than the general population to low- and high-dose radiation exposures associated with screening and treatment. Epidemiologic studies are being performed to investigate the effects of radiation on subsequent breast cancer development in genetically predisposed individuals. Mouse strains with specific genetic modifications are being created to study the consequence of both inherited mutations and radiation on mammary gland carcinogenesis. Finally, studies investigating DNA damage-response pathways after radiation exposure are being performed. Recent work on the effects of several known or suspected breast cancer susceptibility genes, alone or in combination with radiation, is presented here, and directions for future research are considered. Copyright 1999 Wiley-Liss, Inc. JF - Molecular carcinogenesis AU - Bennett, L M AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 143 EP - 149 VL - 26 IS - 3 SN - 0899-1987, 0899-1987 KW - Index Medicus KW - Animals KW - Humans KW - Mammary Neoplasms, Experimental -- genetics KW - Breast Neoplasms -- genetics KW - Genetic Predisposition to Disease -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Breast Neoplasms -- etiology KW - Neoplasms, Radiation-Induced -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69271118?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+carcinogenesis&rft.atitle=Breast+cancer%3A+genetic+predisposition+and+exposure+to+radiation.&rft.au=Bennett%2C+L+M&rft.aulast=Bennett&rft.aufirst=L&rft.date=1999-11-01&rft.volume=26&rft.issue=3&rft.spage=143&rft.isbn=&rft.btitle=&rft.title=Molecular+carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-02 N1 - Date created - 1999-12-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. AN - 69261900; 10555659 AB - In a recent acute study, amantadine was found to have antidyskinetic effect against levodopa-induced motor complications in patients with Parkinson disease. The longevity of this effect was not addressed but is of interest in light of the controversy in the literature regarding the duration of amantadine's well-established antiparkinsonian action. To determine the duration of the antidyskinetic effect of amantadine in advanced Parkinson disease. One year after completion of an acute, double-blind, placebo-controlled, crossover study, patients returned for re-evaluation of motor symptoms and dyskinesias using a nonrandomized, double-blind, placebo-controlled follow-up paradigm. National Institutes of Health Clinical Center. Seventeen of the original 18 patients with advanced Parkinson disease complicated by dyskinesias and motor fluctuations participated in this study; 1 was lost to follow-up. Thirteen of the 17 individuals had remained on amantadine therapy for the entire year. Ten days prior to the follow-up assessment, amantadine was replaced with identical capsules containing either amantadine or placebo. Parkinsonian symptoms and dyskinesia severity were scored using standard rating scales, while subjects received steady-state intravenous levodopa infusions at the same rate as 1 year earlier. One year after initiation of amantadine cotherapy, its antidyskinetic effect was similar in magnitude (56% reduction in dyskinesia compared with 60% 1 year earlier). Motor complications occurring with the patients' regular oral levodopa regimen also remained improved according to the Unified Parkinson's Disease Rating Scale (UPDRS-IV). The beneficial effects of amantadine on motor response complications are maintained for at least 1 year after treatment initiation. JF - Archives of neurology AU - Metman, L V AU - Del Dotto, P AU - LePoole, K AU - Konitsiotis, S AU - Fang, J AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1383 EP - 1386 VL - 56 IS - 11 SN - 0003-9942, 0003-9942 KW - Antiparkinson Agents KW - 0 KW - Levodopa KW - 46627O600J KW - Amantadine KW - BF4C9Z1J53 KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Cross-Over Studies KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Antiparkinson Agents -- adverse effects KW - Dyskinesia, Drug-Induced -- drug therapy KW - Amantadine -- therapeutic use KW - Dyskinesia, Drug-Induced -- diagnosis KW - Antiparkinson Agents -- therapeutic use KW - Dyskinesia, Drug-Induced -- etiology KW - Amantadine -- blood KW - Levodopa -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69261900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+neurology&rft.atitle=Amantadine+for+levodopa-induced+dyskinesias%3A+a+1-year+follow-up+study.&rft.au=Metman%2C+L+V%3BDel+Dotto%2C+P%3BLePoole%2C+K%3BKonitsiotis%2C+S%3BFang%2C+J%3BChase%2C+T+N&rft.aulast=Metman&rft.aufirst=L&rft.date=1999-11-01&rft.volume=56&rft.issue=11&rft.spage=1383&rft.isbn=&rft.btitle=&rft.title=Archives+of+neurology&rft.issn=00039942&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-23 N1 - Date created - 1999-12-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias. AN - 69242651; 10553990 AB - The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi of parkinsonian monkeys continuously through the "off" and "on" states, and 10 to 15 minutes later during "on with or without dyskinesias," depending on two doses of levodopa. The transition from the "off" to the "on" state was characterized by a decrease (most cells), no change, or an increase in firing rate of individual cells. During dyskinesias, firing rates declined profoundly in almost all cells, with decrements as low as 97% in individual cells. These changes occurred only when dyskinesias were present. The difference in GPi activity between "on" and "on with dyskinesias" suggests that normal motor function in Parkinson's disease critically depends on fine tuning of the basal ganglia output. Dyskinesias result from an imbalanced low GPi discharge, a circumstance that may be susceptible to development of new therapeutic approaches. JF - Annals of neurology AU - Papa, S M AU - Desimone, R AU - Fiorani, M AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 732 EP - 738 VL - 46 IS - 5 SN - 0364-5134, 0364-5134 KW - Antiparkinson Agents KW - 0 KW - Drug Combinations KW - carbidopa, levodopa drug combination KW - Levodopa KW - 46627O600J KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Carbidopa KW - MNX7R8C5VO KW - Index Medicus KW - Animals KW - Eye Movements KW - Electrophysiology -- methods KW - Antiparkinson Agents -- toxicity KW - Antiparkinson Agents -- therapeutic use KW - Motor Activity -- drug effects KW - Macaca mulatta KW - Levodopa -- toxicity KW - Dyskinesias -- physiopathology KW - Dyskinesia, Drug-Induced KW - Neurons -- drug effects KW - Parkinsonian Disorders -- chemically induced KW - Carbidopa -- toxicity KW - Neurons -- physiology KW - Levodopa -- therapeutic use KW - Globus Pallidus -- drug effects KW - Globus Pallidus -- physiopathology KW - Carbidopa -- therapeutic use KW - Parkinsonian Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69242651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+neurology&rft.atitle=Internal+globus+pallidus+discharge+is+nearly+suppressed+during+levodopa-induced+dyskinesias.&rft.au=Papa%2C+S+M%3BDesimone%2C+R%3BFiorani%2C+M%3BOldfield%2C+E+H&rft.aulast=Papa&rft.aufirst=S&rft.date=1999-11-01&rft.volume=46&rft.issue=5&rft.spage=732&rft.isbn=&rft.btitle=&rft.title=Annals+of+neurology&rft.issn=03645134&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-24 N1 - Date created - 1999-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kynostatin and 17beta-estradiol prevent the apoptotic death of human neuroblastoma cells exposed to HIV-1 protease. AN - 69233264; 10545779 AB - A significant number of adult male patients with acquired immunodeficiency syndrome develop cerebral atrophy and progressive brain disorders such as dementia complex and neuropsychiatric problems. Upon entering the brain via activated macrophages or microglias, the human immunodeficiency type 1 virus (HIV-1) may produce cytotoxic factors such as HIV-1 envelope protein (gp120) and protease. Owing to significant proteolysis of nonviral proteins, the protease derived from HIV-1 may be detrimental to brain cells and neurons. Our results revealed that HIV-1 protease, at nanomolar concentrations, was as potent as gp120 in causing neurotoxicity in human neuroblastoma neurotypic SH-SY5Y cells. As shown by the Oncor ApopTag staining procedure, HIV-1 protease significantly increased the number of apoptotic cells over the serum-free controls. Moreover, HIV-1 protease-induced neurotoxicity was blocked by a selective protease inhibitor, kynostatin (KNI-272). Antioxidants such as 17beta-estradiol, melatonin, and S-nitrosoglutathione also prevented protease-induced neurotoxicity. These findings indicate that oxidative proteolysis may mediate HIV-1 protease-induced apoptosis and the degeneration of neurons and other brain cells. Centrally active protease inhibitors and antioxidants may play an important role in preventing cerebral atrophy and associated dementia complex caused by HIV-1. JF - Journal of biomedical science AU - Hawkins, V AU - Shen, Q AU - Chiueh, C C AD - Howard Huges Medical Institute Student Teacher Internship Program, Montgomery County Public School, and National Institutes of Health, Bethesda, MD 20892-1264, USA. PY - 1999 SP - 433 EP - 438 VL - 6 IS - 6 SN - 1021-7770, 1021-7770 KW - Antioxidants KW - 0 KW - HIV Protease Inhibitors KW - Nitroso Compounds KW - Oligopeptides KW - Recombinant Proteins KW - kynostatin 272 KW - 147318-81-8 KW - Estradiol KW - 4TI98Z838E KW - S-Nitrosoglutathione KW - 57564-91-7 KW - HIV Protease KW - EC 3.4.23.- KW - Glutathione KW - GAN16C9B8O KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - AIDS/HIV KW - Melatonin -- pharmacology KW - Recombinant Proteins -- pharmacology KW - Tumor Cells, Cultured KW - Antioxidants -- pharmacology KW - Humans KW - Nitroso Compounds -- pharmacology KW - Glutathione -- pharmacology KW - Glutathione -- analogs & derivatives KW - Neuroblastoma -- pathology KW - HIV Protease -- pharmacology KW - Estradiol -- pharmacology KW - Apoptosis -- drug effects KW - HIV Protease Inhibitors -- pharmacology KW - Oligopeptides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69233264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+biomedical+science&rft.atitle=Kynostatin+and+17beta-estradiol+prevent+the+apoptotic+death+of+human+neuroblastoma+cells+exposed+to+HIV-1+protease.&rft.au=Hawkins%2C+V%3BShen%2C+Q%3BChiueh%2C+C+C&rft.aulast=Hawkins&rft.aufirst=V&rft.date=1999-11-01&rft.volume=6&rft.issue=6&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Journal+of+biomedical+science&rft.issn=10217770&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-16 N1 - Date created - 1999-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment. AN - 69231890; 10549650 AB - Experimental autoimmune uveoretinitis (EAU) in mice is an important model for elucidating basic mechanisms in autoimmune eye disease. The need for pertussis toxin (PTX) as an additional adjuvant to elicit EAU has limited the usefulness of this model in some types of studies by introducing a pleiotropic factor with confounding effects on the immune response. In the present study the authors examined the ability of B10.RIII mice, the most susceptible strain known so far, to develop EAU in response to the retinal antigen, interphotoreceptor retinoid-binding protein (IRBP), and to a major uveitogenic epitope of IRBP, peptide (p)161-180, in the absence of PTX treatment. The data indicate that high disease scores in response to IRBP and p161-180 were found in B10.RIII mice, without the need for PTX as part of the immunization protocol. Unlike the B10.A strain in which appreciable disease did not develop without PTX, B10.RIII mice mounted a high IFN-gamma response to IRBP in the absence of PTX treatment. Interestingly, and unlike the effect with IRBP, in vitro recall response to p161-180 was low in IFN-gamma, despite good EAU scores. The data indicate that an important mechanism through which PTX facilitates induction of cell-mediated autoimmunity is by promoting a Th1 polarization of the immune response. The propensity of B10.RIII mice to mount a more polarized Th1 response to IRBP than other strains may contribute to their ability to develop EAU without pertussis adjuvant. Nevertheless, the induction of EAU by p161-180 in the context of a relatively limited IFN-gamma production indicates that non-Th1- and Th-related mechanisms are likely to act in concert to determine the outcome of disease. JF - Investigative ophthalmology & visual science AU - Silver, P B AU - Chan, C C AU - Wiggert, B AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 2898 EP - 2905 VL - 40 IS - 12 SN - 0146-0404, 0146-0404 KW - Adjuvants, Immunologic KW - 0 KW - Cytokines KW - Eye Proteins KW - Peptide Fragments KW - Retinol-Binding Proteins KW - Virulence Factors, Bordetella KW - interstitial retinol-binding protein KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Reproducibility of Results KW - Cytokines -- biosynthesis KW - Mice KW - Immunity, Cellular -- immunology KW - Vaccination KW - Hypersensitivity, Delayed -- immunology KW - Eye Proteins -- pharmacology KW - Lymphocyte Activation KW - Autoimmunity -- immunology KW - Mice, Mutant Strains KW - Adoptive Transfer KW - Hypersensitivity, Delayed -- etiology KW - Peptide Fragments -- pharmacology KW - Autoimmunity -- drug effects KW - Immunity, Cellular -- drug effects KW - Enzyme-Linked Immunosorbent Assay KW - Th1 Cells -- immunology KW - Retinol-Binding Proteins -- pharmacology KW - Retinitis -- immunology KW - Uveitis -- immunology KW - Retinitis -- chemically induced KW - Autoimmune Diseases -- genetics KW - Virulence Factors, Bordetella -- pharmacology KW - Retinitis -- genetics KW - Uveitis -- genetics KW - Autoimmune Diseases -- chemically induced KW - Adjuvants, Immunologic -- pharmacology KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69231890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=The+requirement+for+pertussis+to+induce+EAU+is+strain-dependent%3A+B10.RIII%2C+but+not+B10.A+mice%2C+develop+EAU+and+Th1+responses+to+IRBP+without+pertussis+treatment.&rft.au=Silver%2C+P+B%3BChan%2C+C+C%3BWiggert%2C+B%3BCaspi%2C+R+R&rft.aulast=Silver&rft.aufirst=P&rft.date=1999-11-01&rft.volume=40&rft.issue=12&rft.spage=2898&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-08 N1 - Date created - 1999-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Perlecan is essential for cartilage and cephalic development. AN - 69231325; 10545953 AB - Perlecan, a large, multi-domain, heparan sulfate proteoglycan originally identified in basement membrane, interacts with extracellular matrix proteins, growth factors and receptors, and influences cellular signalling. Perlecan is present in a variety of basement membranes and in other extracellular matrix structures. We have disrupted the gene encoding perlecan (Hspg2) in mice. Approximately 40% of Hspg2-/- mice died at embryonic day (E) 10.5 with defective cephalic development. The remaining Hspg2-/- mice died just after birth with skeletal dysplasia characterized by micromelia with broad and bowed long bones, narrow thorax and craniofacial abnormalities. Only 6% of Hspg2-/- mice developed both exencephaly and chondrodysplasia. Hspg2-/- cartilage showed severe disorganization of the columnar structures of chondrocytes and defective endochondral ossification. Hspg2-/- cartilage matrix contained reduced and disorganized collagen fibrils and glycosaminoglycans, suggesting that perlecan has an important role in matrix structure. In Hspg2-/- cartilage, proliferation of chondrocytes was reduced and the prehypertrophic zone was diminished. The abnormal phenotypes of the Hspg2-/- skeleton are similar to those of thanatophoric dysplasia (TD) type I, which is caused by activating mutations in FGFR3 (refs 7, 8, 9), and to those of Fgfr3 gain-of-function mice. Our findings suggest that these molecules affect similar signalling pathways. JF - Nature genetics AU - Arikawa-Hirasawa, E AU - Watanabe, H AU - Takami, H AU - Hassell, J R AU - Yamada, Y AD - Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 354 EP - 358 VL - 23 IS - 3 SN - 1061-4036, 1061-4036 KW - Cartilage Oligomeric Matrix Protein KW - 0 KW - Extracellular Matrix Proteins KW - Glycoproteins KW - Heparan Sulfate Proteoglycans KW - Matn1 protein, mouse KW - Matrilin Proteins KW - Proteoglycans KW - RNA, Messenger KW - Receptors, Fibroblast Growth Factor KW - TSP5 protein, human KW - perlecan KW - 143972-95-6 KW - Heparitin Sulfate KW - 9050-30-0 KW - FGFR3 protein, human KW - EC 2.7.10.1 KW - Fgfr3 protein, mouse KW - Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 3 KW - Index Medicus KW - Extracellular Matrix Proteins -- analysis KW - Animals KW - Glycoproteins -- analysis KW - Humans KW - Growth Plate -- pathology KW - Gene Expression KW - Chondrocytes -- pathology KW - Mice, Transgenic KW - RNA, Messenger -- genetics KW - Receptors, Fibroblast Growth Factor -- deficiency KW - Receptors, Fibroblast Growth Factor -- physiology KW - Growth Plate -- metabolism KW - Growth Plate -- abnormalities KW - Chondrocytes -- metabolism KW - Cell Division KW - Receptors, Fibroblast Growth Factor -- genetics KW - RNA, Messenger -- analysis KW - Cell Differentiation KW - Mice KW - Gene Deletion KW - Animals, Newborn KW - Thanatophoric Dysplasia -- genetics KW - Mutagenesis, Insertional KW - Abnormalities, Multiple -- genetics KW - Proteoglycans -- deficiency KW - Cartilage -- abnormalities KW - Head -- growth & development KW - Head -- embryology KW - Proteoglycans -- physiology KW - Cartilage -- growth & development KW - Cartilage -- embryology KW - Proteoglycans -- genetics KW - Cartilage -- metabolism KW - Abnormalities, Multiple -- embryology KW - Heparitin Sulfate -- deficiency KW - Abnormalities, Multiple -- metabolism KW - Heparitin Sulfate -- physiology KW - Heparitin Sulfate -- genetics KW - Head -- abnormalities UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69231325?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Perlecan+is+essential+for+cartilage+and+cephalic+development.&rft.au=Arikawa-Hirasawa%2C+E%3BWatanabe%2C+H%3BTakami%2C+H%3BHassell%2C+J+R%3BYamada%2C+Y&rft.aulast=Arikawa-Hirasawa&rft.aufirst=E&rft.date=1999-11-01&rft.volume=23&rft.issue=3&rft.spage=354&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-07 N1 - Date created - 1999-12-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level. AN - 69231251; 10545404 AB - Mutation of the adenomatous polyposis coli (APC) gene is associated with the earliest stages of colorectal tumorigenesis and appears to be responsible for the hereditary condition familial adenomatous polyposis (FAP). Evidence indicates that cyclooxygenase-2 (COX-2) is induced and at elevated levels in human colorectal cancers and in the polyps of mouse FAP models. We have used HT-29 cells, a human colorectal carcinoma cell line with a mutant carboxy-truncated APC gene, in which intact APC gene has been introduced under the control of an inducible promoter. These HT-29-APC cells provide a suitable model system to examine how COX-2 expression becomes dysregulated after loss of APC function. Induction of full-length APC causes the HT-29-APC cells to undergo apoptosis. However, differentiation, as measured by alkaline phosphatase activity, is not induced upon expression of full-length APC. Full-length APC protein has been shown to bind the intracellular protein beta-catenin and, as a result, the Lef/Tcf transcription factors are down-regulated. Analysis of APC immunoprecipitates demonstrate a time-dependent increase of beta-catenin interacting with full-length APC. Thus, the Lef/Tcf signaling pathway is intact at this point in these cells. Furthermore, upon expression of full-length APC, COX-2 protein expression is down-regulated while COX-2 mRNA levels remain the same. These data indicate that APC plays a role, either directly or indirectly, in the translational regulation of COX-2. Treatment of the HT-29-APC cells with sodium butyrate, an inducer of apoptosis, does not alter COX-2 protein expression. Thus, COX-2 down-regulation appears to be APC specific and not just due to apoptotic induction. APC appears to uniquely regulate COX-2 expression. The mechanism by which COX-2 protein expression is down-regulated in the HT-29-APC cells is under investigation. JF - Carcinogenesis AU - Hsi, L C AU - Angerman-Stewart, J AU - Eling, T E AD - National Institute of Environmental Health Sciences, Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 2045 EP - 2049 VL - 20 IS - 11 SN - 0143-3334, 0143-3334 KW - Adenomatous Polyposis Coli Protein KW - 0 KW - CTNNB1 protein, human KW - CTNNB1 protein, mouse KW - Cytoskeletal Proteins KW - Isoenzymes KW - Membrane Proteins KW - RNA, Messenger KW - Trans-Activators KW - beta Catenin KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Animals KW - Humans KW - Mice KW - RNA, Messenger -- genetics KW - Protein Binding KW - Apoptosis -- genetics KW - RNA, Messenger -- metabolism KW - HT29 Cells KW - Cytoskeletal Proteins -- metabolism KW - Mutation KW - Cell Division -- genetics KW - Cytoskeletal Proteins -- genetics KW - Protein Biosynthesis KW - Colorectal Neoplasms -- pathology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Colorectal Neoplasms -- genetics KW - Colorectal Neoplasms -- enzymology KW - Isoenzymes -- genetics KW - Genes, APC UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69231251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Introduction+of+full-length+APC+modulates+cyclooxygenase-2+expression+in+HT-29+human+colorectal+carcinoma+cells+at+the+translational+level.&rft.au=Hsi%2C+L+C%3BAngerman-Stewart%2C+J%3BEling%2C+T+E&rft.aulast=Hsi&rft.aufirst=L&rft.date=1999-11-01&rft.volume=20&rft.issue=11&rft.spage=2045&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-03 N1 - Date created - 2000-01-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Functional analysis of human FEN1 in Saccharomyces cerevisiae and its role in genome stability. AN - 69228368; 10545607 AB - The flap endonuclease, FEN1, is an evolutionarily conserved component of DNA replication from archaebacteria to humans. Based on in vitro results, it processes Okazaki fragments during replication and is involved in base excision repair. FEN1 removes the last primer ribonucleotide on the lagging strand and it cleaves a 5' flap that may result from strand displacement during replication or during base excision repair. Its biological importance has been revealed largely through studies in the yeast Saccharomyces cerevisiae where deletion of the homologous gene RAD27 results in genome instability and mutagen sensitivity. While the in vivo function of Rad27 has been well characterized through genetic and biochemical approaches, little is understood about the in vivo functions of human FEN1. Guided by our recent results with yeast RAD27, we explored the function of human FEN1 in yeast. We found that the human FEN1 protein complements a yeast rad27 null mutant for a variety of defects including mutagen sensitivity, genetic instability and the synthetic lethal interactions of a rad27 rad51 and a rad27 pol3-01 mutant. Furthermore, a mutant form of FEN1 lacking nuclease function exhibits dominant-negative effects on cell growth and genome instability similar to those seen with the homologous yeast rad27 mutation. This genetic impact is stronger when the human and yeast PCNA-binding domains are exchanged. These data indicate that the human FEN1 and yeast Rad27 proteins act on the same substrate in vivo. Our study defines a sensitive yeast system for the identification and characterization of mutations in FEN1. JF - Human molecular genetics AU - Greene, A L AU - Snipe, J R AU - Gordenin, D A AU - Resnick, M A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 2263 EP - 2273 VL - 8 IS - 12 SN - 0964-6906, 0964-6906 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - Protein Kinases KW - EC 2.7.- KW - CHEK1 protein, human KW - EC 2.7.11.1 KW - Checkpoint Kinase 1 KW - RAD51 protein, S cerevisiae KW - EC 2.7.7.- KW - RAD51 protein, human KW - Rad51 Recombinase KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Flap Endonucleases KW - FEN1 protein, human KW - EC 3.1.11.- KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - Index Medicus KW - Humans KW - DNA-Binding Proteins -- genetics KW - Amino Acid Sequence KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Genetic Complementation Test KW - Molecular Sequence Data KW - Protein Kinases -- genetics KW - Genes, Lethal KW - Mutation KW - Saccharomyces cerevisiae -- genetics KW - Genome, Fungal KW - Exodeoxyribonucleases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69228368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+molecular+genetics&rft.atitle=Functional+analysis+of+human+FEN1+in+Saccharomyces+cerevisiae+and+its+role+in+genome+stability.&rft.au=Greene%2C+A+L%3BSnipe%2C+J+R%3BGordenin%2C+D+A%3BResnick%2C+M+A&rft.aulast=Greene&rft.aufirst=A&rft.date=1999-11-01&rft.volume=8&rft.issue=12&rft.spage=2263&rft.isbn=&rft.btitle=&rft.title=Human+molecular+genetics&rft.issn=09646906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-14 N1 - Date created - 1999-12-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibitory monoclonal antibodies to human cytochrome P450 enzymes: a new avenue for drug discovery. AN - 69226891; 10542439 JF - Trends in pharmacological sciences AU - Gelboin, H V AU - Krausz, K W AU - Gonzalez, F J AU - Yang, T J AD - Laboratory of Molecular Carcinogenesis, National Institute of Health, National Cancer Institute, Building 37, Room 3E24, 37 Convent Drive, Bethesda, MD 20892, USA. GELBOINH@intra.nci.nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 432 EP - 438 VL - 20 IS - 11 SN - 0165-6147, 0165-6147 KW - Antibodies, Monoclonal KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Enzyme Inhibitors KW - Isoenzymes KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Isoenzymes -- antagonists & inhibitors KW - Animals KW - Isoenzymes -- biosynthesis KW - Humans KW - Cytochrome P-450 Enzyme System -- biosynthesis KW - Enzyme Inhibitors -- pharmacology KW - Antibodies, Monoclonal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69226891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Trends+in+pharmacological+sciences&rft.atitle=Inhibitory+monoclonal+antibodies+to+human+cytochrome+P450+enzymes%3A+a+new+avenue+for+drug+discovery.&rft.au=Gelboin%2C+H+V%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BYang%2C+T+J&rft.aulast=Gelboin&rft.aufirst=H&rft.date=1999-11-01&rft.volume=20&rft.issue=11&rft.spage=432&rft.isbn=&rft.btitle=&rft.title=Trends+in+pharmacological+sciences&rft.issn=01656147&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-13 N1 - Date created - 1999-12-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serologic evidence of heparin sensitization in cancer patients receiving heparin flushes of venous access devices. AN - 69220238; 10541985 AB - Cancer patients with venous access devices (VADs) often receive daily flushes of heparin. Even this relatively small heparin exposure has been reported to induce immune-mediated thrombocytopenia. To estimate how frequently this occurs we tested for heparin-related antibodies in 49 patients receiving daily heparin flushes of their VADs. Although one-third of the patients showed evidence of heparin sensitization on at least one occasion during their surveillance, their antibody titers were generally low and typical of those found in other cohorts of patients who become sensitized to heparin but do not develop secondary thrombocytopenia. However, one patient developed a positive serotonin release assay indicative of a more significant sensitization, but without thrombocytopenia. Therefore, our observations suggest that heparin-induced thrombocytopenia (HIT) related to heparin flushes of VADs is uncommon but still an important diagnosis to entertain. JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer AU - Mayo, D J AU - Cullinane, A M AU - Merryman, P K AU - Horne, M K AD - Hematology Service, Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 425 EP - 427 VL - 7 IS - 6 SN - 0941-4355, 0941-4355 KW - Antibodies KW - 0 KW - Anticoagulants KW - Serotonin KW - 333DO1RDJY KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Humans KW - Aged KW - Population Surveillance KW - Thrombocytopenia -- immunology KW - Serotonin -- secretion KW - Adult KW - Cohort Studies KW - Thrombocytopenia -- chemically induced KW - Enzyme-Linked Immunosorbent Assay KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Platelet Count KW - Heparin -- administration & dosage KW - Antibodies -- blood KW - Anticoagulants -- adverse effects KW - Heparin -- immunology KW - Anticoagulants -- immunology KW - Immunization KW - Heparin -- adverse effects KW - Neoplasms -- immunology KW - Catheters, Indwelling KW - Anticoagulants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69220238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.atitle=Serologic+evidence+of+heparin+sensitization+in+cancer+patients+receiving+heparin+flushes+of+venous+access+devices.&rft.au=Mayo%2C+D+J%3BCullinane%2C+A+M%3BMerryman%2C+P+K%3BHorne%2C+M+K&rft.aulast=Mayo&rft.aufirst=D&rft.date=1999-11-01&rft.volume=7&rft.issue=6&rft.spage=425&rft.isbn=&rft.btitle=&rft.title=Supportive+care+in+cancer+%3A+official+journal+of+the+Multinational+Association+of+Supportive+Care+in+Cancer&rft.issn=09414355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Active and passive smoking and the occurrence of natural menopause. AN - 69216120; 10535795 AB - We examined smoking in relation to natural menopause in 543 women who prospectively recorded menstrual data from their 20s. Mean age at natural menopause was 0.8 years younger (95% CL = -1.5, -0.0) in 98 women who smoked at menopause compared with 362 never-smokers (RR 1.3, 95% CI = 1.0-1.7). We did not observe a decrease in age at natural menopause in former smokers, a dose-response among current smokers, or a lower age at menopause with passive smoke exposure at home. These results suggest that the effect of smoking on ovarian senescence is limited to active smoking during the menopausal transition. JF - Epidemiology (Cambridge, Mass.) AU - Cooper, G S AU - Sandler, D P AU - Bohlig, M AD - Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 771 EP - 773 VL - 10 IS - 6 SN - 1044-3983, 1044-3983 KW - Tobacco Smoke Pollution KW - 0 KW - Index Medicus KW - Prospective Studies KW - Humans KW - Adult KW - Middle Aged KW - Female KW - Proportional Hazards Models KW - Menopause -- physiology KW - Smoking KW - Ovary -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69216120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epidemiology+%28Cambridge%2C+Mass.%29&rft.atitle=Active+and+passive+smoking+and+the+occurrence+of+natural+menopause.&rft.au=Cooper%2C+G+S%3BSandler%2C+D+P%3BBohlig%2C+M&rft.aulast=Cooper&rft.aufirst=G&rft.date=1999-11-01&rft.volume=10&rft.issue=6&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Epidemiology+%28Cambridge%2C+Mass.%29&rft.issn=10443983&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. AN - 69214892; 10535870 AB - Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a T-helper 1 (Th1) T cell-mediated inflammation that is rapidly reversed by administration of anti-interleukin (IL) 12. This study sought to define the mechanism of this curative effect. Cells and tissue from mice with TNBS colitis receiving treatment with anticytokines were analyzed for phenotype, cytokine production, and apoptosis. In initial studies, we found that treatment of mice with TNBS-induced colitis with anti-IL-12 was more effective than with anti-interferon (IFN)-gamma, and that anti-IL-12 led to complete normalization of IFN-gamma production by lamina propria T cells ex vivo, whereas anti-IFN-gamma did not. These data suggesting that anti-IL-12 leads to reversal of colitis by elimination of the Th1 T cells were substantiated by studies showing that anti-IL-12 treatment led to increased numbers of apoptotic cells in the lamina propria and spleen by both TUNEL staining of tissues and dispersed spleen cell populations. Finally, we found that the observed apoptosis was mediated by the Fas pathway because (1) MRL/MpJ-lpr(fas) mice lacking Fas function develop colitis that responds poorly to treatment with anti-IL-12; and (2) SJL/J mice with TNBS colitis that received Fas-Fc to block the Fas pathway were resistant to anti-IL-12 treatment. These studies show that a main mechanism of action of anti-IL-12 in TNBS-induced colitis is the induction of Fas-mediated apoptosis of the Th1 T cells, causing inflammation. JF - Gastroenterology AU - Fuss, I J AU - Marth, T AU - Neurath, M F AU - Pearlstein, G R AU - Jain, A AU - Strober, W AD - Mucosal Immunity Section, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1078 EP - 1088 VL - 117 IS - 5 SN - 0016-5085, 0016-5085 KW - Antibodies KW - 0 KW - Antigens, CD95 KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Trinitrobenzenesulfonic Acid KW - 8T3HQG2ZC4 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Mice, Inbred Strains KW - Animals KW - Antigens, CD95 -- metabolism KW - Antigens, CD95 -- physiology KW - Mice, Inbred MRL lpr KW - T-Lymphocytes -- physiology KW - Mice KW - Interferon-gamma -- immunology KW - T-Lymphocytes -- drug effects KW - Male KW - Interleukin-12 -- immunology KW - Antibodies -- therapeutic use KW - Th1 Cells -- drug effects KW - Apoptosis -- drug effects KW - Colitis -- physiopathology KW - Colitis -- chemically induced KW - Colitis -- drug therapy KW - Th1 Cells -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69214892?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gastroenterology&rft.atitle=Anti-interleukin+12+treatment+regulates+apoptosis+of+Th1+T+cells+in+experimental+colitis+in+mice.&rft.au=Fuss%2C+I+J%3BMarth%2C+T%3BNeurath%2C+M+F%3BPearlstein%2C+G+R%3BJain%2C+A%3BStrober%2C+W&rft.aulast=Fuss&rft.aufirst=I&rft.date=1999-11-01&rft.volume=117&rft.issue=5&rft.spage=1078&rft.isbn=&rft.btitle=&rft.title=Gastroenterology&rft.issn=00165085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-08 N1 - Date created - 1999-12-08 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Gastroenterology. 1999 Nov;117(5):1238-41 [10535889] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin. AN - 69213969; 10534697 AB - Overexpression of the oncogene erbB-2 contributes to chemoresistance in various malignant tumors including lung cancer. The aim of this study was to investigate whether depletion of the erbB-2 gene product (p185) by 17-allylamino 17-demethoxygeldanamycin would sensitize lung cancer cells to paclitaxel (Taxol) in vitro. Paclitaxel cytotoxicity was evaluated in a panel of non-small cell lung cancer cell lines that expressed varying levels of p185 by means in vitro proliferation assays and 2 drug combination schedules. Cell cycle kinetics and apoptosis after exposure to paclitaxel or paclitaxel plus 17-allylamino 17-demethoxygeldanamycin were analyzed by flow cytometry. The 17-allylamino 17-demethoxygeldanamycin treatment efficiently depleted p185 expression in lung cancer cells. Concurrent exposure of these cells to paclitaxel and 17-allylamino 17-demethoxygeldanamycin significantly enhanced paclitaxel-mediated cytotoxicity, particularly in cells which overexpressed p185. There was a 1.3 to more than 20-fold reduction of paclitaxel 50% inhibitory concentration values in those cells that were responding positively to the drug combination. Significant induction of apoptosis was observed after treatment of cells with the combination of paclitaxel and 17-allylamino 17-demethoxygeldanamycin. The combination cytotoxic effect was only additive in cells expressing low levels of p185. In contrast, of lung cancer cells with exposure to 17-allylamino 17-demethoxygeldanamycin before combined paclitaxel and 17-allylamino 17-demethoxygeldanamycin exposure actually rendered the cells refractory to paclitaxel cytotoxicity. The compound 17-allylamino 17-demethoxygeldanamycin sensitizes non-small cell lung cancer cells expressing high levels of p185 to paclitaxel-mediated growth arrest and apoptosis. These preclinical data support the evaluation of the combination of paclitaxel and 17-allylamino 17-demethoxygeldanamycin in the treatment of patients with lung cancer whose tumors exhibit p185 overexpression. JF - The Journal of thoracic and cardiovascular surgery AU - Nguyen, D M AU - Chen, A AU - Mixon, A AU - Schrump, D S AD - Section of Thoracic Oncology, Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. Dao_Nguyen@nih.gov Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 908 EP - 915 VL - 118 IS - 5 SN - 0022-5223, 0022-5223 KW - Antibiotics, Antineoplastic KW - 0 KW - Antineoplastic Agents, Phytogenic KW - Benzoquinones KW - Enzyme Inhibitors KW - Lactams, Macrocyclic KW - Rifabutin KW - 1W306TDA6S KW - tanespimycin KW - 4GY0AVT3L4 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Paclitaxel KW - P88XT4IS4D KW - Abridged Index Medicus KW - Index Medicus KW - Apoptosis KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Enzyme Inhibitors -- pharmacology KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Cell Line KW - Receptor, ErbB-2 -- biosynthesis KW - Carcinoma, Non-Small-Cell Lung -- metabolism KW - Antineoplastic Agents, Phytogenic -- toxicity KW - Rifabutin -- analogs & derivatives KW - Paclitaxel -- toxicity KW - Antibiotics, Antineoplastic -- pharmacology KW - Rifabutin -- pharmacology KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69213969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.atitle=Sequence-dependent+enhancement+of+paclitaxel+toxicity+in+non-small+cell+lung+cancer+by+17-allylamino+17-demethoxygeldanamycin.&rft.au=Nguyen%2C+D+M%3BChen%2C+A%3BMixon%2C+A%3BSchrump%2C+D+S&rft.aulast=Nguyen&rft.aufirst=D&rft.date=1999-11-01&rft.volume=118&rft.issue=5&rft.spage=908&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+thoracic+and+cardiovascular+surgery&rft.issn=00225223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-23 N1 - Date created - 1999-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Domain exchangeability between the multidrug transporter (MDR1) and phosphatidylcholine flippase (MDR2). AN - 69206834; 10531406 AB - Multidrug resistance (MDR) mediated by P-glycoprotein (MDR1) is clinically significant. Understanding how MDR1 substrate specificity is determined will help to overcome MDR to improve cancer treatment. One potential approach to achieve this goal is to study chimeras of MDR1 and its homolog MDR2 (also called MDR3), which has been identified as a phosphatidylcholine flippase. With an approach involving exchanging homologous segments of MDR1 and MDR2 and site-directed mutagenesis, we previously demonstrated MDR1 residues Q330, V331, and L332 in transmembrane domain 6 (TM6) are essential for multidrug transport activity; substituting these residues allows the N-terminal transmembrane region of MDR2 to support MDR1 activity. To further determine the exchangeability between MDR1 and MDR2, we constructed additional MDR1/MDR2 chimeras. We found that the N-terminal half of MDR1 and MDR2 was mostly exchangeable except for a few residues in TM6. However, this degree of exchangeability was not found in the C-terminal half of MDR1 and MDR2. In addition, with substitution of MDR1 residues 318-332 (TM6) and 937-994 (TM11-12), MDR2 had relatively normal affinity for MDR1 substrates, but it did not have multidrug transporter activity. These results suggest that the inability of MDR2 to transport most MDR1 drugs efficiently may be due to failure of those drugs to stimulate ATPase and activate transport as well as to decreased drug binding. JF - Molecular pharmacology AU - Zhou, Y AU - Gottesman, M M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 997 EP - 1004 VL - 56 IS - 5 SN - 0026-895X, 0026-895X KW - P-Glycoprotein KW - 0 KW - P-Glycoproteins KW - Phosphatidylcholines KW - Recombinant Fusion Proteins KW - multidrug resistance protein 3 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - HeLa Cells KW - Drug Resistance, Multiple -- physiology KW - Humans KW - Protein Structure, Tertiary KW - Biological Transport, Active KW - Binding Sites KW - P-Glycoproteins -- genetics KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - ATP-Binding Cassette Transporters -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - P-Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69206834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Domain+exchangeability+between+the+multidrug+transporter+%28MDR1%29+and+phosphatidylcholine+flippase+%28MDR2%29.&rft.au=Zhou%2C+Y%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Zhou&rft.aufirst=Y&rft.date=1999-11-01&rft.volume=56&rft.issue=5&rft.spage=997&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-24 N1 - Date created - 1999-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p53 in neuronal apoptosis: evidence that GAPDH is upregulated by p53. AN - 69205794; 10531467 AB - We recently reported that cytosine arabinoside (AraC)-induced apoptosis of cerebellar neurons involves the overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The present study was undertaken to investigate whether p53 and/or Bax overexpression participates in the AraC-induced apoptosis of cerebellar granule cells and, if so, the relationship between p53 induction and GAPDH overexpression in these cells. AraC-induced apoptosis of cerebellar granule cells was preceded by an increase in levels of p53 mRNA and protein detected between 1 and 8 hr after treatment. The mRNA level for a p53 target gene, Bax, was also increased. The increase in GAPDH mRNA lasted longer than that of either p53 or Bax, and the level of GAPDH protein in the particulate fraction increased after induction of GAPDH mRNA. The antisense oligonucleotide to p53 protected granule cells from AraC-induced chromatin condensation, internucleosomal cleavage, and apoptotic death. The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels. Conversely, the suppression of GAPDH expression and subsequent attenuation of apoptosis of granule cells by GAPDH antisense oligonucleotide did not influence the expression of p53 or Bax. Cerebellar granule cells prepared from p53 knock-out mice were resistant to AraC toxicity, and the p53 gene knock-out suppressed AraC-upregulated GAPDH expression. Moreover, infection of PC12 cells with an adenoviral vector containing p53 gene dramatically increased GAPDH expression and triggered cell apoptosis. These results suggest that AraC-induced apoptosis of cerebellar granule cells involves the expression of both GAPDH and p53 and that, similar to Bax, GAPDH is upregulated by p53 after exposure to the apoptotic insult. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Chen, R W AU - Saunders, P A AU - Wei, H AU - Li, Z AU - Seth, P AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/11/01/ PY - 1999 DA - 1999 Nov 01 SP - 9654 EP - 9662 VL - 19 IS - 21 KW - Bax protein, mouse KW - 0 KW - Bax protein, rat KW - Oligodeoxyribonucleotides, Antisense KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Proteins KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Cytarabine KW - 04079A1RDZ KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Index Medicus KW - Animals KW - Recombinant Proteins -- biosynthesis KW - Genes, p53 -- drug effects KW - Mice KW - Oligodeoxyribonucleotides, Antisense -- pharmacology KW - Mice, Knockout KW - Cytarabine -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Gene Expression Regulation, Enzymologic KW - Transfection KW - Gene Expression Regulation -- drug effects KW - Proto-Oncogene Proteins -- genetics KW - PC12 Cells KW - Cerebellum -- cytology KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- metabolism KW - Apoptosis -- physiology KW - Neurons -- cytology KW - Neurons -- physiology KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Cerebellum -- physiology KW - Tumor Suppressor Protein p53 -- deficiency KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69205794?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Involvement+of+glyceraldehyde-3-phosphate+dehydrogenase+%28GAPDH%29+and+p53+in+neuronal+apoptosis%3A+evidence+that+GAPDH+is+upregulated+by+p53.&rft.au=Chen%2C+R+W%3BSaunders%2C+P+A%3BWei%2C+H%3BLi%2C+Z%3BSeth%2C+P%3BChuang%2C+D+M&rft.aulast=Chen&rft.aufirst=R&rft.date=1999-11-01&rft.volume=19&rft.issue=21&rft.spage=9654&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parenting Strategies regarding Teen Behavior: Parent and Teen Perceptions AN - 61462550; 200011189 AB - Examines parents' awareness of their adolescents' alcohol-related behavior & compares parent & teenager perceptions of parent strategies to manage teen behavior, drawing on telephone interview data from 428 parents & their adolescents in MD. Parents underestimated their adolescents' alcohol-related behavior. Although most parents reported appropriate parenting strategies, they relied primarily on passive strategies in a limited repertoire to supervise teen behavior. Parent education programs should foster proactive parenting by broadening parents' repertoire of strategies to monitor & manage their teens' behavior. 5 Tables, 24 References. Adapted from the source document. JF - American Journal of Health Behavior AU - Haynie, Denise L AU - Beck, Kenneth H AU - Crump, Aria Davis AU - Shattuck, Teresa AU - Simons-Morton, Bruce AD - Division Epidemiology/Statistics/Prevention Research, NICHD, National Instits Health, Bethesda, MD Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 403 EP - 414 VL - 23 IS - 6 SN - 1087-3244, 1087-3244 KW - Parent Training KW - Parental Attitudes KW - Drinking Behavior KW - Maryland KW - Childrearing Practices KW - Parents KW - Parent Child Relations KW - Knowledge KW - Adolescents KW - article KW - 1939: the family and socialization; adolescence & youth KW - 1941: the family and socialization; sociology of the family, marriage, & divorce UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/61462550?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Asocabs&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Health+Behavior&rft.atitle=Parenting+Strategies+regarding+Teen+Behavior%3A+Parent+and+Teen+Perceptions&rft.au=Haynie%2C+Denise+L%3BBeck%2C+Kenneth+H%3BCrump%2C+Aria+Davis%3BShattuck%2C+Teresa%3BSimons-Morton%2C+Bruce&rft.aulast=Haynie&rft.aufirst=Denise&rft.date=1999-11-01&rft.volume=23&rft.issue=6&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Health+Behavior&rft.issn=10873244&rft_id=info:doi/ LA - English DB - Sociological Abstracts N1 - Date revised - 2007-04-01 N1 - Last updated - 2016-09-28 N1 - CODEN - AJHBF6 N1 - SubjectsTermNotLitGenreText - Parent Child Relations; Childrearing Practices; Adolescents; Drinking Behavior; Parental Attitudes; Parents; Knowledge; Parent Training; Maryland ER - TY - JOUR T1 - Child care and mother-child interaction in the first 3 years of life AN - 57718071; 150300 AB - Examined relations between nonmaternal child care and ratings of maternal sensitivity and child positive engagement at 6, 15, 24 and 36 months for 1,274 mothers and their children participating in the National Institute of Child Health and Human Development Study of Early Child Care. Found that child care was a small but significant predictor of maternal sensitivity and child engagement. More hours of child care predicted less maternal sensitivity and less positive child engagement. Effects were much smaller than effects of maternal education but similar in size to effects of maternal depression and child difficult temperament. (Original abstract - amended) JF - Developmental Psychology AU - NICHD Early Child Care Research Network AD - NICHD Early Child Care Research Network Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 1399 EP - 1413 VL - 35 IS - 6 SN - 0012-1649, 0012-1649 KW - Mother-Infant interactions KW - Relationship KW - Child care UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/57718071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aassia&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+Psychology&rft.atitle=Child+care+and+mother-child+interaction+in+the+first+3+years+of+life&rft.au=NICHD+Early+Child+Care+Research+Network&rft.aulast=NICHD+Early+Child+Care+Research+Network&rft.aufirst=&rft.date=1999-11-01&rft.volume=35&rft.issue=6&rft.spage=1399&rft.isbn=&rft.btitle=&rft.title=Developmental+Psychology&rft.issn=00121649&rft_id=info:doi/ LA - English DB - Applied Social Sciences Index & Abstracts (ASSIA) N1 - Date revised - 2001-08-07 N1 - Document feature - refs. tbls. N1 - Last updated - 2016-09-27 N1 - CODEN - DEVPA9 N1 - SubjectsTermNotLitGenreText - Mother-Infant interactions; Relationship; Child care ER - TY - JOUR T1 - Ancestral primate viewed AN - 52397382; 2000-010113 JF - Nature (London) AU - O'Brien, Stephen J AU - Stanyon, Roscoe Y1 - 1999/11// PY - 1999 DA - November 1999 SP - 365 EP - 366 PB - Macmillan Journals, London VL - 402 IS - 6760 SN - 0028-0836, 0028-0836 KW - Chordata KW - phylogeny KW - Mammalia KW - biologic evolution KW - molecular biology KW - Primates KW - Theria KW - DNA KW - Vertebrata KW - hybridization KW - Eutheria KW - Tetrapoda KW - species diversity KW - 11:Vertebrate paleontology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52397382?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+%28London%29&rft.atitle=Ancestral+primate+viewed&rft.au=O%27Brien%2C+Stephen+J%3BStanyon%2C+Roscoe&rft.aulast=O%27Brien&rft.aufirst=Stephen&rft.date=1999-11-01&rft.volume=402&rft.issue=6760&rft.spage=365&rft.isbn=&rft.btitle=&rft.title=Nature+%28London%29&rft.issn=00280836&rft_id=info:doi/ L2 - http://www.nature.com/nature/index.html LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2000-01-01 N1 - Number of references - 14 N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - biologic evolution; Chordata; DNA; Eutheria; hybridization; Mammalia; molecular biology; phylogeny; Primates; species diversity; Tetrapoda; Theria; Vertebrata ER - TY - JOUR T1 - Child Care and Mother-Child Interaction in the First 3 Years of Life* AN - 1791705274 JF - Developmental Psychology Y1 - 1999/11/01/ PY - 1999 DA - 1999 Nov 01 SP - 1399 CY - Washington PB - American Psychological Association VL - 35 IS - 6 SN - 0012-1649 KW - Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791705274?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apio&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+Psychology&rft.atitle=Child+Care+and+Mother-Child+Interaction+in+the+First+3+Years+of+Life*&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1999-11-01&rft.volume=35&rft.issue=6&rft.spage=1399&rft.isbn=&rft.btitle=&rft.title=Developmental+Psychology&rft.issn=00121649&rft_id=info:doi/ DB - Periodicals Index Online N1 - Last updated - 2016-05-27 ER - TY - JOUR T1 - Evaluation of Novel Human Immunodeficiency Virus Type 1 Gag DNA Vaccines for Protein Expression in Mammalian Cells and Induction of Immune Responses AN - 17470859; 4673338 AB - Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are an important parameter of host defenses that limit viral replication after infection. Induction of effective CTL against conserved viral proteins such as Gag may be essential to the development of a safe and effective HIV type 1 (HIV- 1) vaccine. DNA vaccination represents a novel strategy for inducing potent CD8 super(+) CTL responses in vivo. However, expression of HIV-1 structural proteins by DNA vectors has been hampered by a stringent requirement for coexpression with other viral components, such as Rev and RRE. Furthermore, even with Rev and RRE present, the level of expression of HIV-1 Gag, Pol, or Env is very low in murine cells. These problems have limited our ability to address the key issue of how to generate effective CTL responses to Gag in a mouse model. To overcome this problem, we compared several novel DNA expression vectors for HIV-1 Gag protein expression in primate and mouse cells and for generating immune responses in mice after DNA vaccination. A DNA vector containing wild type HIV-1 gag coding sequences did not induce detectable Gag expression in any of the cells tested. Attempts to increase nuclear export of Gag expression RNA by adding the constitutive transport element yielded only a moderate increase in Gag expression in monkey-derived COS cells and an even lower increase in Gag expression in HeLa cells or several mouse cell lines. In contrast silent-site mutations in the HIV-1 gag coding sequences significantly increased Gag expression levels in all cells tested. Furthermore, this construct induced both Gag-specific antibody and CTL responses in mice after DNA vaccination. Using this construct, we achieved stable expression of HIV-1 Gag in the mouse cell line p815 which can now be used as a target cell for measuring HIV-1 Gag-specific CTL responses in immunized mice. The DNA vectors described in this study should make it possible to systematically evaluate the approaches for maximizing the induction of CTL responses against HIV-1 Gag in mouse and other animal systems. JF - Journal of Virology AU - Qiu, J AU - Song, R AU - Dettenhofer, M AU - Tian, C AU - August, T AU - Felber, B K AU - Pavlakis, G N AU - Yu, X AD - ABL-Basic Research Program, Bldg. 535, Rm. 210, NCI-FCRDC Frederick, MD 21702-1201, pavlakis@ncifcrf.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 9145 EP - 9152 VL - 73 IS - 11 SN - 0022-538X, 0022-538X KW - mice KW - HIV-1 KW - man KW - immunology KW - DNA vaccines KW - Gag protein KW - gag gene KW - gag protein KW - human immunodeficiency virus 1 KW - pol protein KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Biochemistry Abstracts 2: Nucleic Acids KW - Acquired immune deficiency syndrome KW - Mammalian cells KW - Envelope protein KW - Human immunodeficiency virus 1 KW - Lymphocytes T KW - Killer cells KW - Immune response KW - Vaccines KW - F 06807:Active immunization KW - A 01097:Viruses KW - V 22003:AIDS: Immunological aspects KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17470859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Evaluation+of+Novel+Human+Immunodeficiency+Virus+Type+1+Gag+DNA+Vaccines+for+Protein+Expression+in+Mammalian+Cells+and+Induction+of+Immune+Responses&rft.au=Qiu%2C+J%3BSong%2C+R%3BDettenhofer%2C+M%3BTian%2C+C%3BAugust%2C+T%3BFelber%2C+B+K%3BPavlakis%2C+G+N%3BYu%2C+X&rft.aulast=Qiu&rft.aufirst=J&rft.date=1999-11-01&rft.volume=73&rft.issue=11&rft.spage=9145&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Vaccines; Mammalian cells; Lymphocytes T; Killer cells; Acquired immune deficiency syndrome; Immune response; Envelope protein ER - TY - JOUR T1 - Methods for Studying Prion Protein (PrP) Metabolism and the Formation of Protease-Resistant PrP in Cell Culture and Cell-Free Systems: An Update AN - 17461731; 4667041 AB - Transmissible spongiform encephalopathies (TSE) or prion diseases result in aberrant metabolism of prion protein (PrP) and the accumulation of a protease-resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of PrP biosynthesis, intracellular trafficking, and degradation has been studied in a variety of tissue culture cells. Pulse-chase metabolic labeling studies in scrapie-infected cells indicated that PrP-res is made posttranslationally from an apparently normal protease-sensitive precursor, PrP-sen, after the latter reaches the cell surface. Cell-free reactions have provided evidence that PrP-res itself can induce the conversion of PrP-sen to PrP-res in a highly species- and strain-specific manner. These studies have shed light on the mechanism of PrP-res formation and suggest molecular bases for TSE species barrier effects and agent strain propagation. JF - Molecular Biotechnology AU - Caughey, B AU - Raymond, G J AU - Priola, SA AU - Kocisko, DA AU - Race, R E AU - Bessen, R A AU - Lansbury, PT Jr AU - Chesebro, B AD - NIH Rocky Mountain Laboratories, 903 S. 4th St., Hamilton, MT 59840, USA, byron_caughey@nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 45 EP - 55 VL - 13 IS - 1 SN - 1073-6085, 1073-6085 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Prion protein KW - Cell-free system KW - Proteinase KW - Cell culture KW - W3 33340:Other proteins, peptides, amino acids KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17461731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=Methods+for+Studying+Prion+Protein+%28PrP%29+Metabolism+and+the+Formation+of+Protease-Resistant+PrP+in+Cell+Culture+and+Cell-Free+Systems%3A+An+Update&rft.au=Caughey%2C+B%3BRaymond%2C+G+J%3BPriola%2C+SA%3BKocisko%2C+DA%3BRace%2C+R+E%3BBessen%2C+R+A%3BLansbury%2C+PT+Jr%3BChesebro%2C+B&rft.aulast=Caughey&rft.aufirst=B&rft.date=1999-11-01&rft.volume=13&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Prion protein; Cell culture; Proteinase; Cell-free system ER - TY - JOUR T1 - Reconstitution Studies Using the Helical and Carboxy-Terminal Domains of Enzyme I of the Phosphoenolpyruvate:Sugar Phosphotransferase System AN - 17455246; 4662038 AB - Enzyme I of the bacterial phosphoenolpyruvate:sugar phosphotransferase system can be phosphorylated by PEP on an active-site histidine residue, localized to a cleft between an alpha -helical domain and an alpha / beta domain on the amino terminal half of the protein. The phosphoryl group on the active-site histidine can be passed to an active-site histidine residue of HPr. It has been proposed that the major interaction between enzyme I and HPr occurs via the alpha -helical domain of enzyme I. The isolated recombinant alpha -helical domain (residues 25-145) with similar to 80% alpha -helices as well as enzyme I deficient in that domain [EI( Delta HD)] with similar to 50% alpha -helix content from M. capricolum were used to further elucidate the nature of the enzyme I-HPr complex. Isothermal titration calorimetry demonstrated that HPr binds to the alpha -helical domain and intact enzyme I with K' sub(A) = 5 x 10 super(4) and 1.4 x 10 super(5) M super(-1) at pH 7.5 and 25 degree C, respectively, but not to EI( Delta HD), which contains the active-site histidine of enzyme I and can be autophosphorylated by PEP. In vitro reconstitution experiments with proteins from both M. capricolum and E. coli showed that EI( Delta HD) can donate its bound phosphoryl group to HPr in the presence of the isolated alpha -helical domain. Furthermore, M. capricolum recombinant C-terminal domain of enzyme I (EIC) was shown to reconstitute phosphotransfer activity with recombinant N-terminal domain (EIN) approximately 5% as efficiently as the HD-EI( Delta HD) pair. Recombinant EIC strongly self-associates (K' sub(A) approximately 10 super(10) M super(-1)) in comparison to dimerization constants of 10 super(5)-10 super(7) M super(-1) measured for EI and EI( Delta HD). JF - Biochemistry (Washington) AU - Zhu, P-P AU - Szczepanowski, R H AU - Nosworthy, N J AU - Ginsburg, A AU - Peterkofsky, A AD - National Institutes of Health, Building 36, Room 4C-11, Bethesda, MD 20892, USA, alan@codon.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 15470 EP - 15479 VL - 38 IS - 47 SN - 0006-2960, 0006-2960 KW - reconstitution KW - enzyme I KW - phosphoenolpyruvate:sugar phosphotransferase KW - Microbiology Abstracts B: Bacteriology KW - Phosphorylation KW - Escherichia coli KW - Active sites KW - Helix KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17455246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Reconstitution+Studies+Using+the+Helical+and+Carboxy-Terminal+Domains+of+Enzyme+I+of+the+Phosphoenolpyruvate%3ASugar+Phosphotransferase+System&rft.au=Zhu%2C+P-P%3BSzczepanowski%2C+R+H%3BNosworthy%2C+N+J%3BGinsburg%2C+A%3BPeterkofsky%2C+A&rft.aulast=Zhu&rft.aufirst=P-P&rft.date=1999-11-01&rft.volume=38&rft.issue=47&rft.spage=15470&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi991680p LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Active sites; Helix; Phosphorylation DO - http://dx.doi.org/10.1021/bi991680p ER - TY - JOUR T1 - Structural requirements for marbox function in transcriptional activation of marlsoxlrob regulon promoters in Escherichia coli: sequence, orientation and spatial relationship to the core promoter AN - 17446900; 4652639 AB - The promoters of the marlsoxlrob regulon of Escherichia coli contain a binding site (marbox) for the homologous transcriptional activators MarA, SoxS and Rob. In spite of data from footprinting studies, the marbox has not been precisely defined because of its degeneracy and asymmetry and seemingly variable location with respect to the -10 and -35 hexamers for RNA polymerase (RNP) binding. Here, we use DNA retardation studies and hybrid promoters to identify optimally binding 20 bp minimal marboxes from a number of promoters. This has yielded a more defined marbox consensus sequence (AYnGCACnnWnnRYYAAAYn) and has led to the demonstration that some marboxes are inverted relative to others. Using transcriptional fusions to lacZ, we have found that only one marbox orientation is functional at a given location. Moreover, the functional orientation is determined by marbox location: marboxes that are 15 or more basepairs upstream of the -35 hexamer are oriented opposite those closer to the -35 hexamer. Marbox orientation and the spacing between marbox and signals for RNP binding are critical for transcriptional activation, presumably to align MarA with RNP. JF - Molecular Microbiology AU - Martin, R G AU - Gillette, W K AU - Rhee, S AU - Rosner, J L AD - Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, Bldg. 5, Rm. 333, NIH, Bethesda, MD 20892-0560, USA, rgmartin@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 431 EP - 441 VL - 34 IS - 3 SN - 0950-382X, 0950-382X KW - MarA protein KW - Rob protein KW - SoxS protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - DNA-directed RNA polymerase KW - Footprinting KW - Transcription factors KW - Transcription activators KW - Escherichia coli KW - Transcription activation KW - J 02726:RNA and ribosomes KW - N 14551:Virus & phage infections UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17446900?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Structural+requirements+for+marbox+function+in+transcriptional+activation+of+marlsoxlrob+regulon+promoters+in+Escherichia+coli%3A+sequence%2C+orientation+and+spatial+relationship+to+the+core+promoter&rft.au=Martin%2C+R+G%3BGillette%2C+W+K%3BRhee%2C+S%3BRosner%2C+J+L&rft.aulast=Martin&rft.aufirst=R&rft.date=1999-11-01&rft.volume=34&rft.issue=3&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Transcription activators; Transcription activation; DNA-directed RNA polymerase; Footprinting; Transcription factors ER - TY - JOUR T1 - Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochrome P450 21-hydroxylase into the adrenal gland of 21-hydroxylase-deficient mice AN - 17444941; 4652505 AB - 21-Hydroxylase deficiency, a potentially fatal disease due to deletions or mutations of the cytochrome P450 21-hydroxylase gene (CYP21), causes congenital adrenal hyperplasia (CAH) with low or absent glucocorticoid and mineralocorticoid production. The feasibility of gene therapy for CAH was studied using 21OH-deficient mice (21OH-) and a replication-deficient adenovirus containing the genomic sequence of human CYP21 (hAdCYP21). Intra-adrenal injection of hAdCYP21 in 21OH- mice induced hCYP21 mRNA with the highest expression from 2 to 7 days before a gradual decline. 21OH activity measured in adrenal tissue increased from undetectable to levels found in wild-type mice 2 to 7 days after AdhCYP21 injection. Adrenal morphology of 21OH- mice showed lack of zonation, and hypertrophy and hyperplasia of adrenocortical mitochondria with few tubulovesicular christae. These morphological abnormalities were markedly improved 7 days after hAdCYP21 gene therapy. Plasma corticosterone increased from undetectable levels to values similar in wild-type mice by 7 and 14 days, declining over the next 40 days. This is the first demonstration that a single intra-adrenal injection of an adenoviral vector encoding CYP21 can compensate for the biochemical, endocrine and histological alterations in 21OH-deficient mice, and shows that gene therapy could be a feasible option for treatment of CAH. JF - Gene Therapy AU - Tajima, T AU - Okada, T AU - Ma, X-M AU - Ramsey, W J AU - Bornstein AU - Aguilera, G AD - Section on Endocrine Physiology, Developmental Endocrinology Branch, NICHD, NIH, Bldg 10 Rm 10n262, 10 Center Drive MSC 1862, Bethesda, MD 20892-1862, USA Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 1898 EP - 1903 VL - 6 IS - 11 SN - 0969-7128, 0969-7128 KW - mice KW - man KW - CYP21 gene KW - congenital adrenal hyperplasia KW - cytochrome P450 21-hydroxylase KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Adrenal glands KW - Gene therapy KW - Gene transfer KW - Cytochrome P450 KW - Steroidogenesis KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17444941?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Restoration+of+adrenal+steroidogenesis+by+adenovirus-mediated+transfer+of+human+cytochrome+P450+21-hydroxylase+into+the+adrenal+gland+of+21-hydroxylase-deficient+mice&rft.au=Tajima%2C+T%3BOkada%2C+T%3BMa%2C+X-M%3BRamsey%2C+W+J%3BBornstein%3BAguilera%2C+G&rft.aulast=Tajima&rft.aufirst=T&rft.date=1999-11-01&rft.volume=6&rft.issue=11&rft.spage=1898&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytochrome P450; Steroidogenesis; Adrenal glands; Gene therapy; Gene transfer ER - TY - JOUR T1 - ClpA and ClpP Remain Associated during Multiple Rounds of ATP-Dependent Protein Degradation by ClpAP Protease AN - 17438554; 4654572 AB - The Escherichia coli ClpA and ClpP proteins form a complex, ClpAP, that catalyzes ATP-dependent degradation of proteins. Formation of stable ClpA hexamers and stable ClpAP complexes requires binding of ATP or nonhydrolyzable ATP analogues to ClpA. To understand the order of events during substrate binding, unfolding, and degradation by ClpAP, it is essential to know the oligomeric state of the enzyme during multiple catalytic cycles. Using inactive forms of ClpA or ClpP as traps for dissociated species, we measured the rates of dissociation of ClpA hexamers or ClpAP complexes. When ATP was saturating, the rate constant for dissociation of ClpA hexamers was 0.032 min super(-1) (t sub( one half ) of 22 min) at 37 degree C, and dissociation of ClpP from the ClpAP complexes occurred with a rate constant of 0.092 min super(-1) (t sub( one half ) of 7.5 min). Because the k sub(cat) for casein degradation is similar to 10 min super(-1), these results indicate that tens of molecules of casein can be turned over by the ClpAP complex before significant dissociation occurs. Mutations in the N-terminal ATP binding site led to faster rates of ClpA and ClpAP dissociation, whereas mutations in the C-terminal ATP binding site, which cause significant decreases in ATPase activity, led to lower rates of dissociation of ClpA and ClpAP complexes. Dissociation rates for wild-type and first domain mutants of ClpA were faster at low nucleotide concentrations. The t sub( one half ) for dissociation of ClpAP complexes in the presence of nonhydrolyzable analogues was greater than or equal to 30 min. Thus, ATP binding stabilizes the oligomeric state of ClpA, and cycles of ATP hydrolysis affect the dynamics of oligomer interaction. However, since the k sub(cat) for ATP hydrolysis is similar to 140 min super(-1), ClpA and the ClpAP complex remain associated during hundreds of rounds of ATP hydrolysis. Our results indicate that the ClpAP complex is the functional form of the protease and as such engages in multiple rounds of interaction with substrate proteins, degradation, and release of peptide products without dissociation. JF - Biochemistry (Washington) AU - Singh, S K AU - Guo, Fusheng AU - Maurizi, M R AD - National Cancer Institute, Building 37, Room 1B09, Bethesda, MD 20892-4255, USA, mmaurizi@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 14906 EP - 14915 VL - 38 IS - 45 SN - 0006-2960, 0006-2960 KW - dissociation KW - degradation KW - ClpA protein KW - ClpP protein KW - Microbiology Abstracts B: Bacteriology KW - Adenosinetriphosphatase KW - Escherichia coli KW - ATP KW - Hydrolysis KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17438554?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=ClpA+and+ClpP+Remain+Associated+during+Multiple+Rounds+of+ATP-Dependent+Protein+Degradation+by+ClpAP+Protease&rft.au=Singh%2C+S+K%3BGuo%2C+Fusheng%3BMaurizi%2C+M+R&rft.aulast=Singh&rft.aufirst=S&rft.date=1999-11-01&rft.volume=38&rft.issue=45&rft.spage=14906&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/10.1021%2Fbi991615f LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Adenosinetriphosphatase; ATP; Hydrolysis DO - http://dx.doi.org/10.1021/bi991615f ER - TY - JOUR T1 - A specialized version of the HD hydrolase domain implicated in signal transduction AN - 17432163; 4652905 AB - Recently, a superfamily of proteins containing a previously undetected domain with predicted metal-dependent phosphohydrolase activity has been described and designated the HD superfamily, after the principal conserved residues implicated in catalysis (Aravind and Koonin, 1998). In the course of our analysis of ancient conserved regions in microbial genomes (Koonin et al., 1998), we found a distinct version of this domain which is encoded in one to three copies in the genomes of Aquifex aeolicus, Borrelia burgdorferi, Synechocystis sp. and Treponema pallidum, but is dramatically expanded in the genomes of Thermotoga maritima and Clostridium acetobutylicum. Compared with the consensus HD domain (Aravind and Koonin, 1998), this version contains a number of additional highly conserved residues; hereinafter we refer to it as the HD-GYP domain, after the characteristic sequence signatures. This domain was also detected in previously uncharacterized proteins from Wolinella succinogenes (Kreis-Kleinschmidt et al., 1995), Bacillus halodurans (Takami et al., 1999), Pseudomonas aeruginosa and Bordetella pertussis. The HD-GYP domain is missing in E. coli and B. subtilis. Remarkably, however, in other gamma -proteobacteria, such as Shewanella putrefaciens and Vibrio cholerae, it is present in up to 8 copies (data not shown). While none of the proteins that contain the HD-GYP domain has ever been characterized experimentally, the spectrum of the domains that are associated with HD-GYP in multidomain proteins suggests that it is probably involved in signal transduction. JF - Journal of Molecular Microbiology and Biotechnology AU - Galperin, MY AU - Natale, DA AU - Aravind, L AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA, galperin@ncbi.nlm.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 303 EP - 305 VL - 1 IS - 2 SN - 1464-1801, 1464-1801 KW - HD Hydrolase KW - ASFA 1: Biological Sciences & Living Resources; Microbiology Abstracts B: Bacteriology KW - Molecular structure KW - Genomes KW - Phylogeny KW - Synechocystis KW - Borrelia burgdorferi KW - Enzymes KW - Wolinella succinogenes KW - Domains KW - Freshwater KW - Bordetella pertussis KW - Copy number control KW - Aquifex aeolicus KW - Treponema pallidum KW - Clostridium acetobutylicum KW - Proteins KW - Bacillus halodurans KW - Pseudomonas aeruginosa KW - Thermotoga maritima KW - Evolution KW - Signal transduction KW - Q1 08206:Physiology, biochemistry, biophysics KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17432163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.atitle=A+specialized+version+of+the+HD+hydrolase+domain+implicated+in+signal+transduction&rft.au=Galperin%2C+MY%3BNatale%2C+DA%3BAravind%2C+L%3BKoonin%2C+E+V&rft.aulast=Galperin&rft.aufirst=MY&rft.date=1999-11-01&rft.volume=1&rft.issue=2&rft.spage=303&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Microbiology+and+Biotechnology&rft.issn=14641801&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Phylogeny; Genomes; Molecular structure; Proteins; Enzymes; Evolution; Copy number control; Domains; Signal transduction; Synechocystis; Bordetella pertussis; Borrelia burgdorferi; Treponema pallidum; Aquifex aeolicus; Clostridium acetobutylicum; Bacillus halodurans; Wolinella succinogenes; Pseudomonas aeruginosa; Thermotoga maritima; Freshwater ER - TY - JOUR T1 - Tumour immunotherapy: developments and strategies AN - 17403758; 4631187 AB - Antitumour immune responses are generated by the complex interaction of cytotoxic T lymphocytes, T helper cells and antigen-presenting cells. An international meeting discussed progress in identification of tumour-associated antigens, tumour immunotherapy and understanding the mechanisms of tumour immunity. JF - Immunology Today AU - Chattopadhyay, U AD - Dept of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37 SP Mukherjee Road, Calcutta 700 026, India, cncinst@giascl01.vsnl.net.in Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 480 EP - 482 VL - 20 IS - 11 SN - 0167-5699, 0167-5699 KW - immunology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Helper cells KW - Immunotherapy KW - Tumors KW - Cancer KW - Reviews KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Vaccines KW - Antigen-presenting cells KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17403758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology+Today&rft.atitle=Tumour+immunotherapy%3A+developments+and+strategies&rft.au=Chattopadhyay%2C+U&rft.aulast=Chattopadhyay&rft.aufirst=U&rft.date=1999-11-01&rft.volume=20&rft.issue=11&rft.spage=480&rft.isbn=&rft.btitle=&rft.title=Immunology+Today&rft.issn=01675699&rft_id=info:doi/10.1016%2FS0167-5699%2899%2901526-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immunotherapy; Tumors; Reviews; Lymphocytes T; Helper cells; Antigen-presenting cells; Vaccines; Antigen (tumor-associated); Cancer DO - http://dx.doi.org/10.1016/S0167-5699(99)01526-1 ER - TY - JOUR T1 - The Bacteriophage P1 HumD Protein Is a Functional Homolog of the Prokaryotic UmuD'-Like Proteins and Facilitates SOS Mutagenesis in Escherichia coli AN - 17401955; 4627009 AB - The Escherichia coli umuD and umuC genes comprise an operon and encode proteins that are involved in the mutagenic bypass of normally replication- inhibiting DNA lesions. UmuD is, however, unable to function in this process until it undergoes a RecA-mediated cleavage reaction to generate UmuD'. Many homologs of umuDC have now been identified. Most are located on bacterial chromosomes or on broad-host-range R plasmids. One such putative homolog, humD (homolog of umuD) is however, found on the bacteriophage P1 genome. Interestingly humD differs from other umuD homologs in that it encodes a protein similar in size to the posttranslationally generated UmuD' protein and not UmuD, nor is it in an operon with a cognate umuC partner. To determine if HumD is, in fact, a bona fide homolog of the prokaryotic UmuD'-like mutagenesis proteins, we have analyzed the ability of HumD to complement UmuD' functions in vivo as well as examined HumD's physical properties in vitro. When expressed from a high-copy-number plasmid, HumD restored cellular mutagenesis and increased UV survival to normally nonmutable recA430 lexA(Def) and UV- sensitive Delta umuDC recA718 lexA(Def) strains, respectively. Complementing activity was reduced when HumD was expressed from a low-copy-number plasmid, but this observation is explained by immunoanalysis which indicates that HumD is normally poorly expressed in vivo. In vitro analysis revealed that like UmuD', HumD forms a stable dimer in solution and is able to interact with E. coli UmuC and RecA nucleoprotein filaments. We conclude, therefore, that bacteriophage P1 HumD is a functional homolog of the UmuD'-like proteins, and we speculate as to the reasons why P1 might require the activity of such a protein in vivo. JF - Journal of Bacteriology AU - McLenigan, M P AU - Kulaeva, OI AU - Ennis, D G AU - Levine, A S AU - Woodgate, R AD - Building 6, Room 1A13, NICHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892-2725, woodgate@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 7005 EP - 7013 VL - 181 IS - 22 SN - 0021-9193, 0021-9193 KW - HumD protein KW - RecA protein KW - UmuC protein KW - UmuD' protein KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts KW - Plasmids KW - Gene expression KW - Dimers KW - Escherichia coli KW - Mutation KW - Phage P1 KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17401955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+Bacteriophage+P1+HumD+Protein+Is+a+Functional+Homolog+of+the+Prokaryotic+UmuD%27-Like+Proteins+and+Facilitates+SOS+Mutagenesis+in+Escherichia+coli&rft.au=McLenigan%2C+M+P%3BKulaeva%2C+OI%3BEnnis%2C+D+G%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=McLenigan&rft.aufirst=M&rft.date=1999-11-01&rft.volume=181&rft.issue=22&rft.spage=7005&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage P1; Escherichia coli; Plasmids; Gene expression; Mutation; Dimers ER - TY - JOUR T1 - Syntheses and immunologic properties of Escherichia coli O157 O-specific polysaccharide and Shiga toxin 1 B subunit conjugates in mice AN - 17400404; 4629460 AB - Escherichia coli O157 is the major cause of diarrhea-associated hemolytic uremic syndrome (HUS). Strains causing HUS contain either Shiga toxin 1 (Stx1) or Stx2, or both. In adult volunteers, conjugate vaccines of detoxified lipopolysaccharide (LPS) elicited bactericidal antibodies to E. coli O157. Here, the detoxified LPS was conjugated with improved schemes to the nontoxic B subunit of Stx1. Mice injected with these bivalent conjugates elicited both bactericidal antibodies to E. coli O157 and neutralization antibodies to Stx1. JF - Infection and Immunity AU - Konadu, E AU - Donohue-Rolfe, A AU - Calderwood, S B AU - Pozsgay, V AU - Shiloach, J AU - Robbins, J B AU - Szu, S C AD - National Institute of Child Health and Human Development, Room 424, Building 6, National Institutes of Health, Bethesda, MD 20892-2720, USA, scszu@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 6191 EP - 6193 VL - 67 IS - 11 SN - 0019-9567, 0019-9567 KW - mice KW - immunology KW - Escherichia coli KW - Shiga toxin KW - Shiga toxin 1 KW - lipopolysaccharides KW - polysaccharides KW - Immunology Abstracts; Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Hemolytic uremic syndrome KW - Lipopolysaccharides KW - Vaccines KW - Antibody response KW - Conjugates KW - Immunization KW - J 02834:Vaccination and immunization KW - X 24171:Microbial KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17400404?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Syntheses+and+immunologic+properties+of+Escherichia+coli+O157+O-specific+polysaccharide+and+Shiga+toxin+1+B+subunit+conjugates+in+mice&rft.au=Konadu%2C+E%3BDonohue-Rolfe%2C+A%3BCalderwood%2C+S+B%3BPozsgay%2C+V%3BShiloach%2C+J%3BRobbins%2C+J+B%3BSzu%2C+S+C&rft.aulast=Konadu&rft.aufirst=E&rft.date=1999-11-01&rft.volume=67&rft.issue=11&rft.spage=6191&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Hemolytic uremic syndrome; Antibody response; Lipopolysaccharides; Vaccines; Conjugates; Immunization ER - TY - JOUR T1 - Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam AN - 17399616; 4629451 AB - The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA sub(1)) or adipic acid dihydrazide (ADH; Vi-rEPA sub(2)) as linkers. None of the recipients experienced a temperature of >38.5 degree C or significant local reactions. One injection of Vi-rEPA sub(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA sub(2), Vi-rEPA sub(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA sub(1) and Vi with respect to Vi-rEPA sub(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA sub(2), Vi-rEPA sub(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA sub(1) and Vi with respect to Vi-rEPA sub(2)); all were higher than the preinjection levels (P = 0.0001). Vi-rEPA sub(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA sub(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA sub(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA sub(2) and from 28.9 to 83.0 EU for Vi-rEPA sub(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA sub(2) and 12.8 versus 0.33 for Vi-rEPA sub(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA sub(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA sub(2) conjugate warrant further investigation. JF - Infection and Immunity AU - Kossaczka, Z AU - Lin, F-YC AU - Ho, V A AU - Thuy, NTT AU - Bay, P V AU - Thanh, T C AU - Khiem, H B AU - Trach, D D AU - Karpas, A AU - Hunt, S AU - Bryla, DA AU - Schneerson, R AU - Robbins, J B AU - Szu, S C AD - National Institutes of Health, Bethesda, MD 20892, USA, scszu@helix.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 5806 EP - 5810 VL - 67 IS - 11 SN - 0019-9567, 0019-9567 KW - man KW - immunology KW - adults KW - Adipic acid dihydrazide KW - N-Succinimidyl-3-(2-pyridyldithio)-propionate KW - Pseudomonas aeruginosa KW - RepA protein KW - Vi antigen KW - Vietnam KW - double prime Vi antigen KW - exoprotein A KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - ^AVi antigen KW - Salmonella typhi KW - Antibody response KW - Vaccines KW - Children KW - Polysaccharides KW - Conjugates KW - Typhoid fever KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17399616?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Safety+and+immunogenicity+of+Vi+conjugate+vaccines+for+typhoid+fever+in+adults%2C+teenagers%2C+and+2-+to+4-year-old+children+in+Vietnam&rft.au=Kossaczka%2C+Z%3BLin%2C+F-YC%3BHo%2C+V+A%3BThuy%2C+NTT%3BBay%2C+P+V%3BThanh%2C+T+C%3BKhiem%2C+H+B%3BTrach%2C+D+D%3BKarpas%2C+A%3BHunt%2C+S%3BBryla%2C+DA%3BSchneerson%2C+R%3BRobbins%2C+J+B%3BSzu%2C+S+C&rft.aulast=Kossaczka&rft.aufirst=Z&rft.date=1999-11-01&rft.volume=67&rft.issue=11&rft.spage=5806&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhi; Pseudomonas aeruginosa; Vaccines; Typhoid fever; Conjugates; Antibody response; Polysaccharides; Children ER - TY - JOUR T1 - Human onchocerciasis and tetanus vaccination: Impact on the postvaccination antitetanus antibody response AN - 17396923; 4629439 AB - To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses. JF - Infection and Immunity AU - Cooper, P J AU - Espinel, I AU - Wieseman, M AU - Paredes, W AU - Espinel, M AU - Guderian, R H AU - Nutman, T B AD - Laboratory of Parasitic Diseases, NIAID, Bldg. 4, Rm. 126, National Institutes of Health, 4 Center Dr., Bethesda, MD 20892-0425, USA, pcooper@niaid.nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 5951 EP - 5957 VL - 67 IS - 11 SN - 0019-9567, 0019-9567 KW - man KW - immunology KW - Clostridium tetani KW - Onchocerca volvulus KW - Strongyloides stercoralis KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Concurrent infection KW - Immunoglobulin G KW - Vaccines KW - Antibody response KW - Tetanus KW - Vaccination KW - Immunoglobulins KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17396923?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Human+onchocerciasis+and+tetanus+vaccination%3A+Impact+on+the+postvaccination+antitetanus+antibody+response&rft.au=Cooper%2C+P+J%3BEspinel%2C+I%3BWieseman%2C+M%3BParedes%2C+W%3BEspinel%2C+M%3BGuderian%2C+R+H%3BNutman%2C+T+B&rft.aulast=Cooper&rft.aufirst=P&rft.date=1999-11-01&rft.volume=67&rft.issue=11&rft.spage=5951&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Onchocerca volvulus; Strongyloides stercoralis; Tetanus; Antibody response; Immunoglobulin G; Vaccines; Vaccination; Immunoglobulins; Concurrent infection ER - TY - JOUR T1 - The right time and place for molecular scissors AN - 17351014; 4633204 AB - The development of genetic tools has been and will continue to be a driving force in biological discovery. In particular, the ability to mutate genes within the mouse genome has been instrumental in the identification and understanding of genetic pathways controlling organogenesis and tumorigenesis. Now, Wen-Hwa Lee and colleagues report experiments that take the application of molecular tools to new heights. They combined the generic Cre-loxP recombination system with a tetracycline-dependent switch and topped it off with tissue-specific control elements. This technical voyage will enable biologists to precisely manipulate individual genes in specific tissues and at predetermined time points. JF - Nature Biotechnology AU - Hennighausen, L AU - Furth, P A AD - Laboratory of Genetics and Physiology, National Institute of Health, Bldg. 8, Rm. 101, Bethesda, MD 20892, USA, mammary@nih.gov Y1 - 1999/11// PY - 1999 DA - Nov 1999 SP - 1062 EP - 1063 VL - 17 IS - 11 SN - 1087-0156, 1087-0156 KW - gene expression KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Transgenic mice KW - Promoters KW - Reviews KW - Cre recombinase KW - G 07397:Rodentia (mice) KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33055:Genetic engineering (general) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17351014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=The+right+time+and+place+for+molecular+scissors&rft.au=Hennighausen%2C+L%3BFurth%2C+P+A&rft.aulast=Hennighausen&rft.aufirst=L&rft.date=1999-11-01&rft.volume=17&rft.issue=11&rft.spage=1062&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/10.1038%2F15046 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Transgenic mice; Cre recombinase; Promoters DO - http://dx.doi.org/10.1038/15046 ER - TY - JOUR T1 - Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes. AN - 69342571; 10591488 AB - Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. In Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (< or =50 ppm) a clear dose-related increase in total proliferative lesions of the prostate (ventral and dorsolateral lesions combined) occurred (0 ppm = 21% incidence, 25 ppm = 46%, 50 ppm = 50%; trend p < .03). These lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells without stromal invasion. The lesions occurred primarily in the dorsolateral prostate with cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional cell), although few in number, showed a positive correlation with cadmium dose, as did pelvic transitional epithelial hyperplasia. Renal lesions were not associated with any cadmium-induced changes in age-related chronic nephropathy. The incidence of pheochromocytomas of the adrenal was increased by cadmium but only at the 50 ppm dose. Inflammatory lesions of the liver and spleen were common at higher doses and showed strong trends based on dose. These results indicate that oral cadmium can induce proliferative lesions in the prostate and kidney of the Noble rat. The finding of proliferative lesions of dorsolateral prostate in rats has presumed relevance to human prostate cancers. JF - Journal of toxicology and environmental health. Part A AU - Waalkes, M P AU - Anver, M R AU - Diwan, B A AD - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. waalkes.NIEHS.NIH.gov. Y1 - 1999/10/29/ PY - 1999 DA - 1999 Oct 29 SP - 199 EP - 214 VL - 58 IS - 4 SN - 1528-7394, 1528-7394 KW - Carcinogens KW - 0 KW - Cadmium KW - 00BH33GNGH KW - Index Medicus KW - Rats, Inbred Strains KW - Rats KW - Hyperplasia -- pathology KW - Animals KW - Hyperplasia -- chemically induced KW - Pheochromocytoma -- chemically induced KW - Chemical and Drug Induced Liver Injury -- pathology KW - Carcinogenicity Tests KW - Splenic Diseases -- pathology KW - Pheochromocytoma -- pathology KW - Splenic Diseases -- chemically induced KW - Male KW - Prostatic Neoplasms -- pathology KW - Kidney Neoplasms -- pathology KW - Prostatic Hyperplasia -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Testicular Neoplasms -- pathology KW - Prostatic Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Cadmium -- toxicity KW - Adrenal Gland Neoplasms -- chemically induced KW - Adrenal Gland Neoplasms -- pathology KW - Prostatic Hyperplasia -- pathology KW - Testicular Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69342571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Chronic+toxic+and+carcinogenic+effects+of+oral+cadmium+in+the+Noble+%28NBL%2FCr%29+rat%3A+induction+of+neoplastic+and+proliferative+lesions+of+the+adrenal%2C+kidney%2C+prostate%2C+and+testes.&rft.au=Waalkes%2C+M+P%3BAnver%2C+M+R%3BDiwan%2C+B+A&rft.aulast=Waalkes&rft.aufirst=M&rft.date=1999-10-29&rft.volume=58&rft.issue=4&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-22 N1 - Date created - 1999-12-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell proliferation. AN - 69206566; 10531310 AB - The insulin receptor substrates (IRSs)-1-4 play important roles in signal transduction emanating from the insulin and insulin-like growth factor (IGF)-I receptors. IRS-4 is the most recently characterized member, which has been found primarily in human cells and tissues. It interacts with SH2-containing proteins such as phosphatidylinositol 3'-kinase (PI3K), Grb2, Crk-II, and CrkL. In this study, we transfected IRS-4 in mouse NIH-3T3 cells that overexpress IGF-I receptors. Clones expressing IRS-4 showed enhanced cellular proliferation when cells were cultured in 1% fetal bovine serum without added IGF-I. Addition of IGF-I enhanced cellular proliferation in cells overexpressing the IGF-I receptor alone but had an even greater proliferative effect in cells overexpressing both the IGF-I receptors and IRS-4. When etoposide and methylmethane sulfonate (MMS), both DNA damaging agents, were added to the cells, they uniformly induced cell cycle arrest. Fluorescence-activated cell sorter analysis demonstrated that the arrest of the cell cycle occurred at the G(1) checkpoint, and furthermore no significant degree of apoptosis was demonstrated with the use of either agent. In cells, overexpressing IGF-I receptors alone, IGF-I addition enhanced cellular proliferation, even in the presence of etoposide and MMS. In cells overexpressing IGF-I receptors and IRS-4, the effect of IGF-I in overcoming the cell cycle arrest was even more pronounced. These results suggest that IRS-4 is implicated in the IGF-I receptor mitogenic signaling pathway. JF - The Journal of biological chemistry AU - Qu, B H AU - Karas, M AU - Koval, A AU - LeRoith, D AD - Section on Molecular Physiology, CEB/NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1758, USA. Y1 - 1999/10/29/ PY - 1999 DA - 1999 Oct 29 SP - 31179 EP - 31184 VL - 274 IS - 44 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Growth Inhibitors KW - IRS4 protein, human KW - Insulin Receptor Substrate Proteins KW - Irs4 protein, mouse KW - Mitogens KW - Phosphoproteins KW - Insulin-Like Growth Factor I KW - 67763-96-6 KW - Etoposide KW - 6PLQ3CP4P3 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Receptor, IGF Type 1 KW - EC 2.7.10.1 KW - Index Medicus KW - Mitogens -- pharmacology KW - Etoposide -- pharmacology KW - Animals KW - 3T3 Cells KW - Humans KW - Growth Inhibitors -- pharmacology KW - Mice KW - Signal Transduction KW - Methyl Methanesulfonate -- pharmacology KW - Phosphoproteins -- genetics KW - Receptor, IGF Type 1 -- metabolism KW - Cell Division -- physiology KW - Receptor, IGF Type 1 -- genetics KW - Insulin-Like Growth Factor I -- pharmacology KW - Phosphoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69206566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Insulin+receptor+substrate-4+enhances+insulin-like+growth+factor-I-induced+cell+proliferation.&rft.au=Qu%2C+B+H%3BKaras%2C+M%3BKoval%2C+A%3BLeRoith%2C+D&rft.aulast=Qu&rft.aufirst=B&rft.date=1999-10-29&rft.volume=274&rft.issue=44&rft.spage=31179&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-16 N1 - Date created - 1999-12-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Catalytic Mechanism of the Tryptophan Synthase alpha sub(2) beta sub(2) Complex: Effects of pH, isotopic substitution, and allosteric ligands AN - 17458055; 4668316 AB - The mechanism of the tryptophan synthase alpha sub(2) beta sub(2) complex from Salmonella typhimurium is explored by determining the effects of pH, of temperature, and of isotopic substitution on the pyridoxal phosphate-dependent reaction of L-serine with indole to form L-tryptophan. The pH dependence of the kinetic parameters indicates that three ionizing groups are involved in substrate binding and catalysis with pKa1 = 6.5, pKa2 = 7.3, and pKa3 = 8.2-9. A significant primary isotope effect (~3.5) on V and V/K is observed at low pH (pH 7), but not at high pH (pH 9), indicating that the base that accepts the alpha -proton ( beta Lys-87) is protonated at low pH, slowing the abstraction of the alpha -proton and making this step at least partially rate-limiting. pKa2 is assigned to beta Lys-87 on the basis of the kinetic isotope effect results and of the observation that the competitive inhibitors glycine and oxindolyl-L-alanine display single pKi values of 7.3. The residue with this pKa ( beta Lys-87) must be unprotonated for binding glycine or oxindolyl-L-alanine, and, by inference, L-serine. Investigations of the temperature dependence of the pKa values support the assignment of pKa2 to beta Lys-87 and suggest that the ionizing residue with pKa1 could be a carboxylate, possibly beta Asp-305, and that the residue associated with a conformational change at pKa3 may be beta Lys-167. The occurrence of a closed to open conformational conversion at high pH is supported by investigations of the effects of pH on reaction specificity and on the equilibrium distribution of enzyme-substrate intermediates. JF - Journal of Biological Chemistry AU - Ro, H AU - Miles, E W AD - Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892- 0830 Y1 - 1999/10/29/ PY - 1999 DA - 1999 Oct 29 SP - 31189 EP - 31194 VL - 274 IS - 44 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology KW - Salmonella typhimurium KW - pH effects KW - Tryptophan synthase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17458055?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Catalytic+Mechanism+of+the+Tryptophan+Synthase+alpha+sub%282%29+beta+sub%282%29+Complex%3A+Effects+of+pH%2C+isotopic+substitution%2C+and+allosteric+ligands&rft.au=Ro%2C+H%3BMiles%2C+E+W&rft.aulast=Ro&rft.aufirst=H&rft.date=1999-10-29&rft.volume=274&rft.issue=44&rft.spage=31189&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/10.1074%2Fjbc.274.44.31189 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Salmonella typhimurium; Tryptophan synthase; pH effects DO - http://dx.doi.org/10.1074/jbc.274.44.31189 ER - TY - JOUR T1 - Activation of the cholesterol pathway and Ras maturation in response to stress. AN - 69276390; 10557091 AB - All cells depend on sterols and isoprenoids derived from mevalonate (MVA) for growth, differentiation, and maintenance of homeostatic functions. In plants, environmental insults like heat and sunlight trigger the synthesis of isoprene, also derived from MVA, and this phenomenon has been associated with enhanced tolerance to heat. Here, we show that in human prostate adenocarcinoma PC-3M cells heat shock leads to activation of the MVA pathway. This is characterized by a dose- and time-dependent elevation in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) activity, enhanced sterol and isoprenoid synthesis, and increased protein prenylation. Furthermore, prenylation and subsequent membrane localization of Ras, a central player in cell signaling, was rapidly induced following heat stress. These effects were dose-dependent, augmented with repeated insults, and were prevented by culturing cells in the presence of lovastatin, a competitive inhibitor of HMGR. Enhanced Ras maturation by heat stress was also associated with a heightened activation of extracellular signal-regulated kinase (ERK), a key mediator of both mitogenic and stress signaling pathways, in response to subsequent growth factor stimulation. Thus, activation of the MVA pathway may constitute an important adaptive host response to stress, and have significant implications to carcinogenesis. JF - Oncogene AU - Shack, S AU - Gorospe, M AU - Fawcett, T W AU - Hudgins, W R AU - Holbrook, N J AD - Cell Stress and Aging Section, Laboratory of Biological Chemistry, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, Maryland, MD 21224, USA. Y1 - 1999/10/28/ PY - 1999 DA - 1999 Oct 28 SP - 6021 EP - 6028 VL - 18 IS - 44 SN - 0950-9232, 0950-9232 KW - Diterpenes KW - 0 KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors KW - Sterols KW - Farnesol KW - 4602-84-0 KW - Cholesterol KW - 97C5T2UQ7J KW - Lovastatin KW - 9LHU78OQFD KW - geranylgeraniol KW - AIA02AJA3A KW - Hydroxymethylglutaryl CoA Reductases KW - EC 1.1.1.- KW - Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent KW - EC 1.1.1.34 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Mitogen-Activated Protein Kinase 1 KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 3 KW - Mitogen-Activated Protein Kinases KW - ras Proteins KW - EC 3.6.5.2 KW - Mevalonic Acid KW - S5UOB36OCZ KW - Index Medicus KW - ras Proteins -- genetics KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors -- pharmacology KW - Mitogen-Activated Protein Kinases -- metabolism KW - Humans KW - Sterols -- biosynthesis KW - Lovastatin -- pharmacology KW - Diterpenes -- metabolism KW - Protein Prenylation KW - Mevalonic Acid -- metabolism KW - ras Proteins -- metabolism KW - Farnesol -- metabolism KW - Male KW - Heat-Shock Response -- genetics KW - Prostatic Neoplasms -- metabolism KW - Prostatic Neoplasms -- etiology KW - Genes, ras KW - Stress, Physiological -- complications KW - Adenocarcinoma -- metabolism KW - Stress, Physiological -- metabolism KW - Cholesterol -- metabolism KW - Adenocarcinoma -- etiology KW - Prostatic Neoplasms -- drug therapy KW - Hydroxymethylglutaryl CoA Reductases -- metabolism KW - Adenocarcinoma -- drug therapy KW - Hydroxymethylglutaryl CoA Reductases -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69276390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Activation+of+the+cholesterol+pathway+and+Ras+maturation+in+response+to+stress.&rft.au=Shack%2C+S%3BGorospe%2C+M%3BFawcett%2C+T+W%3BHudgins%2C+W+R%3BHolbrook%2C+N+J&rft.aulast=Shack&rft.aufirst=S&rft.date=1999-10-28&rft.volume=18&rft.issue=44&rft.spage=6021&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-03 N1 - Date created - 1999-12-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of transfusion-associated transmission of human herpesvirus 8 AN - 17430978; 4636298 AB - Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma herpesvirus, causes Kaposi's sarcoma and is associated with body cavity-based lymphomas and multicentric Castleman's disease. HHV8 is spread sexually, but other routes of transmission probably exist because, in some cases, infection has been shown to be acquired in childhood in HHV8-endemic areas, such as Mediterranean Europe and sub-Saharan Africa. An unresolved question with public health implications is whether blood transfusions can transmit HHV8. HHV8 can be identified in circulating lymphocytes from healthy blood donors, although the proportion of infected donors with viremia is unknown. Cytomegalovirus, another cell-associated herpesvirus, is readily transmitted via blood transfusion, and both HHV8 and cytomegalovirus are transmitted through solid organ transplantation. However, no study to date has documented HHV8 transmission through transfusion; the only study to examine this question directly found no transmission of HHV8 from 14 HHV8-seropositive donors. Furthermore, HHV8 infection is relatively rare in frequently transfused groups, such as hemophiliacs and thalassemia or sickle cell anemia patients. Determining whether transfusions may transmit HHV8 has been difficult because HHV8 infection is fairly uncommon among many donor populations [e.g., 0%-5% seroprevalence in the United States, in the U.K., and in the Caribbean]. To determine whether blood transfusions can transmit HHV8, we evaluated individuals in the Jamaica Transfusion Study. JF - Journal of the National Cancer Institute AU - Engels, E A AU - Eastman, H AU - Ablashi, D V AU - Wilks, R J AU - Braham, J AU - Manns, A AD - National Institutes of Health, 6120 Executive Blvd., MSC 7248, Bethesda, MD 20822, engelse@exchange.nih.gov Y1 - 1999/10/20/ PY - 1999 DA - 1999 Oct 20 VL - 91 IS - 20 SN - 0027-8874, 0027-8874 KW - Human herpesvirus 8 KW - Kaposi's sarcoma KW - blood transfusion KW - Risk Abstracts; Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Blood transfusion KW - Epidemiology KW - Kaposi's sarcoma-associated herpesvirus KW - H 13000:Medical Safety KW - R2 23060:Medical and environmental health KW - V 22114:Human oncogenic viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17430978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Risk+of+transfusion-associated+transmission+of+human+herpesvirus+8&rft.au=Engels%2C+E+A%3BEastman%2C+H%3BAblashi%2C+D+V%3BWilks%2C+R+J%3BBraham%2C+J%3BManns%2C+A&rft.aulast=Engels&rft.aufirst=E&rft.date=1999-10-20&rft.volume=91&rft.issue=20&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human herpesvirus 8; Kaposi's sarcoma-associated herpesvirus; Blood transfusion; Kaposi's sarcoma; Epidemiology ER - TY - JOUR T1 - Tumor-specific gene delivery using recombinant vaccinia virus in a rabbit model of liver metastases AN - 17423011; 4636295 AB - Several approaches to gene therapy for cancer have yielded promising results in rodent models. The translation of these results to the clinical realm has been delayed by the lack of tumor models in large animals. We investigated the pattern of transgene (i.e., foreign or introduced gene) expression and virus vector elimination after systemic gene delivery using a thymidine kinase-negative vaccinia virus in a rabbit model of disseminated liver metastases. VX-2 rabbit carcinoma cells were maintained by serial transplantation in the thigh muscles of New Zealand White rabbits, and disseminated liver metastases were established by direct injection of tumor cells into the portal vein of the animals. Different doses of a recombinant thymidine kinase-negative vaccinia virus vector encoding the firefly luciferase reporter gene (i.e., transgene) were injected into tumor-bearing rabbits. Transgene activity in tumors and other organs was measured at multiple time points thereafter. The pattern of development of antibodies against the vaccinia virus vector was also examined. Two-tailed Student's paired t test was used for comparisons of transgene activity. Transgene expression was increased in tumors by at least 16-fold in comparison with expression in other tissues by day 4 after vector injection (all P.001) and was maintained for approximately 1 week, providing evidence of tumor-specific gene delivery in this model. Rapid elimination of the circulating vector by the host immune system was observed. Anti-vector antibodies were detectable in serum as early as day 6 and were maintained for more than 3 months. Tumor-specific gene delivery is possible after systemic injection of a thymidine kinase-negative vaccinia virus vector in a model of rabbit liver metastases. Although the period of transgene expression appears limited because of a rapid immune response, the therapeutic window might be sufficient for an enzyme/prodrug gene therapy approach in clinical application. JF - Journal of the National Cancer Institute AU - Gnant, MFX AU - Noll, LA AU - Irvine, K R AU - Puhlmann, M AU - Terrill, R E AU - Alexander, HR Jr AU - Bartlett, D L AD - National Institutes of Health, Bldg. 10, Rm. 2B07, Bethesda, MD 20892, dbart@nih.gov Y1 - 1999/10/20/ PY - 1999 DA - 1999 Oct 20 SP - 1744 EP - 1750 VL - 91 IS - 20 SN - 0027-8874, 0027-8874 KW - rabbits KW - animal models KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Metastases KW - Gene therapy KW - Gene transfer KW - Liver KW - Carcinoma KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17423011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Tumor-specific+gene+delivery+using+recombinant+vaccinia+virus+in+a+rabbit+model+of+liver+metastases&rft.au=Gnant%2C+MFX%3BNoll%2C+LA%3BIrvine%2C+K+R%3BPuhlmann%2C+M%3BTerrill%2C+R+E%3BAlexander%2C+HR+Jr%3BBartlett%2C+D+L&rft.aulast=Gnant&rft.aufirst=MFX&rft.date=1999-10-20&rft.volume=91&rft.issue=20&rft.spage=1744&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Metastases; Gene transfer; Carcinoma; Gene therapy ER - TY - JOUR T1 - The base substitution fidelity of HIV-1 reverse transcriptase on DNA and RNA templates probed with 8-oxo-deoxyguanosine triphosphate. AN - 70845336; 10526200 AB - We have used 8-O-dGTP, a mutagenic nucleotide generated by oxidative metabolism, to probe the misincorporation potential of HIV-1 reverse transcriptase (RT) during DNA synthesis templated by the same nucleotide sequence as either RNA or DNA. With either template, 8-O-dGMP was misincorporated opposite template A, yielding characteristic A-->C transversions. The error rate with DNA was similar to that with RNA, suggesting that base misincorporation by the RT during first-strand and second-strand replication may contribute equally to the HIV-1 base substitution mutation rate. The rate of 8-O-dGMP misincorporation differed by more than 10-fold among the 20 adenines in the M13mp2 template where A-->C transversions can be detected. The transversion distribution was similar with the two templates, indicating that the effects of flanking nucleotides on misincorporation rates were similar. This is consistent with structural and biochemical data suggesting that HIV-1 RT binds RNA x DNA and DNA x DNA template-primers in the same orientation. The similarities in error rates and distribution further indicate that, despite differences in the structures of free RNA x DNA and DNA x DNA duplexes (e.g., minor groove dimensions), the polymerase active site that assembles upon substrate binding establishes a similar degree of nucleotide selectivity with both types of template-primers. Comparison of the RT error distribution to that observed with two Pol I family DNA polymerases and a Pol alpha family polymerase revealed common hot and cold spots for misincorporation. This suggests that the local nucleotide sequence influences the nucleotide selectivity of four polymerases in a similar manner, despite their differences in structure, biochemical properties, and functions. JF - Mutation research AU - Bebenek, K AU - Boyer, J C AU - Kunkel, T A AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA. Y1 - 1999/10/19/ PY - 1999 DA - 1999 Oct 19 SP - 149 EP - 158 VL - 429 IS - 2 SN - 0027-5107, 0027-5107 KW - Deoxyguanine Nucleotides KW - 0 KW - Nucleic Acid Heteroduplexes KW - Recombinant Proteins KW - 8-oxodeoxyguanosine triphosphate KW - 139307-94-1 KW - RNA KW - 63231-63-0 KW - DNA KW - 9007-49-2 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Models, Molecular KW - Humans KW - Base Pair Mismatch KW - Molecular Sequence Data KW - Templates, Genetic KW - Mutation KW - Binding Sites KW - HIV Reverse Transcriptase -- genetics KW - DNA -- genetics KW - HIV-1 -- enzymology KW - DNA -- biosynthesis KW - RNA -- genetics KW - RNA -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70845336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=The+base+substitution+fidelity+of+HIV-1+reverse+transcriptase+on+DNA+and+RNA+templates+probed+with+8-oxo-deoxyguanosine+triphosphate.&rft.au=Bebenek%2C+K%3BBoyer%2C+J+C%3BKunkel%2C+T+A&rft.aulast=Bebenek&rft.aufirst=K&rft.date=1999-10-19&rft.volume=429&rft.issue=2&rft.spage=149&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Substrate gating confers steroid specificity to estrogen sulfotransferase. AN - 70837236; 10514486 AB - Estrogen sulfotransferase (EST) exhibits a high substrate specificity and catalytic efficiency toward estrogens such as estradiol (E2) but insignificant ability to sulfate hydroxysteroids such as dehydroepiandrosterone (DHEA). To provide the structural basis for this estrogen specificity, we mutated amino acid residues that constitute the substrate-binding site of EST. Among these mutants, only Tyr-81 decreased E2 and increased DHEA sulfotransferase activities. Substitution for Tyr-81 by smaller hydrophobic residues increased K(m(E2)) for E2 activity, whereas the k(cat(E2)) remained relatively constant. The Y81L mutant exhibited the same DHEA activity as wild-type hydroxysteroid sulfotransferase, for which K(m(DHEA)) remained relatively constant, and k(cat(DHEA)) was markedly increased. The side chain of Tyr-81 is directed at the A-ring of the E2 molecule in the substrate-binding pocket of EST, constituting a steric gate with Phe-142 sandwiching E2 from the opposite side. The present mutagenesis study indicates that the 3beta-hydroxyl group of the DHEA molecule is excluded from the catalytic site of EST through steric hindrance of Tyr-81 with the C-19 methyl group of DHEA. Thus, this stricture-like gating caused by steric hindrance appears to be a structural principle for conferring estrogen specificity to EST. JF - The Journal of biological chemistry AU - Petrotchenko, E V AU - Doerflein, M E AU - Kakuta, Y AU - Pedersen, L C AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/10/15/ PY - 1999 DA - 1999 Oct 15 SP - 30019 EP - 30022 VL - 274 IS - 42 SN - 0021-9258, 0021-9258 KW - Estrogens KW - 0 KW - Recombinant Proteins KW - Dehydroepiandrosterone KW - 459AG36T1B KW - Sulfotransferases KW - EC 2.8.2.- KW - estrone sulfotransferase KW - EC 2.8.2.4 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Estrogens -- metabolism KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Escherichia coli -- genetics KW - Substrate Specificity KW - Dehydroepiandrosterone -- metabolism KW - Sulfotransferases -- genetics KW - Sulfotransferases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70837236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Substrate+gating+confers+steroid+specificity+to+estrogen+sulfotransferase.&rft.au=Petrotchenko%2C+E+V%3BDoerflein%2C+M+E%3BKakuta%2C+Y%3BPedersen%2C+L+C%3BNegishi%2C+M&rft.aulast=Petrotchenko&rft.aufirst=E&rft.date=1999-10-15&rft.volume=274&rft.issue=42&rft.spage=30019&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine. AN - 70832637; 10522644 AB - Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries. JF - Journal of toxicology and environmental health. Part A AU - Gladen, B C AU - Schecter, A J AU - Päpke, O AU - Shkyryak-Nyzhnyk, Z A AU - Hryhorczuk, D O AU - Little, R E AD - Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. gladen@niehs.nih.gov Y1 - 1999/10/15/ PY - 1999 DA - 1999 Oct 15 SP - 119 EP - 127 VL - 58 IS - 3 SN - 1528-7394, 1528-7394 KW - Benzofurans KW - 0 KW - Polychlorinated Dibenzodioxins KW - Polymers KW - polychlorodibenzofuran KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Humans KW - Ukraine KW - Adult KW - Longitudinal Studies KW - Female KW - Polychlorinated Dibenzodioxins -- analogs & derivatives KW - Polychlorinated Dibenzodioxins -- analysis KW - Milk, Human -- chemistry KW - Polychlorinated Biphenyls -- toxicity KW - Polychlorinated Dibenzodioxins -- toxicity KW - Polychlorinated Biphenyls -- analysis KW - Polymers -- analysis KW - Benzofurans -- analysis KW - Polymers -- toxicity KW - Benzofurans -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832637?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Polychlorinated+dibenzo-p-dioxins%2C+polychlorinated+dibenzofurans%2C+and+coplanar+polychlorinated+biphenyls+in+breast+milk+from+two+cities+in+Ukraine.&rft.au=Gladen%2C+B+C%3BSchecter%2C+A+J%3BP%C3%A4pke%2C+O%3BShkyryak-Nyzhnyk%2C+Z+A%3BHryhorczuk%2C+D+O%3BLittle%2C+R+E&rft.aulast=Gladen&rft.aufirst=B&rft.date=1999-10-15&rft.volume=58&rft.issue=3&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. AN - 70832334; 10521354 AB - Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that lead to cell death. Here, the isolation of the gene for an enzyme that can hydrolyze the bond between this protein and DNA is described. Enzyme-defective mutants of yeast are hypersensitive to treatments that increase the amount of covalent complexes, indicative of enzyme involvement in repair. The gene is conserved in eukaryotes and identifies a family of enzymes that has not been previously recognized. The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy. JF - Science (New York, N.Y.) AU - Pouliot, J J AU - Yao, K C AU - Robertson, C A AU - Nash, H A AD - Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B08, Bethesda, MD 20892-4034, USA. Y1 - 1999/10/15/ PY - 1999 DA - 1999 Oct 15 SP - 552 EP - 555 VL - 286 IS - 5439 SN - 0036-8075, 0036-8075 KW - DNA, Fungal KW - 0 KW - Phosphoric Diester Hydrolases KW - EC 3.1.4.- KW - TDP1 protein, human KW - tyrosyl-DNA phosphodiesterase KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Camptothecin KW - XT3Z54Z28A KW - Index Medicus KW - Animals KW - Sequence Alignment KW - Genes, Fungal KW - Camptothecin -- pharmacology KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutation KW - Expressed Sequence Tags KW - Saccharomyces cerevisiae -- genetics KW - Phosphoric Diester Hydrolases -- genetics KW - DNA Repair KW - Saccharomyces cerevisiae -- enzymology KW - Phosphoric Diester Hydrolases -- metabolism KW - DNA, Fungal -- metabolism KW - DNA Topoisomerases, Type I -- genetics KW - Saccharomyces cerevisiae -- drug effects KW - Phosphoric Diester Hydrolases -- chemistry KW - DNA Topoisomerases, Type I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70832334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28New+York%2C+N.Y.%29&rft.atitle=Yeast+gene+for+a+Tyr-DNA+phosphodiesterase+that+repairs+topoisomerase+I+complexes.&rft.au=Pouliot%2C+J+J%3BYao%2C+K+C%3BRobertson%2C+C+A%3BNash%2C+H+A&rft.aulast=Pouliot&rft.aufirst=J&rft.date=1999-10-15&rft.volume=286&rft.issue=5439&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=Science+%28New+York%2C+N.Y.%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-08 N1 - Date created - 1999-11-08 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF182002; GENBANK; AF182003 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IRB review of psychiatric medication discontinuation and symptom-provoking studies. AN - 69218458; 10536740 AB - Federal regulations governing human subjects research call for additional protections for the "mentally disabled." However, there is currently no consensus definition of mental disability or guidelines for how these research subjects should be protected. This ambiguity complicates the work of institutional review boards (IRBs) charged with the review and approval of protocols involving psychiatric medication discontinuation and symptom provocation. It is particularly important for these studies to be reviewed within the larger context of the research program in which they are conducted. The author proposes a process for IRB review of these studies, which includes the implementation of additional safeguards for subjects determined by the IRB to be vulnerable. Recommendations also are made for training psychiatric clinical investigators in issues related to research bioethics. JF - Biological psychiatry AU - Rosenstein, D L AD - National Institute of Mental Health, Bethesda MD 20892-1277, USA. Y1 - 1999/10/15/ PY - 1999 DA - 1999 Oct 15 SP - 1039 EP - 1043 VL - 46 IS - 8 SN - 0006-3223, 0006-3223 KW - Bioethics KW - Index Medicus KW - Biomedical and Behavioral Research KW - Mental Health Therapies KW - Drug Administration Schedule KW - Humans KW - Research -- standards KW - Professional Staff Committees KW - Mental Disorders -- drug therapy KW - Drug-Related Side Effects and Adverse Reactions KW - Psychiatry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69218458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=IRB+review+of+psychiatric+medication+discontinuation+and+symptom-provoking+studies.&rft.au=Rosenstein%2C+D+L&rft.aulast=Rosenstein&rft.aufirst=D&rft.date=1999-10-15&rft.volume=46&rft.issue=8&rft.spage=1039&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-29 N1 - Date created - 1999-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - beta -Propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection AN - 17397238; 4626421 AB - Prokaryotic proteases demonstrate a variety of substrate-selection strategies that prevent uncontrolled protein degradation. Proteasomes and ClpXP-like proteases form oligomeric structures that exclude large substrates from central solvated chambers containing their active sites. Monomeric prolyl oligopeptidases have been shown to contain beta -propeller structures that similarly reduce access to their catalytic residues. By contrast, Tsp-like enzymes contain PDZ domains that are thought to specifically target C-terminal polypeptides. We have investigated the sequence of Thermoplasma acidophilum tricorn protease using recently-developed database search methods. The tricorn protease is known to associate into a 20 hexamer capsid enclosing an extremely large cavity that is 37 nm in diameter. It is unknown, however, how this enzyme selects its small oligopeptide substrates. Our results demonstrate the presence in tricorn protease of a PDZ domain and two predicted six-bladed beta -propeller domains. We suggest that the PDZ domain is involved in targeting non-polar C-terminal peptides, similar to those generated by the T. acidophilum proteasome, whereas the beta -propeller domains serve to exclude large substrates from the tricorn protease active site in a similar manner to that previously indicated for prolyl oligopeptidase. JF - FEMS Microbiology Letters AU - Ponting, C P AU - Pallen, MJ AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health Bethesda, MD USA Y1 - 1999/10/15/ PY - 1999 DA - 1999 Oct 15 SP - 447 EP - 451 PB - Elsevier VL - 179 IS - 2 SN - 0378-1097, 0378-1097 KW - PDZ domain KW - substrate specificity KW - tricorn proteinase KW - Microbiology Abstracts B: Bacteriology KW - Thermoplasma acidophilum KW - Proteinase KW - Active sites KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17397238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=beta+-Propeller+repeats+and+a+PDZ+domain+in+the+tricorn+protease%3A+predicted+self-compartmentalisation+and+C-terminal+polypeptide-binding+strategies+of+substrate+selection&rft.au=Ponting%2C+C+P%3BPallen%2C+MJ&rft.aulast=Ponting&rft.aufirst=C&rft.date=1999-10-15&rft.volume=179&rft.issue=2&rft.spage=447&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/10.1016%2FS0378-1097%2899%2900418-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermoplasma acidophilum; Proteinase; Active sites DO - http://dx.doi.org/10.1016/S0378-1097(99)00418-8 ER - TY - JOUR T1 - Generation of a parainfluenza virus type 1 vaccine candidate by replacing the HN and F glycoproteins of the live-attenuated PIV3 cp45 vaccine virus with their PIV1 counterparts AN - 17405639; 4633014 AB - Parainfluenza virus type 1 (PIV1) is a major cause of croup in infants and young children, and a vaccine is needed to prevent the serious disease caused by this virus. In the present study, a live attenuated PIV1 vaccine candidate was generated by modification of the extensively-studied PIV3 cold-passaged (cp) cp45 vaccine candidate using the techniques of reverse genetics. The HN and F glycoproteins of the PIV3 cp45 candidate vaccine virus were replaced with those of PIV1. This created a live attenuated PIV1 vaccine candidate, termed rPIV3-1 cp45, which contained the attenuated background of the PIV3 cp45 vaccine virus together with the HN and F protective antigens of PIV1. Three of the 15 mutations of cp45 lie within the HN and F genes, and those in the F gene are attenuating. Thus, some attenuation might be lost by the HN and F glycoprotein replacement. To address this issue we also constructed a derivative of PIV3 cp45, designated rPIV3 cp45 (F sub(wt)HN sub(wt)), that possessed wild type PIV3 HN and F glycoproteins but retained the 12 other cp45 mutations. rPIV3 cp45 (F sub(wt)HN sub(wt)) replicated in the respiratory tract of hamsters to a level three- to four-fold higher than rPIV3 cp45, indicating that loss of the two attenuating mutations in the cp45 F gene effected a slight reduction in the overall attenuation of cp45 for hamsters. However, the chimeric rPIV3-1 cp45 virus was about 5-fold more restricted in replication in hamsters than rPIV3 cp45 and about 15- to 20-fold more restricted than rPIV3 cp45 (F sub(wt)HN sub(wt)). This suggests that two components contribute to the attenuation of the new chimeric rPIV3-1 cp45 PIV1 vaccine candidate: one being the 12 cp45 mutations, which provide most of the observed attenuation, and the other resulting from the introduction of the heterologous PIV1 HN and F proteins into PIV3 (i.e., a chimerization effect). rPIV3-1 cp45 was observed to be immunogenic and protective against challenge with wild type PIV1 in hamsters. This virus shows sufficient promise that it should be evaluated further as a candidate live attenuated vaccine strain for preventing severe lower respiratory tract PIV1 disease in infants and young children. JF - Vaccine AU - Skiadopoulos, M H AU - Tao, Tao AU - Surman AU - Collins, P L AU - Murphy, B R AD - NIH, Building 7; Rm 106; 7 Center Dr. MSC 0720, Bethesda, MD 20892-0720, USA, mskiadopoulos@atlas.niaid.nih.gov Y1 - 1999/10/14/ PY - 1999 DA - 1999 Oct 14 SP - 503 EP - 510 VL - 18 IS - 5-6 SN - 0264-410X, 0264-410X KW - man KW - immunology KW - glycoprotein F KW - glycoprotein HN KW - parainfluenza virus KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Immunology Abstracts KW - Vaccines KW - Human parainfluenza virus 1 KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17405639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Generation+of+a+parainfluenza+virus+type+1+vaccine+candidate+by+replacing+the+HN+and+F+glycoproteins+of+the+live-attenuated+PIV3+cp45+vaccine+virus+with+their+PIV1+counterparts&rft.au=Skiadopoulos%2C+M+H%3BTao%2C+Tao%3BSurman%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=1999-10-14&rft.volume=18&rft.issue=5-6&rft.spage=503&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human parainfluenza virus 1; Vaccines ER - TY - JOUR T1 - Science-based views of drug addiction and its treatment. AN - 70846908; 10527162 JF - JAMA AU - Leshner, A I AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. leshner@nih.gov Y1 - 1999/10/13/ PY - 1999 DA - 1999 Oct 13 SP - 1314 EP - 1316 VL - 282 IS - 14 SN - 0098-7484, 0098-7484 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Substance-Related Disorders -- therapy KW - Substance-Related Disorders -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70846908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Science-based+views+of+drug+addiction+and+its+treatment.&rft.au=Leshner%2C+A+I&rft.aulast=Leshner&rft.aufirst=A&rft.date=1999-10-13&rft.volume=282&rft.issue=14&rft.spage=1314&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-27 N1 - Date created - 1999-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BRCA1-associated growth arrest is RB-dependent. AN - 70826348; 10518542 AB - BRCA1 is a susceptibility gene for breast and ovarian cancer with growth-inhibitory activity for which the mechanism of action remains unclear. When introduced into cells, BRCA1 inhibits growth of some but not all cell lines. In an attempt to uncover the mechanism of growth suppression by BRCA1, we examined a panel of cell lines for their ability to reduce colony outgrowth in response to BRCA1 overexpression. Of all variables tested, only those cells with wild-type pRb were sensitive to BRCA1-induced growth suppression. In cells with an intact rb gene, inactivation of pRb by HPV E7 abrogates the growth arrest imposed by BRCA1. In accordance with these observations, we found that BRCA1 could not suppress BrdUrd uptake in primary fibroblasts from rb-/- mice and exhibited an intermediate ability to inhibit DNA synthesis in rb+/- as compared with rb+/+ cells. We further found that the BRCA1 protein complexes with the hypophosphorylated form of pRb. This binding is localized to amino acids 304-394 of BRCA1 protein and requires the ABC domain of pRb. In-frame deletion of BRCA1 fragment involved in interaction with pRb completely abolished the growth-suppressive property of BRCA1. Although it has been reported that BRCA1 interacts with p53, we find the p53 status did not affect the ability of BRCA1 to suppress colony formation. Our data suggest that the growth suppressor function of BRCA1 depends, at least in part, on Rb. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Aprelikova, O N AU - Fang, B S AU - Meissner, E G AU - Cotter, S AU - Campbell, M AU - Kuthiala, A AU - Bessho, M AU - Jensen, R A AU - Liu, E T AD - Section of Molecular Signaling and Oncogenesis, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/10/12/ PY - 1999 DA - 1999 Oct 12 SP - 11866 EP - 11871 VL - 96 IS - 21 SN - 0027-8424, 0027-8424 KW - BRCA1 Protein KW - 0 KW - Oncogene Proteins, Viral KW - Papillomavirus E7 Proteins KW - Retinoblastoma Protein KW - Tumor Suppressor Protein p53 KW - oncogene protein E7, Human papillomavirus type 16 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Animals KW - Plasmids -- metabolism KW - Adenoviridae -- metabolism KW - Humans KW - Glutathione Transferase -- metabolism KW - Precipitin Tests KW - Tumor Suppressor Protein p53 -- metabolism KW - Fibroblasts -- metabolism KW - Oncogene Proteins, Viral -- metabolism KW - Mutagenesis KW - Phenotype KW - Blotting, Western KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Models, Genetic KW - Cell Division -- genetics KW - Gene Expression Regulation, Developmental KW - Cell Cycle -- physiology KW - BRCA1 Protein -- physiology KW - BRCA1 Protein -- genetics KW - Retinoblastoma Protein -- metabolism KW - BRCA1 Protein -- metabolism KW - Retinoblastoma Protein -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70826348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=BRCA1-associated+growth+arrest+is+RB-dependent.&rft.au=Aprelikova%2C+O+N%3BFang%2C+B+S%3BMeissner%2C+E+G%3BCotter%2C+S%3BCampbell%2C+M%3BKuthiala%2C+A%3BBessho%2C+M%3BJensen%2C+R+A%3BLiu%2C+E+T&rft.aulast=Aprelikova&rft.aufirst=O&rft.date=1999-10-12&rft.volume=96&rft.issue=21&rft.spage=11866&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-24 N1 - Date created - 1999-11-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1985 Jul 11-17;316(6024):158-60 [3892307] Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):4983-8 [10220405] J Virol. 1992 Dec;66(12):6893-902 [1331501] J Biol Chem. 1992 Dec 25;267(36):25998-6003 [1334491] Am J Hum Genet. 1993 Apr;52(4):678-701 [8460634] J Virol. 1993 May;67(5):2521-8 [8386265] Nat Genet. 1995 Apr;9(4):444-50 [7795653] Cancer Res. 1995 Oct 15;55(20):4561-5 [7553629] Nat Genet. 1996 Mar;12(3):298-302 [8589721] Cell. 1996 Jun 28;85(7):1009-23 [8674108] Genes Dev. 1996 Jul 15;10(14):1835-43 [8698242] Nature. 1996 Aug 22;382(6593):678-9 [8751436] Cell Growth Differ. 1996 Jun;7(6):711-5 [8780884] Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13595-9 [8942979] Cell. 1997 Jan 24;88(2):265-75 [9008167] Nature. 1997 Sep 11;389(6647):187-90 [9296497] Mol Cell Biol. 1998 Jan;18(1):629-43 [9418909] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2302-6 [9482880] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14 [9482916] Oncogene. 1998 Apr 2;16(13):1713-21 [9582019] Cell. 1990 Aug 24;62(4):671-80 [2143698] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single amino acids determine specificity of binding of protein kinase A regulatory subunits by protein kinase A anchoring proteins. AN - 70802432; 10506157 AB - Cyclic AMP-dependent protein kinase is tethered to protein kinase A anchoring proteins (AKAPs) through regulatory subunits (R) by RIalpha-specific, RIIalpha-specific, or RIalpha/RIIalpha dual-specific binding. Ala- and Val-scanning mutagenesis determined that hydrophobic amino acids at three homologous positions are required for binding of RIalpha to FSC1/AKAP82 domain B and RIIalpha to AKAP Ht31. A mutation at the middle position reversed the binding specificity of both AKAPs, and mutations at this same position of the dual-specific domain A of FSC1/AKAP82 converted it into either an RIalpha or RIIalpha binding domain. This suggests that hydrophobic amino acids at three conserved positions within the primary sequence and an amphipathic helix of AKAPs are required for cyclic AMP-dependent protein kinase binding, with the size of the aliphatic side chain at the middle position determining RIalpha or RIIalpha binding specificity. JF - The Journal of biological chemistry AU - Miki, K AU - Eddy, E M AD - Gamete Biology Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/10/08/ PY - 1999 DA - 1999 Oct 08 SP - 29057 EP - 29062 VL - 274 IS - 41 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - Carrier Proteins KW - Isoenzymes KW - Proteins KW - Seminal Plasma Proteins KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Carrier Proteins -- chemistry KW - Amino Acids -- chemistry KW - Carrier Proteins -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Consensus Sequence KW - Protein Binding KW - Isoenzymes -- metabolism KW - Mutagenesis KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Proteins -- chemistry KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70802432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Single+amino+acids+determine+specificity+of+binding+of+protein+kinase+A+regulatory+subunits+by+protein+kinase+A+anchoring+proteins.&rft.au=Miki%2C+K%3BEddy%2C+E+M&rft.aulast=Miki&rft.aufirst=K&rft.date=1999-10-08&rft.volume=274&rft.issue=41&rft.spage=29057&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-09 N1 - Date created - 1999-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Localization of the linker domain of Ca2+/calmodulin-dependent protein kinase II. AN - 70837231; 10512734 AB - Electron micrographs of rotary shadowed replicas of alpha-Ca2+/calmodulin-dependent protein kinase II reveal a flower-shaped multimeric molecule with a central particle surrounded by 8-10 smaller peripheral particles. Peripheral particles are attached to the central particle by thin arms or "linkers." Movement of peripheral particles to contact each other for autophosphorylation is likely to involve these linkers. It has generally been accepted that the segment 317-328 of the alpha-subunit constitutes the linker domain. In the present study we test this assumption by generating a mutant lacking the proposed sequence. The mutant has biochemical and morphological properties similar to those of the wild type, and a thin linker is occasionally observed in replicas from either type. The results indicate that the deleted sequence does not correspond to the linker domain. This conclusion, combined with observations from two recent studies which identify the C-terminal domain involved in oligomerization, narrows down the location of the linker domain within the sequence 330-354. Copyright 1999 Academic Press. JF - Biochemical and biophysical research communications AU - Dosemeci, A AU - Reese, T S AU - Petersen, J D AU - Choi, C AU - Beushausen, S AD - Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. ayse@codon.nih.gov Y1 - 1999/10/05/ PY - 1999 DA - 1999 Oct 05 SP - 657 EP - 662 VL - 263 IS - 3 SN - 0006-291X, 0006-291X KW - Macromolecular Substances KW - 0 KW - Peptide Fragments KW - Recombinant Proteins KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Index Medicus KW - Animals KW - Spodoptera KW - Amino Acid Sequence KW - Mice KW - Peptide Fragments -- ultrastructure KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Peptide Fragments -- chemistry KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Recombinant Proteins -- ultrastructure KW - Molecular Sequence Data KW - Microscopy, Electron KW - Recombinant Proteins -- chemistry KW - Cell Line KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- ultrastructure KW - Calcium-Calmodulin-Dependent Protein Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70837231?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Localization+of+the+linker+domain+of+Ca2%2B%2Fcalmodulin-dependent+protein+kinase+II.&rft.au=Dosemeci%2C+A%3BReese%2C+T+S%3BPetersen%2C+J+D%3BChoi%2C+C%3BBeushausen%2C+S&rft.aulast=Dosemeci&rft.aufirst=A&rft.date=1999-10-05&rft.volume=263&rft.issue=3&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-23 N1 - Date created - 1999-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. AN - 70834248; 10512739 AB - Subsaturating levels of tetrahydrobiopterin (BH(4)), an essential cofactor for nitric oxide synthase (NOS), can lead to endothelial dysfunction as a result of decreased production of nitric oxide. Furthermore, insufficient BH(4) can also result in NOS-uncoupled production of reactive oxygen intermediates, such as superoxide anion and hydrogen peroxide. Nitric oxide and superoxide react rapidly to form peroxynitrite, which may be the reactive species responsible for many of the toxic effects of nitric oxide. Here we show that BH(4) is a primary target for peroxynitrite-catalyzed oxidation because at pH 7.4, physiologically relevant concentrations of BH(4) are oxidized rapidly by low concentrations of peroxynitrite. Peroxynitrite oxidizes BH(4) to quinonoid 5,6-dihydrobiopterin and a large proportion of the quinonoid isomer readily loses its side chain to form 7,8-dihydropterin which is not a cofactor for nitric oxide synthase. Thus, abnormally low levels of BH(4) can promote a cycle of its own destruction mediated by nitric oxide synthase-dependent formation of peroxynitrite. This mechanism might contribute to vascular endothelial dysfunction induced by oxidative stress. Copyright 1999 Academic Press. JF - Biochemical and biophysical research communications AU - Milstien, S AU - Katusic, Z AD - Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892, USA. milstien@codon.nih.gov Y1 - 1999/10/05/ PY - 1999 DA - 1999 Oct 05 SP - 681 EP - 684 VL - 263 IS - 3 SN - 0006-291X, 0006-291X KW - Antioxidants KW - 0 KW - Nitrates KW - Oxidants KW - Pteridines KW - Biopterin KW - 22150-76-1 KW - peroxynitric acid KW - 26404-66-0 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - sapropterin KW - EGX657432I KW - Index Medicus KW - Pteridines -- chemistry KW - Oxidation-Reduction KW - Kinetics KW - Nitric Oxide Synthase -- metabolism KW - Biopterin -- analogs & derivatives KW - Oxidants -- chemistry KW - Biopterin -- chemistry KW - Antioxidants -- chemistry KW - Nitrates -- chemistry KW - Endothelium, Vascular -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70834248?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Oxidation+of+tetrahydrobiopterin+by+peroxynitrite%3A+implications+for+vascular+endothelial+function.&rft.au=Milstien%2C+S%3BKatusic%2C+Z&rft.aulast=Milstien&rft.aufirst=S&rft.date=1999-10-05&rft.volume=263&rft.issue=3&rft.spage=681&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-23 N1 - Date created - 1999-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immortalization of chinchilla middle ear epithelial cells by adenovirus 12-simian virus 40 hybrid virus. AN - 85409982; pmid-10526847 AB - In order to study the cellular and molecular mechanisms of the pathogenesis of otitis media, a chinchilla middle ear epithelial cell line (CMEE-1) with differentiated cell characteristics was established by infection of a primary culture with the adenovirus 12-simian virus 40 (Ad12-SV40) hybrid. This cell line has been in continuous culture for 42 passages, whereas the parent cells underwent senescence and died at the 8th passage. The cell line also retains epithelial morphology and expresses cytokeratin polypeptides 4, 7, and 18, characteristic markers for epithelia. In Western blots of cell proteins, bands at 94 and 53 kd were labeled after binding antibodies against SV40 large T antigen and p53, respectively. Karyotype analysis showed that the cell line is derived from chinchilla epithelial cells. These findings confirm that the cell line is a chinchilla epithelial cell immortalized by the hybrid virus. JF - The Annals of otology, rhinology, and laryngology AU - Jin, S AU - Gu, X X AU - Rhim, J S AU - Lim, D J AD - Laboratory of Cellular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, USA. Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 934 EP - 943 VL - 108 IS - 10 SN - 0003-4894, 0003-4894 KW - National Library of Medicine KW - Epithelial Cells -- virology KW - Karyotyping KW - Chinchilla KW - Animals KW - Hybridization, Genetic KW - Cell Culture Techniques KW - Cell Line, Transformed KW - Time Factors KW - Male KW - Simian virus 40 -- genetics KW - Ear, Middle -- cytology KW - Cell Transformation, Viral KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85409982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Immortalization+of+chinchilla+middle+ear+epithelial+cells+by+adenovirus+12-simian+virus+40+hybrid+virus.&rft.au=Jin%2C+S%3BGu%2C+X+X%3BRhim%2C+J+S%3BLim%2C+D+J&rft.aulast=Jin&rft.aufirst=S&rft.date=1999-10-01&rft.volume=108&rft.issue=10&rft.spage=934&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - Solution of the inverse problem for a linear cochlear model: a tonotopic cochlear amplifier. AN - 85409482; pmid-10530013 AB - The extraordinary fine-tuning characteristic of normal mammalian hearing is attributed to physiological mechanisms collectively known as the cochlear amplifier (CA), which amplifies and sharpens the basilar membrane (BM) vibration response to incoming acoustic pressure oscillations. Electromechanical properties of outer hair cells (OHCs) are believed to be the critical component of the CA, but its "circuitry" as yet remains unknown. Here, the required frequency-space response characteristics of the CA are computationally determined when typical in vivo tuning data are introduced as input to a linear hydroelastic cochlear model whose cross-sectional dynamics are represented by two coupled vibrational degrees of freedom. It is assumed that the CA senses motion at the tectorial membrane (TM) reticular lamina (RL) and applies proportional, equal, and opposite forces to the BM and the RL. The results show the CA to be tonotopically tuned, meaning it conforms to a space-frequency similarity principle like other cochlear dynamical responses. This requires that the active mechanism use information distributed along the cochlear partition. The physiological mechanism responsible for such behavior remains unknown, but here the computed CA characteristics can be qualitatively reproduced by a circuit spanning the length of the cochlea. This does not preclude other mechanisms, but is intended to motivate closer experimental investigation of extracellular and intercellular ionic flow pathways. JF - The Journal of the Acoustical Society of America AU - Dimitriadis, E K AU - Chadwick, R S AD - Bioengineering and Physical Sciences Program/ORS/OD, National Institutes of Health, Bethesda, Maryland 20892, USA. dimitria@helix.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 1880 EP - 1892 VL - 106 IS - 4 Pt 1 SN - 0001-4966, 0001-4966 KW - Index Medicus KW - National Library of Medicine KW - Hair Cells, Auditory, Outer -- physiology KW - Animals KW - Basilar Membrane -- physiology KW - Biomechanics KW - Linear Models KW - Cochlea -- physiology KW - Models, Biological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85409482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Acoustical+Society+of+America&rft.atitle=Solution+of+the+inverse+problem+for+a+linear+cochlear+model%3A+a+tonotopic+cochlear+amplifier.&rft.au=Dimitriadis%2C+E+K%3BChadwick%2C+R+S&rft.aulast=Dimitriadis&rft.aufirst=E&rft.date=1999-10-01&rft.volume=106&rft.issue=4+Pt+1&rft.spage=1880&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Acoustical+Society+of+America&rft.issn=00014966&rft_id=info:doi/ LA - English (eng) DB - ComDisDome N1 - Date revised - 2010-04-12 N1 - Last updated - 2010-09-25 ER - TY - JOUR T1 - The use of state-dependent modulation of spinal reflexes as a tool to investigate the organization of spinal interneurons. AN - 85236121; pmid-10501799 AB - This review examines the proposition that state-dependent modulation of transmission through spinal reflex pathways can be used as an investigative tool to reveal details about the organization of spinal interneurons into functional circuits. The first set of examples includes the use of spinal and supraspinal lesions, as well as the administration of the drug l-dihydroxyphenylalanine (l-DOPA), to produce different, relatively stable "states" of the central nervous system (CNS), revealing previously unsuspected spinal pathways activated by the flexor reflex afferents (FRA). The second set of examples deals with the use of fictive locomotion and scratching to investigate the organization of oligosynaptic excitatory and inhibitory reflex pathways from cutaneous and muscle afferents. As in the first set of examples, several hitherto unknown reflex pathways have been found only during the flexion or extension phases of rhythmic locomotion, which are regarded as different CNS states. Differences in the patterns of control can be used to infer the existence of distinct sets of reflex pathway interneurons that have remarkably precise input/output relations. JF - Experimental Brain Research AU - Burke, R E AD - Laboratory of Neural Control, Bldg. 49, Rm. 3A50, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4455, USA, PY - 1999 SP - 263 EP - 277 VL - 128 IS - 3 SN - 0014-4819, 0014-4819 KW - Interneurons KW - Levodopa KW - Spinal Cord KW - Locomotion KW - Excitatory Postsynaptic Potentials KW - Human KW - Neural Pathways KW - Animal KW - Dopamine Agents KW - Reflex KW - Decerebrate State KW - Afferent Pathways KW - Motor Neurons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85236121?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+Brain+Research&rft.atitle=The+use+of+state-dependent+modulation+of+spinal+reflexes+as+a+tool+to+investigate+the+organization+of+spinal+interneurons.&rft.au=Burke%2C+R+E&rft.aulast=Burke&rft.aufirst=R&rft.date=1999-10-01&rft.volume=128&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Experimental+Brain+Research&rft.issn=00144819&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - In vivo production of nitric oxide after administration of cyclohexanone oxime. AN - 70863396; 10525271 AB - Cyclohexanone oxime (CHOX), an intermediate used in the synthesis of polycaprolactam (Nylon-6), has been reported to be hematotoxic in Fischer rats. The in vivo metabolism of CHOX was found to release nitric oxide, which was detected in venous blood by electron paramagnetic resonance spectroscopy as the nitrosylhemoglobin complex. In vitro incubation of CHOX with venous blood resulted in the formation of the characteristic nitrosylhemoglobin complex, suggesting that the blood was a possible site for metabolism. Excessive nitric oxide production may, in part, contribute to the observed toxicity of CHOX. JF - Chemical research in toxicology AU - Glover, R E AU - Corbett, J T AU - Burka, L T AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, National Institutes of Health, P.O. Box 12233, Research Triangle Park, North Carolina 27709, USA. glover1@niehs.nih.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 952 EP - 957 VL - 12 IS - 10 SN - 0893-228X, 0893-228X KW - Cyclohexanones KW - 0 KW - Cytochromes KW - Hemoglobins KW - cyclohexanone oxime KW - 2U60L00CGF KW - Nitric Oxide KW - 31C4KY9ESH KW - deoxyhemoglobin KW - 9008-02-0 KW - Methemoglobin KW - 9008-37-1 KW - cytochrome P420 KW - 9035-49-8 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Hemoglobins -- metabolism KW - Electron Spin Resonance Spectroscopy KW - Methemoglobin -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Erythrocytes -- metabolism KW - Male KW - Chromatography, High Pressure Liquid KW - Cytochromes -- metabolism KW - Nitric Oxide -- blood KW - Cyclohexanones -- pharmacology KW - Nitric Oxide -- metabolism KW - Nitric Oxide -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70863396?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=In+vivo+production+of+nitric+oxide+after+administration+of+cyclohexanone+oxime.&rft.au=Glover%2C+R+E%3BCorbett%2C+J+T%3BBurka%2C+L+T%3BMason%2C+R+P&rft.aulast=Glover&rft.aufirst=R&rft.date=1999-10-01&rft.volume=12&rft.issue=10&rft.spage=952&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Naltrexone shortened opioid detoxification with buprenorphine. AN - 70845059; 10529020 AB - This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance. JF - Drug and alcohol dependence AU - Umbricht, A AU - Montoya, I D AU - Hoover, D R AU - Demuth, K L AU - Chiang, C T AU - Preston, K L AD - NIDA Intramural Research Program, Addiction Research Center, Baltimore, MD, USA. aumbri@intra.nida.nih.gov Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 181 EP - 190 VL - 56 IS - 3 SN - 0376-8716, 0376-8716 KW - Analgesics KW - 0 KW - Narcotic Antagonists KW - Buprenorphine KW - 40D3SCR4GZ KW - Naltrexone KW - 5S6W795CQM KW - Heroin KW - 70D95007SX KW - Clonidine KW - MN3L5RMN02 KW - Index Medicus KW - Drug Therapy, Combination KW - Drug Interactions KW - Double-Blind Method KW - Area Under Curve KW - Humans KW - Adult KW - Clonidine -- therapeutic use KW - Analgesics -- therapeutic use KW - Male KW - Female KW - Substance Withdrawal Syndrome -- physiopathology KW - Heroin -- adverse effects KW - Buprenorphine -- therapeutic use KW - Narcotic Antagonists -- therapeutic use KW - Substance Withdrawal Syndrome -- drug therapy KW - Heroin Dependence -- rehabilitation KW - Naltrexone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70845059?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Drug+and+alcohol+dependence&rft.atitle=Naltrexone+shortened+opioid+detoxification+with+buprenorphine.&rft.au=Umbricht%2C+A%3BMontoya%2C+I+D%3BHoover%2C+D+R%3BDemuth%2C+K+L%3BChiang%2C+C+T%3BPreston%2C+K+L&rft.aulast=Umbricht&rft.aufirst=A&rft.date=1999-10-01&rft.volume=56&rft.issue=3&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Drug+and+alcohol+dependence&rft.issn=03768716&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-16 N1 - Date created - 1999-11-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia. AN - 70841309; 10518181 AB - This study sought to determine whether thought disorder induced in healthy volunteers by the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine resembles the thought disorder found in patients with schizophrenia. The Scale for the Assessment of Thought, Language, and Communication was used to assess thought disorder in healthy volunteers (N = 10) who received subanesthetic doses of ketamine and in a group of clinically stable inpatients with schizophrenia (N = 15) who did not receive ketamine. Mean scores on the Scale for the Assessment of Thought, Language, and Communication for patients with schizophrenia and healthy volunteers receiving ketamine did not differ significantly. Moreover, three of the four highest rated test items in both groups were the same. These data suggest that ketamine-induced thought disorder in healthy volunteers is not dissimilar to the thought disorder in patients with schizophrenia and provide support for the involvement of the NMDA receptor in a cardinal symptom of schizophrenia. JF - The American journal of psychiatry AU - Adler, C M AU - Malhotra, A K AU - Elman, I AU - Goldberg, T AU - Egan, M AU - Pickar, D AU - Breier, A AD - Experimental Therapeutics Branch, NIMH, Bethesda, Md., USA. cal.adler@psychiatry.uc.edu Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 1646 EP - 1649 VL - 156 IS - 10 SN - 0002-953X, 0002-953X KW - Receptors, N-Methyl-D-Aspartate KW - 0 KW - Ketamine KW - 690G0D6V8H KW - Abridged Index Medicus KW - Index Medicus KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Diagnosis, Differential KW - Humans KW - Adult KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Male KW - Female KW - Cognition Disorders -- diagnosis KW - Schizophrenia -- diagnosis KW - Schizophrenic Psychology KW - Cognition Disorders -- chemically induced KW - Schizophrenia -- physiopathology KW - Cognition Disorders -- physiopathology KW - Ketamine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70841309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Comparison+of+ketamine-induced+thought+disorder+in+healthy+volunteers+and+thought+disorder+in+schizophrenia.&rft.au=Adler%2C+C+M%3BMalhotra%2C+A+K%3BElman%2C+I%3BGoldberg%2C+T%3BEgan%2C+M%3BPickar%2C+D%3BBreier%2C+A&rft.aulast=Adler&rft.aufirst=C&rft.date=1999-10-01&rft.volume=156&rft.issue=10&rft.spage=1646&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Loss of responsiveness to transforming growth factor beta induces malignant transformation of nontumorigenic rat prostate epithelial cells. AN - 70830868; 10519393 AB - Transforming growth factor (TGF)-betas are multifunctional growth factors, the properties of which include the potent inhibition of epithelial cell growth. Expression patterns of TGF-betas and TGF-beta receptors in the normal prostate indicate that these growth regulators play key roles in prostatic development and proliferative homeostasis. Importantly, TGF-beta receptor levels are frequently diminished in malignant human prostate tissue. To test the hypothesis that loss of TGF-beta responsiveness is causally involved in the tumorigenic process, we have used retroviral transduction to introduce a dominant-negative mutant type II TGF-beta receptor (DNR) into the premalignant rat prostatic epithelial cell line, NRP-152. High-level expression of the DNR abolished the ability of TGF-beta to inhibit cell growth, to promote cell differentiation, and to induce apoptosis, and it partially blocked the induction of extracellular matrix gene expression. When injected into nude mice, NRP-152-DNR cells formed carcinomas at 13 of 34 sites, compared with 0 of 30 sites for parental and control cells (P = 0.0001). We conclude that the type II TGF-beta receptor is an important tumor suppressor in the prostate, and furthermore, that loss of TGF-beta responsiveness can contribute early in the tumorigenic process by causing the malignant transformation of preneoplastic cells. JF - Cancer research AU - Tang, B AU - de Castro, K AU - Barnes, H E AU - Parks, W T AU - Stewart, L AU - Böttinger, E P AU - Danielpour, D AU - Wakefield, L M AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 4834 EP - 4842 VL - 59 IS - 19 SN - 0008-5472, 0008-5472 KW - Extracellular Matrix Proteins KW - 0 KW - Receptors, Transforming Growth Factor beta KW - Recombinant Proteins KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Animals KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Mice, Nude KW - Rats KW - Epithelial Cells KW - Transfection KW - Recombinant Proteins -- metabolism KW - Apoptosis -- drug effects KW - Transplantation, Heterologous KW - Cell Differentiation -- drug effects KW - Prostate KW - Cell Line KW - Male KW - Transforming Growth Factor beta -- pharmacology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Prostatic Neoplasms -- pathology KW - Receptors, Transforming Growth Factor beta -- physiology KW - Extracellular Matrix Proteins -- genetics KW - Prostatic Neoplasms -- genetics KW - Gene Expression Regulation -- drug effects KW - Cell Transformation, Neoplastic UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70830868?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Loss+of+responsiveness+to+transforming+growth+factor+beta+induces+malignant+transformation+of+nontumorigenic+rat+prostate+epithelial+cells.&rft.au=Tang%2C+B%3Bde+Castro%2C+K%3BBarnes%2C+H+E%3BParks%2C+W+T%3BStewart%2C+L%3BB%C3%B6ttinger%2C+E+P%3BDanielpour%2C+D%3BWakefield%2C+L+M&rft.aulast=Tang&rft.aufirst=B&rft.date=1999-10-01&rft.volume=59&rft.issue=19&rft.spage=4834&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. AN - 70829846; 10519378 AB - One major challenge facing today's cancer researchers and toxicologists is the development of new approaches for the identification of carcinogens and other environmental hazards. Here, we describe the potential impact of emerging technologies for measuring gene expression profiles on carcinogen identification and on the general field of toxicology. An example of one of these technologies is the use of cDNA microarray chips. We provide an overview to the key questions that are confronting investigators charged with determining the relative safety of natural or synthetic chemicals to which humans are exposed, followed by a discussion of how cDNA microarray technology may be applied to these questions. Gene chip technology is still a relatively new technology, and only a handful of studies have demonstrated its utility. However, as the technical hurdles to development are passed, the use of this methodology in addressing the questions raised here will be critical to increase the sensitivity of detection of the potential toxic effects of environmental chemicals and to understand their risks to humans. JF - Cancer research AU - Afshari, C A AU - Nuwaysir, E F AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 4759 EP - 4760 VL - 59 IS - 19 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA, Complementary KW - Index Medicus KW - Oligonucleotide Array Sequence Analysis KW - Humans KW - Pharmacology, Clinical -- methods KW - Toxicology -- methods KW - Gene Library KW - Consumer Product Safety KW - Carcinogens -- classification KW - Carcinogens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70829846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Application+of+complementary+DNA+microarray+technology+to+carcinogen+identification%2C+toxicology%2C+and+drug+safety+evaluation.&rft.au=Afshari%2C+C+A%3BNuwaysir%2C+E+F%3BBarrett%2C+J+C&rft.aulast=Afshari&rft.aufirst=C&rft.date=1999-10-01&rft.volume=59&rft.issue=19&rft.spage=4759&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiotherapy and concurrent continuous infusion of cisplatin with adjuvant surgery in nonresectable Stage III lung carcinoma: short- and long-term results of a Phase II study. AN - 70827846; 10524413 AB - Cisplatin-enhanced radiotherapy plus adjuvant surgery was evaluated in nonresectable non-small cell lung carcinoma (NSCLC). Doses of 50 Gy (administered in standard fractionation in 5 weeks) were delivered with concurrent cisplatin in continuous infusion (daily dose: 4 mg/m2), to 32 Stage IIIa and 45 Stage IIIb patients enrolled in a Phase II study. Patients without progression underwent surgery. Esophagitis (64%), nausea/vomiting (34%), and pulmonary toxicity (14%) were the main side effects. Grade 3 toxicity occurred in 4 instances. A clinical locoregional major response was achieved by 55 patients (there were 10 complete responses). Forty patients underwent surgery, 7 with a nonradical procedure. Seven patients died due to surgery-related complications, which were significantly impacted by right pneumonectomy (71% vs. 6% of the other procedures, p < 0.0001). Eighteen of the 40 surgical patients were assessed to be without viable tumor and 11 with microresidual carcinoma. There were 13 disease-free, 5-year survivors. Toxicity was low but activity high with the chemoradiotherapy. Adjuvant surgery increased the rate of complete responses, but right pneumonectomy had an unacceptable mortality. The role of surgery needs further refinement. Integration of the chemoradiotherapy schedule with cisplatin-based induction chemotherapy is advisable. JF - International journal of radiation oncology, biology, physics AU - Bedini, A V AU - Tavecchio, L AU - Gramaglia, A AU - Villa, S AU - Palazzi, M AD - Division of Thoracic Surgery, National Cancer Institute, Milan, Italy. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 613 EP - 621 VL - 45 IS - 3 SN - 0360-3016, 0360-3016 KW - Radiation-Sensitizing Agents KW - 0 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Neoplasm Staging KW - Combined Modality Therapy KW - Radiotherapy Dosage KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Radiotherapy -- adverse effects KW - Cisplatin -- therapeutic use KW - Lung Neoplasms -- radiotherapy KW - Carcinoma, Non-Small-Cell Lung -- surgery KW - Radiation-Sensitizing Agents -- therapeutic use KW - Lung Neoplasms -- surgery KW - Lung Neoplasms -- pathology KW - Carcinoma, Non-Small-Cell Lung -- radiotherapy KW - Carcinoma, Non-Small-Cell Lung -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70827846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.atitle=Radiotherapy+and+concurrent+continuous+infusion+of+cisplatin+with+adjuvant+surgery+in+nonresectable+Stage+III+lung+carcinoma%3A+short-+and+long-term+results+of+a+Phase+II+study.&rft.au=Bedini%2C+A+V%3BTavecchio%2C+L%3BGramaglia%2C+A%3BVilla%2C+S%3BPalazzi%2C+M&rft.aulast=Bedini&rft.aufirst=A&rft.date=1999-10-01&rft.volume=45&rft.issue=3&rft.spage=613&rft.isbn=&rft.btitle=&rft.title=International+journal+of+radiation+oncology%2C+biology%2C+physics&rft.issn=03603016&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-27 N1 - Date created - 1999-10-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relative effectiveness of the implantable cardioverter-defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus Implantable Defibrillators. AN - 70823596; 10520795 AB - We sought to assess the effect of baseline ejection fraction on survival difference between patients with life-threatening ventricular arrhythmias who were treated with an antiarrhythmic drug (AAD) or implantable cardioverter-defibrillator (ICD). The Antiarrhythmics Versus Implantable Defibrillators (AVID) study demonstrated improved survival in patients with ventricular fibrillation or ventricular tachycardia with a left ventricular ejection fraction (LVEF) < or =0.40 or hemodynamic compromise. Survival differences between AAD-treated and ICD-treated patients entered into the AVID study (patients presenting with sustained ventricular arrhythmia associated with an LVEF < or =0.40 or hemodynamic compromise) were compared at different levels of ejection fraction. In patients with an LVEF > or =0.35, there was no difference in survival between AAD-treated and ICD-treated patients. A test for interaction was not significant, but had low power to detect an interaction. For patients with an LVEF 0.20 to 0.34, there was a significantly improved survival with ICD as compared with AAD therapy. In the smaller subgroup with an LVEF <0.20, the same magnitude of survival difference was seen as that in the 0.20 to 0.34 LVEF subgroup, but the difference did not reach statistical significance. These data suggest that patients with relatively well-preserved LVEF (> or =0.35) may not have better survival when treated with the ICD as compared with AADs. At a lower LVEF, the ICD appears to offer improved survival as compared with AADs. Prospective studies with larger patient numbers are needed to assess the effect of relatively well-preserved ejection fraction (> or =0.35) on the relative treatment effect of AADs and the ICDs. JF - Journal of the American College of Cardiology AU - Domanski, M J AU - Sakseena, S AU - Epstein, A E AU - Hallstrom, A P AU - Brodsky, M A AU - Kim, S AU - Lancaster, S AU - Schron, E AD - Clinical Trials Group, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 1090 EP - 1095 VL - 34 IS - 4 SN - 0735-1097, 0735-1097 KW - Anti-Arrhythmia Agents KW - 0 KW - Amiodarone KW - N3RQ532IUT KW - Abridged Index Medicus KW - Index Medicus KW - Ventricular Function, Left -- drug effects KW - Hemodynamics -- drug effects KW - Hemodynamics -- physiology KW - Humans KW - Prognosis KW - Ventricular Function, Left -- physiology KW - Aged KW - Stroke Volume -- physiology KW - Survival Rate KW - Treatment Outcome KW - Middle Aged KW - Stroke Volume -- drug effects KW - Female KW - Male KW - Tachycardia, Ventricular -- mortality KW - Ventricular Fibrillation -- therapy KW - Tachycardia, Ventricular -- therapy KW - Amiodarone -- adverse effects KW - Ventricular Dysfunction, Left -- physiopathology KW - Ventricular Fibrillation -- mortality KW - Anti-Arrhythmia Agents -- adverse effects KW - Tachycardia, Ventricular -- physiopathology KW - Ventricular Fibrillation -- physiopathology KW - Anti-Arrhythmia Agents -- administration & dosage KW - Ventricular Dysfunction, Left -- mortality KW - Defibrillators, Implantable KW - Amiodarone -- administration & dosage KW - Ventricular Dysfunction, Left -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70823596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+College+of+Cardiology&rft.atitle=Relative+effectiveness+of+the+implantable+cardioverter-defibrillator+and+antiarrhythmic+drugs+in+patients+with+varying+degrees+of+left+ventricular+dysfunction+who+have+survived+malignant+ventricular+arrhythmias.+AVID+Investigators.+Antiarrhythmics+Versus+Implantable+Defibrillators.&rft.au=Domanski%2C+M+J%3BSakseena%2C+S%3BEpstein%2C+A+E%3BHallstrom%2C+A+P%3BBrodsky%2C+M+A%3BKim%2C+S%3BLancaster%2C+S%3BSchron%2C+E&rft.aulast=Domanski&rft.aufirst=M&rft.date=1999-10-01&rft.volume=34&rft.issue=4&rft.spage=1090&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+College+of+Cardiology&rft.issn=07351097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-27 N1 - Date created - 1999-10-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Coll Cardiol. 1999 Oct;34(4):1096-8 [10520796] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bispecific antibodies in cancer therapy. AN - 70802525; 10508714 AB - Based upon in vitro and animal studies, a number of Phase I and II clinical trials have been initiated to test whether bispecific antibodies could redirect immune effectors against tumor cells in cancer patients. Recently, results from those trials showed beneficial effects in some patients but it is clear many problems remain to be solved. In addition, molecular engineering approaches are providing new and improved sources of clinically relevant bispecific antibodies. JF - Current opinion in immunology AU - Segal, D M AU - Weiner, G J AU - Weiner, L M AD - Immune Targeting Section, Experimental Immunology Branch, National Cancer Institute, Building 10 Room 4B36, National Institutes of Health, Bethesda, MD 20892-1360, USA. dave_segal@nih.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 558 EP - 562 VL - 11 IS - 5 SN - 0952-7915, 0952-7915 KW - Antibodies, Bispecific KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Humans KW - Clinical Trials as Topic KW - Drug Design KW - Recombinant Proteins -- therapeutic use KW - Antibodies, Bispecific -- therapeutic use KW - Antibodies, Bispecific -- toxicity KW - Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70802525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+immunology&rft.atitle=Bispecific+antibodies+in+cancer+therapy.&rft.au=Segal%2C+D+M%3BWeiner%2C+G+J%3BWeiner%2C+L+M&rft.aulast=Segal&rft.aufirst=D&rft.date=1999-10-01&rft.volume=11&rft.issue=5&rft.spage=558&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+immunology&rft.issn=09527915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-15 N1 - Date created - 1999-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Linking environmental agents and autoimmune diseases. AN - 70801572; 10502527 JF - Environmental health perspectives AU - Cooper, G S AU - Germolec, D AU - Heindel, J AU - Selgrade, M Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 659 EP - 660 VL - 107 Suppl 5 KW - Environmental Pollutants KW - 0 KW - Index Medicus KW - Animals KW - Environmental Health KW - Epidemiologic Studies KW - Risk Factors KW - Humans KW - Environmental Exposure KW - Research Design KW - Autoimmune Diseases -- etiology KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70801572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Environmental+health+perspectives&rft.atitle=Linking+environmental+agents+and+autoimmune+diseases.&rft.au=Cooper%2C+G+S%3BGermolec%2C+D%3BHeindel%2C+J%3BSelgrade%2C+M&rft.aulast=Cooper&rft.aufirst=G&rft.date=1999-10-01&rft.volume=107+Suppl+5&rft.issue=&rft.spage=659&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-28 N1 - Date created - 2000-08-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Fundam Appl Toxicol. 1996 Sep;33(1):1-10 [8812200] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic instability in Gadd45a-deficient mice. AN - 70798639; 10508513 AB - Gadd45a-null mice generated by gene targeting exhibited several of the phenotypes characteristic of p53-deficient mice, including genomic instability, increased radiation carcinogenesis and a low frequency of exencephaly. Genomic instability was exemplified by aneuploidy, chromosome aberrations, gene amplification and centrosome amplification, and was accompanied by abnormalities in mitosis, cytokinesis and growth control. Unequal segregation of chromosomes due to multiple spindle poles during mitosis occurred in several Gadd45a -/- cell lineages and may contribute to the aneuploidy. Our results indicate that Gadd45a is one component of the p53 pathway that contributes to the maintenance of genomic stability. JF - Nature genetics AU - Hollander, M C AU - Sheikh, M S AU - Bulavin, D V AU - Lundgren, K AU - Augeri-Henmueller, L AU - Shehee, R AU - Molinaro, T A AU - Kim, K E AU - Tolosa, E AU - Ashwell, J D AU - Rosenberg, M P AU - Zhan, Q AU - Fernández-Salguero, P M AU - Morgan, W F AU - Deng, C X AU - Fornace, A J AD - Gene Response Section, DBS, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 176 EP - 184 VL - 23 IS - 2 SN - 1061-4036, 1061-4036 KW - GADD45 protein KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Animals KW - Gamma Rays -- adverse effects KW - Cell Cycle -- physiology KW - Fibroblasts -- cytology KW - Neoplasms -- genetics KW - Fibroblasts -- physiology KW - Mice, Knockout KW - Phenotype KW - Apoptosis -- genetics KW - G1 Phase KW - Cell Cycle -- genetics KW - Centrosome -- metabolism KW - Cell Transformation, Neoplastic -- genetics KW - Male KW - Thymus Hyperplasia -- genetics KW - Mice KW - Gene Deletion KW - Genes, ras -- genetics KW - Cell Aging KW - Thymus Hyperplasia -- pathology KW - Embryo, Mammalian -- cytology KW - Mice, Inbred C57BL KW - Female KW - Cell Division -- genetics KW - Neoplasms -- etiology KW - Proteins -- genetics KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70798639?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Genomic+instability+in+Gadd45a-deficient+mice.&rft.au=Hollander%2C+M+C%3BSheikh%2C+M+S%3BBulavin%2C+D+V%3BLundgren%2C+K%3BAugeri-Henmueller%2C+L%3BShehee%2C+R%3BMolinaro%2C+T+A%3BKim%2C+K+E%3BTolosa%2C+E%3BAshwell%2C+J+D%3BRosenberg%2C+M+P%3BZhan%2C+Q%3BFern%C3%A1ndez-Salguero%2C+P+M%3BMorgan%2C+W+F%3BDeng%2C+C+X%3BFornace%2C+A+J&rft.aulast=Hollander&rft.aufirst=M&rft.date=1999-10-01&rft.volume=23&rft.issue=2&rft.spage=176&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunotoxins in cancer therapy. AN - 70797037; 10508704 AB - Immunotoxins are composed of a protein toxin connected to a binding ligand such as an antibody or growth factor. These molecules bind to surface antigens (which internalize) and kill cells by catalytic inhibition of protein synthesis within the cell cytosol. Immunotoxins have recently been tested clinically in hematologic malignancies and solid tumors and have demonstrated potent clinical efficacy in patients with malignant diseases that are refractory to surgery, radiation therapy and chemotherapy - the traditional modalities of cancer treatment. This therapy is thus evolving into a separate modality of cancer treatment, capable of rationally targeting cells on the basis of surface markers. Efforts are underway to obviate impediments to clinical efficacy, including immunogenicity and toxicity to normal tissues. Immunotoxins are now being developed to new antigens for the treatment of cancer. JF - Current opinion in immunology AU - Kreitman, R J AD - Laboratory of Molecular Biology, Division of Cancer Biology, National Cancer Institute, National Institutes of Health, 37/4B27, 9000 Rockville Pike, 4255 Bethesda, MD 20892, USA. kreitmar@mail.nih.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 570 EP - 578 VL - 11 IS - 5 SN - 0952-7915, 0952-7915 KW - Antineoplastic Agents KW - 0 KW - Bacterial Toxins KW - Biomarkers, Tumor KW - Diphtheria Toxin KW - Exotoxins KW - Immunotoxins KW - Receptors, Cell Surface KW - Recombinant Fusion Proteins KW - Virulence Factors KW - Ricin KW - 9009-86-3 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Receptors, Cell Surface -- immunology KW - Biomarkers, Tumor -- immunology KW - Humans KW - Clinical Trials as Topic KW - Recombinant Fusion Proteins -- therapeutic use KW - Neoplasms -- drug therapy KW - Immunotoxins -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70797037?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+immunology&rft.atitle=Immunotoxins+in+cancer+therapy.&rft.au=Kreitman%2C+R+J&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1999-10-01&rft.volume=11&rft.issue=5&rft.spage=570&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+immunology&rft.issn=09527915&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-15 N1 - Date created - 1999-11-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1 oncoprotein. AN - 70792936; 10508522 AB - Chromosomal translocations resulting in the expression of chimaeric transcription factors are frequently observed in tumour cells, and have been suggested to be a common mechanism in human carcinogenesis. Ewing sarcoma and related peripheral primitive neuroectodermal tumours share recurrent translocations that fuse the gene EWSR1 (formerly EWS) from 22q-12 to FLI1 and genes encoding other ETS transcription factors (which bind DNA through the conserved ETS domain). It has been shown that transduction of the gene EWSR1-FLI1 (encoding EWS-FLI1 protein) can transform NIH3T3 cells, and that mutants containing a deletion in either the EWS domain or the DNA-binding domain in FLI1 lose this ability. This indicates that the EWS-FLI1 fusion protein may act as an aberrant transcription factor, but the exact mechanism of oncogenesis remains unknown. Because ETS transcription factors regulate expression of TGFBR2 (encoding the TGF-beta type II receptor, TGF-beta RII; Refs 9,14), a putative tumour suppressor gene, we hypothesized that TGFBR2 may be a target of the EWS-FLI1 fusion protein. We show here that Ewing sarcoma [corrected] (ES) cell lines with the EWSR1-FLI1 fusion have reduced TGF-beta sensitivity, and that fusion-positive ES cells and primary tumours both express low or undetectable levels of TGFBR2 mRNA and protein product. Co-transfection of FLI1 and the TGFBR2 promoter induces promoter activity, whereas EWSR1-FLI1 leads to suppression of TGFBR2 promoter activity and FLI1-induced promoter activity. Introduction of EWSR1-FLI1 into cells lacking the EWSR1-FLI1 fusion suppresses TGF-beta RII expression, whereas antisense to EWSR1-FLI1 in ES cell lines positive for this gene fusion restores TGF-beta RII expression. Furthermore, introduction of normal TGF-beta RII into ES cell lines restores TGF-beta sensitivity and blocks tumorigenicity. Our results implicate TGF-beta RII as a direct target of EWS-FLI1. JF - Nature genetics AU - Hahm, K B AU - Cho, K AU - Lee, C AU - Im, Y H AU - Chang, J AU - Choi, S G AU - Sorensen, P H AU - Thiele, C J AU - Kim, S J AD - Laboratory of Cell Regulation, DBS, National Cancer Institute, Bethesda, Maryland 20892-5055, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 222 EP - 227 VL - 23 IS - 2 SN - 1061-4036, 1061-4036 KW - DNA-Binding Proteins KW - 0 KW - EWS-FLI fusion protein KW - Fli1 protein, mouse KW - Oncogene Proteins, Fusion KW - Proto-Oncogene Protein c-fli-1 KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - RNA-Binding Protein EWS KW - Receptors, Transforming Growth Factor beta KW - Recombinant Fusion Proteins KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - Luciferases KW - EC 1.13.12.- KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Neuroblastoma -- pathology KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - DNA-Binding Proteins -- genetics KW - Mice, Nude KW - RNA, Messenger -- genetics KW - Recombinant Fusion Proteins -- metabolism KW - Sarcoma, Ewing -- pathology KW - Trans-Activators -- genetics KW - Recombinant Fusion Proteins -- genetics KW - Gene Expression Regulation -- drug effects KW - Promoter Regions, Genetic -- genetics KW - Luciferases -- genetics KW - Sequence Deletion KW - Sarcoma, Ewing -- genetics KW - Tumor Cells, Cultured -- metabolism KW - Luciferases -- metabolism KW - Sarcoma, Ewing -- metabolism KW - Mice KW - Neuroblastoma -- metabolism KW - Neuroblastoma -- genetics KW - RNA, Messenger -- metabolism KW - Transfection KW - Immunohistochemistry KW - Cell Line KW - Transcription Factors -- physiology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Oncogene Proteins, Fusion -- physiology KW - Oncogene Proteins, Fusion -- genetics KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70792936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Repression+of+the+gene+encoding+the+TGF-beta+type+II+receptor+is+a+major+target+of+the+EWS-FLI1+oncoprotein.&rft.au=Hahm%2C+K+B%3BCho%2C+K%3BLee%2C+C%3BIm%2C+Y+H%3BChang%2C+J%3BChoi%2C+S+G%3BSorensen%2C+P+H%3BThiele%2C+C+J%3BKim%2C+S+J&rft.aulast=Hahm&rft.aufirst=K&rft.date=1999-10-01&rft.volume=23&rft.issue=2&rft.spage=222&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Nat Genet 1999 Dec;23(4):481 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ovariectomy increases squamous metaplasia of the uterine horns and survival of SENCAR mice fed a vitamin A-deficient diet. AN - 70791659; 10500019 AB - Retinoic acid is necessary for the growth and differentiation of organisms and exerts its molecular actions by binding to specific nuclear receptors that belong to the thyroid-steroid hormone receptor superfamily. Steroids and retinoids control the differentiation of the female reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia. Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival. We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 microg retinoic acid/g diet. Mice were either ovariectomized or intact. Squamous cells arising in the normally simple columnar epithelium of the endocervix and uterine cavity were monitored by keratin 5 expression with immunohistochemistry. Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%. Factors other than epithelial differentiation per se control survival outcome of vitamin A-deficient mice. The results also show a significant increase in longevity of vitamin A- deficient mice when ovariectomized. JF - The American journal of clinical nutrition AU - Ponnamperuma, R M AU - Kirchhof, S M AU - Trifiletti, L AU - De Luca, L M AD - Differentiation Control Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 502 EP - 508 VL - 70 IS - 4 SN - 0002-9165, 0002-9165 KW - Keratins KW - 68238-35-7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Metaplasia KW - Mice KW - Mice, Inbred SENCAR KW - Keratins -- analysis KW - Epithelium -- pathology KW - Immunohistochemistry KW - Female KW - Ovariectomy -- adverse effects KW - Vitamin A Deficiency -- pathology KW - Uterus -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70791659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Ovariectomy+increases+squamous+metaplasia+of+the+uterine+horns+and+survival+of+SENCAR+mice+fed+a+vitamin+A-deficient+diet.&rft.au=Ponnamperuma%2C+R+M%3BKirchhof%2C+S+M%3BTrifiletti%2C+L%3BDe+Luca%2C+L+M&rft.aulast=Ponnamperuma&rft.aufirst=R&rft.date=1999-10-01&rft.volume=70&rft.issue=4&rft.spage=502&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-20 N1 - Date created - 1999-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Disruption of the mouse necdin gene results in early post-natal lethality. AN - 70791275; 10508517 AB - Prader-Willi syndrome (PWS) is a neurobehavioural disorder characterized by neonatal respiratory depression, hypotonia and failure to thrive in infancy, followed by hyperphagia and obesity among other symptoms. PWS is caused by the loss of one or more paternally expressed genes on chromosome 15q11-q13, which can be due to gene deletions, maternal uniparental disomy or mutations disrupting the imprinting mechanism. Imprinted genes mapped to this region include SNRPN (refs 3,4), ZNF127 (ref. 5), IPW (ref. 6) and NDN (which encodes the DNA-binding protein necdin; refs 7,8,9,10). The mouse homologues of these genes map to mouse chromosome 7 in a region syntenic with human chromosome 15q11-q13 (refs 7,11). Imprinting of the human genes is under the control of an imprinting center (IC), a long-range, cis-acting element located in the 5' region of SNRPN (ref. 12). A related control element was isolated in the mouse Snrpn genomic region which, when deleted on the paternally inherited chromosome, resulted in the loss of expression of all four genes and early post-natal lethality. To determine the possible contribution of Ndn to the PWS phenotype, we generated Ndn mutant mice. Heterozygous mice inheriting the mutated maternal allele were indistinguishable from their wild-type littermates. Mice carrying a paternally inherited Ndn deletion allele demonstrated early post-natal lethality. This is the first example of a single gene being responsible for phenotypes associated with PWS. JF - Nature genetics AU - Gérard, M AU - Hernandez, L AU - Wevrick, R AU - Stewart, C L AD - Cancer and Developmental Biology Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 199 EP - 202 VL - 23 IS - 2 SN - 1061-4036, 1061-4036 KW - Nerve Tissue Proteins KW - 0 KW - Nuclear Proteins KW - necdin KW - Index Medicus KW - Animals KW - Mice KW - Tissue Distribution KW - Embryo, Mammalian -- metabolism KW - Phenotype KW - Mutagenesis, Site-Directed KW - Genotype KW - Mice, Inbred Strains KW - Animals, Newborn KW - Mice, Mutant Strains KW - Alleles KW - Survival Rate KW - Embryonic and Fetal Development KW - Mice, Inbred C57BL KW - Mice, Inbred C3H KW - Crosses, Genetic KW - Female KW - Gene Expression Regulation, Developmental KW - Male KW - Nuclear Proteins -- genetics KW - Nerve Tissue Proteins -- metabolism KW - Prader-Willi Syndrome -- pathology KW - Prader-Willi Syndrome -- genetics KW - Nuclear Proteins -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Prader-Willi Syndrome -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70791275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+genetics&rft.atitle=Disruption+of+the+mouse+necdin+gene+results+in+early+post-natal+lethality.&rft.au=G%C3%A9rard%2C+M%3BHernandez%2C+L%3BWevrick%2C+R%3BStewart%2C+C+L&rft.aulast=G%C3%A9rard&rft.aufirst=M&rft.date=1999-10-01&rft.volume=23&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Nature+genetics&rft.issn=10614036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Genet. 1999 Oct;23(2):132-4 [10508501] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the RhoA pathway in human endothelial cell spreading on type IV collagen: role of calcium influx. AN - 70790386; 10504326 AB - We have shown that nonvoltage-operated Ca(2+) entry regulates human umbilical vein endothelial cell adhesion, migration, and proliferation on type IV collagen. We now demonstrate a requirement for Ca(2+) influx for activation of the RhoA pathway during endothelial cell spreading on type IV collagen. Reorganization of actin into stress fibers was complete when the cells where fully spread at 90 minutes. No actin organization into stress fibers was seen in endothelial cells plated on type I collagen, indicating a permissive effect of type IV collagen. CAI, a blocker of nonvoltage-operated Ca(2+) channels, prevented development of stress fiber formation in endothelial cells on type IV collagen. This permissive effect was augmented by Ca(2+) influx, as stimulated by 0. 5 microM thapsigargin or 0.1 microM ionomycin, yielding faster development of actin stress fibers. Ca(2+) influx and actin rearrangement in response to thapsigargin and ionomycin were abrogated by CAI. Activated, membrane-bound RhoA is a substrate for C3 exoenzyme which ADP-ribosylates and inactivates RhoA, preventing actin stress fiber formation. Pretreatment of endothelial cells with C3 exoenzyme prevented basal and thapsigargin-augmented stress fiber formation. While regulation of Ca(2+) influx did not alter RhoA translocation, it reduced in vitro ADP-ribosylation of RhoA (P(2)<0. 05), suggesting Ca(2+) influx is needed for RhoA activation during spreading on type IV collagen; no Ca(2+) regulated change in RhoA was seen in HUVECs spreading on type I collagen matrix. Blockade of Ca(2+) influx of HUVEC spread on type IV collagen also reduced tyrosine phosphorylation of p190Rho-GAP and blocked thapsigargin-enhanced binding of p190Rho-GAP to focal adhesion kinase. Thus, Ca(2+) influx is necessary for RhoA activation and for linkage of the RhoA/stress fiber cascade to the focal adhesion/focal adhesion kinase pathway during human umbilical vein endothelial cell spreading on type IV collagen. JF - Journal of cell science AU - Masiero, L AU - Lapidos, K A AU - Ambudkar, I AU - Kohn, E C AD - Molecular Signaling Section, Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 3205 EP - 3213 VL - 112 ( Pt 19) SN - 0021-9533, 0021-9533 KW - ARHGAP35 protein, human KW - 0 KW - Actins KW - Cell Adhesion Molecules KW - Enzyme Inhibitors KW - Guanine Nucleotide Exchange Factors KW - Nuclear Proteins KW - Phosphoproteins KW - Repressor Proteins KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Tyrosine KW - 42HK56048U KW - Thapsigargin KW - 67526-95-8 KW - Collagen KW - 9007-34-5 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - exoenzyme C3, Clostridium botulinum KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Focal Adhesion Kinase 1 KW - EC 2.7.10.2 KW - Focal Adhesion Protein-Tyrosine Kinases KW - PTK2 protein, human KW - Botulinum Toxins KW - EC 3.4.24.69 KW - rhoA GTP-Binding Protein KW - EC 3.6.5.2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Space life sciences KW - Nuclear Proteins -- isolation & purification KW - Cell Adhesion -- physiology KW - Humans KW - Umbilical Veins -- cytology KW - Actins -- metabolism KW - Cytoskeleton -- physiology KW - Adenosine Diphosphate Ribose -- metabolism KW - ADP Ribose Transferases -- pharmacology KW - Cytoskeleton -- drug effects KW - Calcium -- metabolism KW - Phosphorylation KW - Stress, Mechanical KW - Cytoskeleton -- chemistry KW - Cell Adhesion Molecules -- metabolism KW - Tyrosine -- metabolism KW - Biological Transport -- physiology KW - Nuclear Proteins -- metabolism KW - Phosphoproteins -- isolation & purification KW - Cell Adhesion Molecules -- isolation & purification KW - Neovascularization, Physiologic -- physiology KW - Phosphoproteins -- metabolism KW - Pseudopodia -- physiology KW - Protein-Tyrosine Kinases -- isolation & purification KW - Protein-Tyrosine Kinases -- metabolism KW - Precipitin Tests KW - Biological Transport -- drug effects KW - Thapsigargin -- pharmacology KW - Cells, Cultured KW - Kinetics KW - Enzyme Inhibitors -- pharmacology KW - Cell Adhesion -- drug effects KW - rhoA GTP-Binding Protein -- metabolism KW - Calcium Signaling -- drug effects KW - Endothelium, Vascular -- enzymology KW - Endothelium, Vascular -- cytology KW - Collagen -- metabolism KW - Calcium Signaling -- physiology KW - Collagen -- pharmacology KW - rhoA GTP-Binding Protein -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70790386?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=Regulation+of+the+RhoA+pathway+in+human+endothelial+cell+spreading+on+type+IV+collagen%3A+role+of+calcium+influx.&rft.au=Masiero%2C+L%3BLapidos%2C+K+A%3BAmbudkar%2C+I%3BKohn%2C+E+C&rft.aulast=Masiero&rft.aufirst=L&rft.date=1999-10-01&rft.volume=112+%28+Pt+19%29&rft.issue=&rft.spage=3205&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-17 N1 - Date created - 1999-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - National Institutes of Health workshop: role of nutrient regulation of signal transduction in metabolic diseases. AN - 70789560; 10500024 JF - The American journal of clinical nutrition AU - Kim, S K Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 544 VL - 70 IS - 4 KW - Leptin KW - 0 KW - Peroxisome Proliferators KW - Proteins KW - Transcription Factors KW - Abridged Index Medicus KW - Index Medicus KW - Peroxisome Proliferators -- metabolism KW - Humans KW - Gene Expression Regulation KW - Transcription Factors -- genetics KW - Proteins -- physiology KW - Signal Transduction -- physiology KW - Metabolic Diseases -- physiopathology KW - Nutritional Physiological Phenomena -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70789560?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=National+Institutes+of+Health+workshop%3A+role+of+nutrient+regulation+of+signal+transduction+in+metabolic+diseases.&rft.au=Kim%2C+S+K&rft.aulast=Kim&rft.aufirst=S&rft.date=1999-10-01&rft.volume=70&rft.issue=4&rft.spage=544&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-20 N1 - Date created - 1999-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroendocrine host factors and inflammatory disease susceptibility. AN - 70789464; 10502534 AB - The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. JF - Environmental health perspectives AU - Ligier, S AU - Sternberg, E M AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1284, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 701 EP - 707 VL - 107 Suppl 5 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - Rats KW - Stress, Physiological -- complications KW - Animals KW - Chickens KW - Sjogren's Syndrome -- etiology KW - Humans KW - Autoimmune Diseases -- etiology KW - Arthritis, Rheumatoid -- etiology KW - Environmental Exposure KW - Disease Models, Animal KW - Mice KW - Lupus Erythematosus, Systemic -- etiology KW - Neurosecretory Systems -- immunology KW - Inflammation -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70789464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Neuroendocrine+host+factors+and+inflammatory+disease+susceptibility.&rft.au=Ligier%2C+S%3BSternberg%2C+E+M&rft.aulast=Ligier&rft.aufirst=S&rft.date=1999-10-01&rft.volume=107+Suppl+5&rft.issue=&rft.spage=701&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-28 N1 - Date created - 2000-08-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Rheumatol. 1995 Nov;22(11):2084-91 [8596149] Horm Res. 1995;44(5):208-12 [8582712] Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2359-64 [8637878] Brain Res Brain Res Rev. 1997 Feb;23(1-2):79-133 [9063588] J Neurosci. 1997 May 1;17(9):3234-8 [9157197] J Clin Endocrinol Metab. 1997 Apr;82(4):1279-83 [9100607] J Endocrinol. 1997 May;153(2):185-91 [9166107] J Clin Endocrinol Metab. 1997 Jul;82(7):2182-91 [9215292] Exp Neurol. 1997 Aug;146(2):305-14 [9270039] Ann N Y Acad Sci. 1998 May 1;840:599-607 [9629287] Ann N Y Acad Sci. 1998 May 1;840:698-704 [9629296] Ann N Y Acad Sci. 1998 May 1;840:762-72 [9629303] J Rheumatol. 1998 Jun;25(6):1097-103 [9632070] Ann N Y Acad Sci. 1998 Jun 30;851:477-86 [9668641] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9979-84 [9707586] J Rheumatol. 1998 Aug;25(8):1508-14 [9712092] Environ Health Perspect. 1998 Sep;106(9):523-9 [9721252] Lupus. 1998;7(6):404-8 [9736324] Lupus. 1998;7(6):414-9 [9736326] Br J Rheumatol. 1996 Apr;35(4):350-6 [8624638] J Am Acad Child Adolesc Psychiatry. 1996 Jun;35(6):764-73 [8682757] J Rheumatol. 1996 Apr;23(4):577-81 [8730107] Prog Brain Res. 1996;107:201-22 [8782521] Nat Genet. 1996 Sep;14(1):82-5 [8782824] Immunol Today. 1996 Mar;17(3):138-46 [8820272] Neuroimmunomodulation. 1995 Nov-Dec;2(6):329-38 [8840335] Proc Assoc Am Physicians. 1996 Sep;108(5):374-81 [8902882] Neuroimmunomodulation. 1996 Mar-Jun;3(2-3):93-101 [8945724] Brain Behav Immun. 1996 Dec;10(4):337-50 [9045749] Ann N Y Acad Sci. 1997 Aug 14;823:214-24 [9292047] J Neuroimmunol. 1997 Oct;79(1):22-8 [9357443] J Clin Invest. 1997 Dec 1;100(11):2641-7 [9389725] J Rheumatol. 1997 Dec;24(12):2330-4 [9415637] J Rheumatol. 1998 Jan;25(1):16-22 [9458197] Proc Soc Exp Biol Med. 1998 Apr;217(4):408-19 [9521087] J Neuroimmunol. 1998 Jan;81(1-2):144-57 [9521616] Curr Opin Rheumatol. 1998 May;10(3):187-200 [9608321] Ann N Y Acad Sci. 1998 May 1;840:21-32 [9629233] Ann N Y Acad Sci. 1998 May 1;840:45-50 [9629235] Ann N Y Acad Sci. 1998 May 1;840:262-8 [9629254] Ann N Y Acad Sci. 1998 May 1;840:282-8 [9629256] Ann N Y Acad Sci. 1998 May 1;840:591-8 [9629286] Lupus. 1998;7(6):420-7 [9736327] Am J Physiol. 1998 Oct;275(4 Pt 2):R1247-55 [9756557] J Dermatol. 1998 Aug;25(8):558-60 [9769607] Acta Derm Venereol. 1998 Nov;78(6):420-3 [9833039] Mamm Genome. 1999 Apr;10(4):362-5 [10087293] J Clin Endocrinol Metab. 1953 Sep;13(9):1118-21 [13084730] Clin Chim Acta. 1970 Jul;29(1):129-37 [5533427] Br Med J (Clin Res Ed). 1982 Feb 20;284(6315):551-4 [6800538] Science. 1985 Oct 18;230(4723):325-7 [4048936] Br J Pharmacol. 1986 Jan;87(1):57-62 [3006856] Clin Exp Rheumatol. 1986 Oct-Dec;4(4):365-6 [3791721] J Clin Invest. 1987 Apr;79(4):1160-71 [3494045] J Steroid Biochem. 1988;30(1-6):375-9 [3260312] J Exp Med. 1989 Feb 1;169(2):431-45 [2783450] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2374-8 [2538840] Proc Natl Acad Sci U S A. 1989 Jun;86(12):4771-5 [2786636] N Engl J Med. 1990 Mar 29;322(13):874-81 [1690352] Arch Gen Psychiatry. 1990 Apr;47(4):325-30 [2157379] J Clin Invest. 1990 Nov;86(5):1757-63 [2243145] Endocrinology. 1992 Mar;130(3):1394-400 [1537299] JAMA. 1992 Mar 4;267(9):1244-52 [1538563] Arthritis Rheum. 1992 Jul;35(7):740-4 [1622411] Ann Intern Med. 1992 Nov 15;117(10):854-66 [1416562] Arthritis Rheum. 1992 Nov;35(11):1281-8 [1445443] Gen Comp Endocrinol. 1992 Nov;88(2):188-98 [1335939] Endocrinology. 1993 Mar;132(3):1313-8 [8382598] Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3383-7 [8475085] Lupus. 1992 May;1(3):191-5 [1301981] Am J Med. 1993 Dec;95(6):637-44 [8259781] J Neuroimmunol. 1994 Jan;49(1-2):67-75 [8294563] J Neuroimmunol. 1994 Jan;49(1-2):77-87 [8294564] J Autoimmun. 1993 Dec;6(6):719-33 [8155253] Arthritis Rheum. 1994 Aug;37(8):1127-31 [8053950] Arthritis Rheum. 1994 Aug;37(8):1132-7 [8053951] J Clin Endocrinol Metab. 1994 Sep;79(3):848-53 [8077372] Gastroenterology. 1994 Nov;107(5):1469-74 [7926509] Semin Arthritis Rheum. 1994 Aug;24(1):19-28 [7985034] C R Acad Sci III. 1994 Jun;317(6):499-503 [7987701] Neurology. 1994 Dec;44(12):2289-94 [7991114] Neurology. 1994 Dec;44(12):2390-2 [7991132] Ann N Y Acad Sci. 1994 Nov 30;746:327-35 [7825886] N Engl J Med. 1995 May 18;332(20):1351-62 [7715646] Neurosci Lett. 1995 Jan 2;183(1-2):27-31 [7746479] Endocrinology. 1995 Jul;136(7):3107-12 [7789338] N Engl J Med. 1995 Jul 20;333(3):142-6 [7791815] Endocrinology. 1995 Aug;136(8):3299-309 [7628364] Int Rev Immunol. 1995;12(2-4):201-16 [7544386] Br Med Bull. 1995 Apr;51(2):368-84 [7552070] J Rheumatol. 1995 Oct;22(10):1829-33 [8991978] Am J Psychiatry. 1996 Jan;153(1):69-73 [8540595] J Clin Endocrinol Metab. 1996 Jan;81(1):228-35 [8550757] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medicinal herbs in the United States: research needs. AN - 70789303; 10504141 AB - Virtually all cultures have, throughout history, used a variety of plants or materials derived from plants for the prevention and treatment of disease. Evidence of the beneficial therapeutic effects of these medicinal herbs is seen in their continued use. Additionally, the development of modern chemistry permitted the isolation of chemicals from medicinal herbs that have served as drugs or starting materials for the synthesis of many important drugs used today. Many more modern drugs have been synthesized as a result of knowledge gained from studies of mechanisms of actions of chemicals first isolated from medicinal herbs. Thus, medicinal herbs have played a major role in the development of modern medicine and continue to be widely used in their original form. Whereas it is generally agreed that most medicinal herbs are safe under the conditions used, some are toxic and should be avoided even though they are readily available, and others have significant adverse side effects when misused. Also, little has been done to investigate potential adverse effects that may be associated with extended or high-dose use of medicinal herbs. Thus, concern has been expressed that the lack of quality control used in the preparation of medicinal herbs, plus their unregulated sale and uninformed use, pose potential adverse health effects for consumers. There is also concern regarding potential herb/herb or herb/drug interactions and possible untoward health effects of medicinal herbs in sensitive subpopulations such as the young and the elderly and certain genetically predisposed individuals. In this paper, we discuss these concerns at some length and make recommendations for additional research and education discussed in the recent International Workshop to Evaluate Research Needs on the Use and Safety of Medicinal Herbs. JF - Environmental health perspectives AU - Matthews, H B AU - Lucier, G W AU - Fisher, K D AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA. matthews@niehs.nih.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 773 EP - 778 VL - 107 IS - 10 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - United States KW - Patient Education as Topic KW - Drug Interactions KW - Humans KW - Dietary Supplements KW - Phytotherapy KW - Plants, Medicinal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70789303?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Medicinal+herbs+in+the+United+States%3A+research+needs.&rft.au=Matthews%2C+H+B%3BLucier%2C+G+W%3BFisher%2C+K+D&rft.aulast=Matthews&rft.aufirst=H&rft.date=1999-10-01&rft.volume=107&rft.issue=10&rft.spage=773&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-02 N1 - Date created - 1999-12-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: N Engl J Med. 1998 Sep 17;339(12):839-41 [9738094] JAMA. 1998 Nov 11;280(18):1616-8 [9820266] Arch Intern Med. 1998 Nov 9;158(20):2200-11 [9818800] JAMA. 1998 Nov 11;280(18):1618-9 [9820267] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. AN - 70789148; 10496959 AB - We investigated the effect of resveratrol, a constituent of the human diet that has been shown to inhibit aryl hydrocarbon-induced carcinogenesis in animals, on the carcinogen activation pathway regulated by the aryl hydrocarbon receptor. Resveratrol inhibited the metabolism of the environmental aryl hydrocarbon benzo[a]pyrene (B[a]P) catalyzed by microsomes isolated from B[a]P-treated human hepatoma HepG2 cells. Resveratrol competitively inhibited, in a concentration-dependent manner, the activity of the carcinogen activating enzymes cytochrome P-450 (CYP)1A1/CYP1A2 in microsomes and intact HepG2 cells. Resveratrol inhibited the B[a]P-induced expression of the CYP1A1 gene, as measured at the mRNA and transcriptional levels. Resveratrol abolished the binding of B[a]P-activated nuclear aryl hydrocarbon receptor to the xenobiotic-responsive element of the CYP1A1 promoter but did not itself bind to the receptor. Resveratrol was also effective in inhibiting CYP1A1 transcription induced by the aryl hydrocarbon dimethylbenz[a]anthracene in human mammary carcinoma MCF-7 cells. These data demonstrate that resveratrol inhibits aryl hydrocarbon-induced CYP1A activity in vitro by directly inhibiting CYP1A1/1A2 enzyme activity and by inhibiting the signal transduction pathway that up-regulates the expression of carcinogen activating enzymes. These activities may be an important part of the chemopreventive activity of resveratrol in vivo. JF - Molecular pharmacology AU - Ciolino, H P AU - Yeh, G C AD - Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201, USA. hciolino@mail.ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 760 EP - 767 VL - 56 IS - 4 SN - 0026-895X, 0026-895X KW - Anticarcinogenic Agents KW - 0 KW - Carcinogens KW - Enzyme Inhibitors KW - Receptors, Aryl Hydrocarbon KW - Stilbenes KW - Benzo(a)pyrene KW - 3417WMA06D KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - resveratrol KW - Q369O8926L KW - Index Medicus KW - Gene Expression -- drug effects KW - Carcinogens -- pharmacology KW - Tumor Cells, Cultured KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacology KW - Enzyme Activation KW - Humans KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Benzo(a)pyrene -- metabolism KW - Cytochrome P-450 CYP1A1 -- genetics KW - Stilbenes -- pharmacology KW - Anticarcinogenic Agents -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Cytochrome P-450 CYP1A1 -- antagonists & inhibitors KW - Cytochrome P-450 CYP1A1 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70789148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Inhibition+of+aryl+hydrocarbon-induced+cytochrome+P-450+1A1+enzyme+activity+and+CYP1A1+expression+by+resveratrol.&rft.au=Ciolino%2C+H+P%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1999-10-01&rft.volume=56&rft.issue=4&rft.spage=760&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-08 N1 - Date created - 1999-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Safety and efficacy of multilamellar liposomal nystatin against disseminated candidiasis in persistently neutropenic rabbits. AN - 70784783; 10508025 AB - The activity of liposomal nystatin (L-Nys) against subacute disseminated candidiasis was investigated in persistently neutropenic rabbits. Antifungal therapy was administered for 10 days starting 24 h after intravenous inoculation of 10(3) blastoconidia of Candida albicans. Responses to treatment were assessed by the quantitative clearance of the organism from blood and tissues. Treatments consisted of L-Nys at dosages of 2 and 4 mg/kg of body weight/day (L-Nys2 and L-Nys4, respectively) amphotericin B deoxycholate at 1 mg/kg/day (D-AmB), and fluconazole at 10 mg/kg/day (Flu). All treatments were given intravenously once daily. Compared to the results for untreated but infected control animals, treatment with L-Nys2, L-Nys4, D-AmB, and Flu resulted in a significant clearance of the residual burden of C. albicans from the kidney, liver, spleen, lung, and brain (P < 0.0001 by analysis of variance). When the proportion of animals infected at at least one of the five tissue sites studied was evaluated, a dose-dependent response to treatment with L-Nys was found (P < 0.05). Compared to D-AmB-treated rabbits, mean serum creatinine and blood urea nitrogen levels at the end of therapy were significantly lower in animals treated with L-Nys2 (P < 0.001) and L-Nys4 (P < 0.001 and P < 0.01, respectively). L-Nys was less nephrotoxic than conventional amphotericin B and had dose-dependent activity comparable to that of amphotericin B for the early treatment of subacute disseminated candidiasis in persistently neutropenic rabbits. JF - Antimicrobial agents and chemotherapy AU - Groll, A H AU - Petraitis, V AU - Petraitiene, R AU - Field-Ridley, A AU - Calendario, M AU - Bacher, J AU - Piscitelli, S C AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 2463 EP - 2467 VL - 43 IS - 10 SN - 0066-4804, 0066-4804 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Nystatin KW - 1400-61-9 KW - Amphotericin B KW - 7XU7A7DROE KW - Fluconazole KW - 8VZV102JFY KW - Index Medicus KW - Animals KW - Fluconazole -- therapeutic use KW - Treatment Outcome KW - Disease Models, Animal KW - Rabbits KW - Amphotericin B -- therapeutic use KW - Nystatin -- toxicity KW - Candidiasis -- drug therapy KW - Antifungal Agents -- toxicity KW - Nystatin -- administration & dosage KW - Antifungal Agents -- administration & dosage KW - Nystatin -- therapeutic use KW - Candidiasis -- etiology KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70784783?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Safety+and+efficacy+of+multilamellar+liposomal+nystatin+against+disseminated+candidiasis+in+persistently+neutropenic+rabbits.&rft.au=Groll%2C+A+H%3BPetraitis%2C+V%3BPetraitiene%2C+R%3BField-Ridley%2C+A%3BCalendario%2C+M%3BBacher%2C+J%3BPiscitelli%2C+S+C%3BWalsh%2C+T+J&rft.aulast=Groll&rft.aufirst=A&rft.date=1999-10-01&rft.volume=43&rft.issue=10&rft.spage=2463&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-13 N1 - Date created - 1999-12-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Infect Dis. 1992 Apr;14(4):875-83 [1576282] N Engl J Med. 1992 Mar 26;326(13):845-51 [1542320] Bone Marrow Transplant. 1993 Jun;11(6):465-70 [8334427] Clin Infect Dis. 1992 Mar;14 Suppl 1:S120-5 [1562683] Clin Infect Dis. 1992 Mar;14 Suppl 1:S139-47 [1562687] Diagn Microbiol Infect Dis. 1993 Aug-Sep;17(2):103-9 [8243032] J Infect. 1996 Jul;33(1):23-32 [8842991] Clin Infect Dis. 1997 Jul;25(1):43-59 [9243032] Antimicrob Agents Chemother. 1997 Sep;41(9):1871-5 [9303376] Antimicrob Agents Chemother. 1997 Oct;41(10):2238-43 [9333054] Adv Pharmacol. 1998;44:343-500 [9547888] Am J Med. 1998 Mar;104(3):238-45 [9552086] N Engl J Med. 1999 Mar 11;340(10):764-71 [10072411] J Antimicrob Chemother. 1999 Jan;43(1):95-103 [10381106] Science. 1950 Oct 13;112(2911):423 [14781786] Bone Marrow Transplant. 1996 Jun;17(6):1043-9 [8807112] J Chromatogr B Biomed Sci Appl. 1999 Nov 26;735(1):51-62 [10630890] Dermatol Int. 1967 Jul-Sep;6(3):154-60 [5590117] Bacteriol Rev. 1973 Sep;37(3):166-96 [4202146] J Membr Biol. 1984;80(3):257-69 [6094818] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Antimicrob Agents Chemother. 1987 Dec;31(12):1897-900 [3439798] Antimicrob Agents Chemother. 1987 Dec;31(12):1901-3 [3439799] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] J Infect Dis. 1990 Apr;161(4):755-60 [2138654] Cancer. 1991 Aug 1;68(3):594-9 [2065280] J Infect Dis. 1991 Oct;164(4):731-40 [1894935] Ann Intern Med. 1993 Apr 1;118(7):495-503 [8442620] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recurrent alterations of the short arm of chromosome 3 define a tumor suppressor region in rat mammary tumor cells. AN - 70777791; 10506121 AB - Cytogenetic alterations associated with different stages in carcinogenesis can be distinguished in cultured human or rodent cells transformed by carcinogenic agents. Three tumorigenic rat mammary epithelial cell lines transformed in vitro with 7,12, -dimethylbenz[a]anthracene alone or in combination with 12-O-tetradecanoylphorbol-13-acetate were examined cytogenetically. Non-random alterations consisting of translocations involving the short arm of chromosome 3 and trisomy of chromosomes 14 and X were identified in all three lines. Deletion and inversion of chromosome 1 with the breakpoint at band 1q22 and a duplication 1q 32-43 and trisomy of chromosome 2 were observed in two cell lines. The accumulation of structural alterations and chromosome imbalances during the process of cell immortalization and acquisition of tumorigenicity are required for normal rat mammary cells to become malignant. Unbalanced translocations of chromosome 3 resulting in loss of the short arm had the breakpoint at 3p11. This site is a hotspot of breakage and recombination in various rat tumors and may represent a region of tumor suppressor gene critical to the development of rat mammary tumors, as well as other types of tumors. JF - Carcinogenesis AU - Popescu, N C AU - Greiner, J W AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. popescun@dc37a.nci.nih.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 2033 EP - 2036 VL - 20 IS - 10 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Rats KW - Karyotyping KW - Animals KW - Rats, Sprague-Dawley KW - Tumor Cells, Cultured KW - Humans KW - Cell Line, Transformed KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Genes, Tumor Suppressor KW - Chromosome Aberrations KW - Mammary Neoplasms, Experimental -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70777791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Recurrent+alterations+of+the+short+arm+of+chromosome+3+define+a+tumor+suppressor+region+in+rat+mammary+tumor+cells.&rft.au=Popescu%2C+N+C%3BGreiner%2C+J+W&rft.aulast=Popescu&rft.aufirst=N&rft.date=1999-10-01&rft.volume=20&rft.issue=10&rft.spage=2033&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of D(1) dopamine receptors with mutations of protein kinase phosphorylation sites: attenuation of the rate of agonist-induced desensitization. AN - 70777406; 10496949 AB - Investigations of D(1) receptor regulation have suggested a role for cAMP-dependent protein kinase (PKA) in agonist-induced desensitization and down-regulation of receptor expression. Given the presence of at least four possible consensus recognition sites for PKA on the D(1) receptor protein, a reasonable hypothesis is that some of these PKA-mediated effects are caused by phosphorylation of the receptor. As an initial test of this hypothesis, we used site-directed mutagenesis to create a mutant D(1) receptor with substitutions at each of its four potential PKA phosphorylation sites. The modified amino acids are as follows: Thr135 to Val, Ser229 to Ala, Thr268 to Val, and Ser380 to Ala. Characterization of the wild-type and mutant receptors stably expressed in C6 glioma cells suggests that the mutations have no effect on receptor expression, antagonist or agonist affinities, or on functional coupling with respect to cAMP generation. Similarly, dopamine preincubation of the stably transfected C6 cells expressing either the wild-type or mutated D(1) receptors results in an agonist-induced loss of ligand binding activity (down-regulation) in an identical fashion. In contrast, the time of onset of dopamine-induced desensitization is greatly attenuated in the quadruple mutant receptor. After 1 h of dopamine pretreatment, the wild-type receptor exhibits approximately 80% desensitization of the cAMP response, whereas the mutant receptor is desensitized by only approximately 20%. Further analyses of single mutated receptors, in which only one of the four putative phosphorylation sites is modified, reveals that Thr268 in the third cytoplasmic loop of the receptor protein is primarily responsible for regulating the desensitization kinetics. These results are consistent with the hypothesis that phosphorylation of the D(1) receptor on Thr268 is important for rapid agonist-induced homologous desensitization. JF - Molecular pharmacology AU - Jiang, D AU - Sibley, D R AD - Molecular Neuropharmacology Section, Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 675 EP - 683 VL - 56 IS - 4 SN - 0026-895X, 0026-895X KW - Dopamine Agonists KW - 0 KW - Receptors, Dopamine D1 KW - Colforsin KW - 1F7A44V6OU KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Index Medicus KW - Rats KW - Animals KW - Colforsin -- pharmacology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Down-Regulation KW - Dopamine Agonists -- pharmacology KW - Point Mutation KW - Molecular Sequence Data KW - Cyclic AMP -- metabolism KW - Amino Acid Sequence KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Receptors, Dopamine D1 -- genetics KW - Receptors, Dopamine D1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70777406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Regulation+of+D%281%29+dopamine+receptors+with+mutations+of+protein+kinase+phosphorylation+sites%3A+attenuation+of+the+rate+of+agonist-induced+desensitization.&rft.au=Jiang%2C+D%3BSibley%2C+D+R&rft.aulast=Jiang&rft.aufirst=D&rft.date=1999-10-01&rft.volume=56&rft.issue=4&rft.spage=675&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-08 N1 - Date created - 1999-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glucuronidation of benzidine and its metabolites by cDNA-expressed human UDP-glucuronosyltransferases and pH stability of glucuronides. AN - 70776178; 10506112 AB - Although glucuronidation is considered a necessary step in aromatic amine-induced bladder cancer, the specific enzymes involved are not known. This study assessed the capacity of five different human recombinant UDP-glucuronosyltransferases expressed in COS-1 cells to glucuronidate benzidine, its metabolites and 4-aminobiphenyl. [(14)C]UDP-glucuronic acid was used as co-substrate. UGT1A1, UGT1A4 and UGT1A9 each metabolized all of the aromatic amines. UGT1A9 exhibited the highest relative rates of metabolism with preference for the two hydroxamic acids, N-hydroxy-N-acetylbenzidine and N-hydroxy-N,N'-diacetylbenzidine. UGT1A9 metabolized 4-aminobiphenyl approximately 50% faster than benzidine or N-acetylbenzidine. UGT1A4 N-glucuronidated N'-hydroxy- N-acetylbenzidine at the highest relative rate compared with the other transferases. UGT1A6 was effective in metabolizing only four of the eight aromatic amines tested. UGT1A1 demonstrated more extensive metabolism of the hydroxamic acid, N-hydroxy-N,N'-diacetylbenzidine, and the ring oxidation product, 3-OH-N,N'-diacetylbenzidine, than it did for the other six amines. UGT2B7 was the only product of the UGT2 gene family examined and it metabolized all the aromatic amines at similar low relative levels compared with a preferred substrate, 4-OH-estrone. The K(m) values for N-acetylbenzidine metabolism by UGT1A1 and UGT1A4 were 0.37 +/- 0.14 and 1.8 +/- 0.4 mM, respectively. The O-glucuronide of 3-OH-N,N'-diacetylbenzidine was not hydrolyzed during a 24 h 37 degrees C incubation at either pH 5. 5 or 7.4. Likewise, the O-glucuronide of 3-OH-benzidine was stable at pH 7.4, with 52% remaining at pH 5.5 after 24 h. These results suggest the following relative ranking of transferase metabolism: UGT1A9 > UGT1A4 > > UGT2B7 > UGT1A6 approximately UGT1A1. The relative pH stability of O-glucuronides is consistent with a role in detoxification and excretion of aromatic amines, while the acid lability of N-glucuronides is consistent with delivery of these amines to the bladder epithelium for activation, resulting in DNA adducts which may lead to mutations. JF - Carcinogenesis AU - Ciotti, M AU - Lakshmi, V M AU - Basu, N AU - Davis, B B AU - Owens, I S AU - Zenser, T V AD - Heritable Disorders Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 1963 EP - 1969 VL - 20 IS - 10 SN - 0143-3334, 0143-3334 KW - Benzidines KW - 0 KW - DNA Primers KW - DNA, Complementary KW - Glucuronides KW - Recombinant Proteins KW - benzidine KW - 2X02101HVF KW - Glucuronosyltransferase KW - EC 2.4.1.17 KW - Index Medicus KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Hydrogen-Ion Concentration KW - Humans KW - Enzyme Stability KW - Glucuronides -- metabolism KW - Benzidines -- metabolism KW - Glucuronosyltransferase -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70776178?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Glucuronidation+of+benzidine+and+its+metabolites+by+cDNA-expressed+human+UDP-glucuronosyltransferases+and+pH+stability+of+glucuronides.&rft.au=Ciotti%2C+M%3BLakshmi%2C+V+M%3BBasu%2C+N%3BDavis%2C+B+B%3BOwens%2C+I+S%3BZenser%2C+T+V&rft.aulast=Ciotti&rft.aufirst=M&rft.date=1999-10-01&rft.volume=20&rft.issue=10&rft.spage=1963&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular analysis of yeast and human type II topoisomerases. Enzyme-DNA and drug interactions. AN - 70764673; 10497180 AB - The DNA sequence selectivity of topoisomerase II (top2)-DNA cleavage complexes was examined for the human (top2alpha), yeast, and Escherichia coli (i.e. gyrase) enzymes in the absence or presence of anticancer or antibacterial drugs. Species-specific differences were observed for calcium-promoted DNA cleavage. Similarities and differences in DNA cleavage patterns and nucleic acid sequence preferences were also observed between the human, yeast, and E. coli top2 enzymes in the presence of the non-intercalators fluoroquinolone CP-115,953, etoposide, and azatoxin and the intercalators amsacrine and mitoxantrone. Additional base preferences were generally observed for the yeast when compared with the human top2alpha enzyme. Preferences in the immediate flanks of the top2-mediated DNA cleavage sites are, however, consistent with the drug stacking model for both enzymes. We also analyzed and compared homologous mutations in yeast and human top2, i.e. Ser(740) --> Trp and Ser(763) --> Trp, respectively. Both mutations decreased the reversibility of the etoposide-stabilized cleavage sites and produced consistent base sequence preference changes. These data demonstrate similarities and differences between human and yeast top2 enzymes. They also indicate that the structure of the enzyme/DNA interface plays a key role in determining the specificity of top2 poisons and cleavage sites for both the intercalating and non-intercalating drugs. JF - The Journal of biological chemistry AU - Strumberg, D AU - Nitiss, J L AU - Dong, J AU - Kohn, K W AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 28246 EP - 28255 VL - 274 IS - 40 SN - 0021-9258, 0021-9258 KW - Anti-Bacterial Agents KW - 0 KW - Anti-Infective Agents KW - Antineoplastic Agents KW - DNA Primers KW - DNA-Binding Proteins KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type II KW - EC 5.99.1.3 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Calcium -- metabolism KW - Base Sequence KW - Humans KW - Escherichia coli -- enzymology KW - Anti-Infective Agents -- metabolism KW - DNA Topoisomerases, Type II -- genetics KW - DNA -- metabolism KW - Antineoplastic Agents -- metabolism KW - DNA-Binding Proteins -- genetics KW - Saccharomyces cerevisiae -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70764673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Molecular+analysis+of+yeast+and+human+type+II+topoisomerases.+Enzyme-DNA+and+drug+interactions.&rft.au=Strumberg%2C+D%3BNitiss%2C+J+L%3BDong%2C+J%3BKohn%2C+K+W%3BPommier%2C+Y&rft.aulast=Strumberg&rft.aufirst=D&rft.date=1999-10-01&rft.volume=274&rft.issue=40&rft.spage=28246&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-02 N1 - Date created - 1999-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. AN - 70052144; 10493729 AB - In the CNS kainate subtype glutamate receptors (GluRs) are likely to be heteromeric assemblies containing multiple gene products. However, although recombinant kainate receptors from the GluR5-GluR7 gene family have been studied extensively in their homomeric forms, there have been no tests to determine whether these subunits can coassemble with each other. We used the GluR5 selective agonists (RS)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) and (S)-5-iodowillardiine (I-will) to test for the coassembly of GluR5 with GluR6 and GluR7 by measuring changes in rectification that occur for heteromeric receptors containing both edited and unedited Q/R site subunits. Birectifying ATPA and I-will responses resulting from polyamine block for homomeric GluR5(Q) became outwardly rectifying when GluR6(R) was coexpressed with GluR5(Q), although GluR6 was not activated by ATPA or I-will, indicating the formation of heteromeric receptors. Similar approaches showed the coassembly of GluR7 with GluR6 and GluR5. Heteromeric kainate receptors containing both GluR5 and GluR6 subunits exhibited novel functional properties, including reduced desensitization and faster recovery from desensitization than those recorded for homomeric GluR5. Coexpression of GluR6 with GluR5 also enhanced the magnitude of responses to GluR5 selective agonists. In contrast, the coassembly of GluR7 with GluR6 markedly decreased the amplitude of agonist responses. Our results indicate that, similar to AMPA receptors, the kainate receptor subunits GluR5-GluR7 exhibit promiscuous coassembly. The formation of heteromeric kainate receptors may help to explain why the functional properties of native kainate receptors differ from those that have been reported for recombinant kainate receptors. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Cui, C AU - Mayer, M L AD - Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 8281 EP - 8291 VL - 19 IS - 19 KW - 5-iodowillardiine KW - 0 KW - Excitatory Amino Acid Agonists KW - GluK3 kainate receptor KW - Gluk1 kainate receptor KW - Gluk2 kainate receptor KW - Isoxazoles KW - Macromolecular Substances KW - Propionates KW - Pyrimidines KW - Receptors, Kainic Acid KW - Recombinant Proteins KW - alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate KW - 140158-50-5 KW - Alanine KW - OF5P57N2ZX KW - Kainic Acid KW - SIV03811UC KW - Index Medicus KW - Genetic Variation KW - Kainic Acid -- pharmacology KW - Recombinant Proteins -- biosynthesis KW - Humans KW - Propionates -- pharmacology KW - Pyrimidines -- pharmacology KW - Mutagenesis, Site-Directed KW - Alanine -- analogs & derivatives KW - Alternative Splicing KW - Excitatory Amino Acid Agonists -- pharmacology KW - Membrane Potentials -- drug effects KW - Isoxazoles -- pharmacology KW - Alanine -- pharmacology KW - Cell Line KW - Receptors, Kainic Acid -- chemistry KW - Receptors, Kainic Acid -- genetics KW - Receptors, Kainic Acid -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70052144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Heteromeric+kainate+receptors+formed+by+the+coassembly+of+GluR5%2C+GluR6%2C+and+GluR7.&rft.au=Cui%2C+C%3BMayer%2C+M+L&rft.aulast=Cui&rft.aufirst=C&rft.date=1999-10-01&rft.volume=19&rft.issue=19&rft.spage=8281&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-14 N1 - Date created - 1999-10-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of various serotonin agonists, antagonists, and uptake inhibitors on the discriminative stimulus effects of methamphetamine in rats. AN - 70044955; 10490910 AB - Neurochemical studies indicate that methamphetamine increases central serotonin (5-HT) levels more markedly than other psychomotor stimulants such as amphetamine or cocaine. In the present study, we investigated 5-HT involvement in the discriminative stimulus effects of methamphetamine. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine i.p. from saline under a fixed-ratio schedule of food presentation, the effects of selected 5-HT agonists, antagonists, and uptake inhibitors were tested. Fluoxetine (1.8-18.0 mg/kg) and clomipramine (3.0-18.0 mg/kg), selective serotonin uptake inhibitors, did not produce any methamphetamine-like discriminative stimulus effects when administered alone, but fluoxetine (5.6 mg/kg), unlike clomipramine (5.6 mg/kg), significantly shifted the methamphetamine dose-response curve to the left. Both 8-hydroxy-2-dipropylaminotetralin (0.03-0.56 mg/kg), a full agonist, and buspirone (1.0-10.0 mg/kg), a partial agonist at 5-HT(1A) receptors, partially generalized to the training dose of methamphetamine but only at high doses that decreased response rate. This generalization was antagonized by the coadministration of the 5-HT(1A) antagonist WAY-100635 (1.0 mg/kg). WAY-100635 (1.0 mg/kg) also partially reversed the leftward shift of the methamphetamine dose-response curve produced by fluoxetine. (+/-)-1-(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane (0.3 mg/kg), a 5-HT(2A/2C) agonist, shifted the methamphetamine dose-response curve to the left, and this leftward shift was antagonized by the coadministration of ketanserin (3.0 mg/kg), a 5-HT(2A/2C) antagonist. Ketanserin (3.0 mg/kg) also produced a shift to the right in the methamphetamine dose-response curve and completely reversed the leftward shift in the methamphetamine dose-response curve produced by fluoxetine. In contrast, tropisetron (1.0 mg/kg), a 5-HT(3) antagonist, produced a shift to the left of the methamphetamine dose-response curve, and this effect of tropisetron was antagonized by the coadministration of m-chlorophenyl-biguanide (1.8 mg/kg), a 5-HT(3) agonist. The present data suggest that the 5-HT system plays a modulatory role in the discriminative stimulus effects of methamphetamine. These effects appear to be mediated through 5-HT release and blockade of reuptake and subsequent activation of 5-HT(2A/2C) receptors, with limited involvement of other 5-HT receptor subtypes. JF - The Journal of pharmacology and experimental therapeutics AU - Munzar, P AU - Laufert, M D AU - Kutkat, S W AU - Nováková, J AU - Goldberg, S R AD - Preclinical Pharmacology Laboratory, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 239 EP - 250 VL - 291 IS - 1 SN - 0022-3565, 0022-3565 KW - Biguanides KW - 0 KW - Central Nervous System Stimulants KW - Indoles KW - Piperazines KW - Pyridines KW - Receptors, Serotonin KW - Serotonin Antagonists KW - Serotonin Receptor Agonists KW - Serotonin Uptake Inhibitors KW - Serotonin KW - 333DO1RDJY KW - Methamphetamine KW - 44RAL3456C KW - 1-(3-chlorophenyl)biguanide KW - 48144-44-1 KW - tropisetron KW - 6I819NIK1W KW - N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide KW - 71IH826FEG KW - 8-Hydroxy-2-(di-n-propylamino)tetralin KW - 78950-78-4 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Biguanides -- pharmacology KW - Receptors, Serotonin -- metabolism KW - Piperazines -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - 8-Hydroxy-2-(di-n-propylamino)tetralin -- pharmacology KW - Indoles -- pharmacology KW - Serotonin -- metabolism KW - Pyridines -- pharmacology KW - Male KW - Serotonin Receptor Agonists -- pharmacology KW - Central Nervous System Stimulants -- pharmacology KW - Serotonin Antagonists -- pharmacology KW - Methamphetamine -- pharmacology KW - Serotonin Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70044955?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+various+serotonin+agonists%2C+antagonists%2C+and+uptake+inhibitors+on+the+discriminative+stimulus+effects+of+methamphetamine+in+rats.&rft.au=Munzar%2C+P%3BLaufert%2C+M+D%3BKutkat%2C+S+W%3BNov%C3%A1kov%C3%A1%2C+J%3BGoldberg%2C+S+R&rft.aulast=Munzar&rft.aufirst=P&rft.date=1999-10-01&rft.volume=291&rft.issue=1&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-12 N1 - Date created - 1999-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication of Aleutian mink disease parvovirus in vivo is influenced by residues in the VP2 protein. AN - 70033512; 10482625 AB - Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian disease of mink. Several ADV isolates have been identified which vary in the severity of the disease they elicit. The isolate ADV-Utah replicates to high levels in mink, causing severe Aleutian disease that results in death within 6 to 8 weeks, but does not replicate in Crandell feline kidney (CrFK) cells. In contrast, ADV-G replicates in CrFK cells but does not replicate in mink. The ability of the virus to replicate in vivo is determined by virally encoded determinants contained within a defined region of the VP2 gene (M. E. Bloom, J. M. Fox, B. D. Berry, K. L. Oie, and J. B. Wolfinbarger. Virology 251:288-296, 1998). Within this region, ADV-G and ADV-Utah differ at only five amino acid residues. To determine which of these five amino acid residues comprise the in vivo replication determinant, site-directed mutagenesis was performed to individually convert the amino acid residues of ADV-G to those of ADV-Utah. A virus in which the ADV-G VP2 residue at 534, histidine (H), was converted to an aspartic acid (D) of ADV-Utah replicated in CrFK cells as efficiently as ADV-G. H534D also replicated in mink, causing transient viremia at 30 days postinfection and a strong antibody response. Animals infected with this virus developed diffuse hepatocellular microvesicular steatosis, an abnormal accumulation of intracellular fat, but did not develop classical Aleutian disease. Thus, the substitution of an aspartic acid at residue 534 for a histidine allowed replication of ADV-G in mink, but the ability to replicate was not sufficient to cause classical Aleutian disease. JF - Journal of virology AU - Fox, J M AU - McCrackin Stevenson, M A AU - Bloom, M E AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 8713 EP - 8719 VL - 73 IS - 10 SN - 0022-538X, 0022-538X KW - Capsid Proteins KW - 0 KW - VP2 protein, Aleutian mink disease virus KW - Index Medicus KW - Liver -- virology KW - Animals KW - Liver -- pathology KW - Base Sequence KW - Mink KW - Sequence Analysis KW - Cats KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Virus Replication KW - Aleutian Mink Disease Virus -- physiology KW - Aleutian Mink Disease -- virology KW - Capsid -- physiology KW - Aleutian Mink Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70033512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Replication+of+Aleutian+mink+disease+parvovirus+in+vivo+is+influenced+by+residues+in+the+VP2+protein.&rft.au=Fox%2C+J+M%3BMcCrackin+Stevenson%2C+M+A%3BBloom%2C+M+E&rft.aulast=Fox&rft.aufirst=J&rft.date=1999-10-01&rft.volume=73&rft.issue=10&rft.spage=8713&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-12 N1 - Date created - 1999-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Infect Immun. 1977 Jan;15(1):204-11 [188765] Virology. 1998 Nov 25;251(2):288-96 [9837793] Res Vet Sci. 1978 Mar;24(2):200-4 [206934] J Virol. 1980 Sep;35(3):836-43 [6252342] Lab Invest. 1983 Feb;48(2):140-7 [6296539] Infect Immun. 1983 Sep;41(3):1016-23 [6193063] Gene. 1985;35(1-2):179-85 [3896934] Virology. 1986 Jan 15;148(1):121-32 [3942033] J Virol. 1999 Aug;73(8):6882-91 [10400786] Am J Vet Res. 1958 Jan;19(70):212-22 [13498266] J Virol. 1987 Jan;61(1):81-6 [3023709] Lab Invest. 1987 Jan;56(1):32-6 [3795869] J Virol. 1988 May;62(5):1495-507 [2833604] J Virol. 1990 Jul;64(7):3551-6 [2161958] J Virol. 1990 Dec;64(12):6166-75 [2147041] J Virol. 1991 Feb;65(2):952-6 [1846208] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4358-62 [1852004] Microb Pathog. 1990 Oct;9(4):243-53 [1965846] Int J Exp Pathol. 1991 Oct;72(5):489-500 [1660299] J Infect Dis. 1968 Dec;118(5):510-26 [4178323] J Immunol. 1975 Oct;115(4):1034-7 [51871] Virology. 1992 Apr;187(2):515-24 [1532105] J Virol. 1992 May;66(5):3118-24 [1373202] J Virol. 1992 Sep;66(9):5305-12 [1323697] J Virol. 1992 Sep;66(9):5399-408 [1323703] J Virol. 1992 Dec;66(12):6858-67 [1331498] J Virol. 1993 Apr;67(4):2075-82 [8383229] J Virol. 1993 Oct;67(10):5976-88 [8396664] J Virol. 1994 Feb;68(2):738-49 [8289377] Vet Pathol. 1994 Mar;31(2):216-28 [8203085] Vet Pathol. 1994 Mar;31(2):290-1 [8203105] Infect Agents Dis. 1994 Dec;3(6):279-301 [7889316] J Infect Dis. 1995 Nov;172(5):1198-205 [7594654] Hepatology. 1995 Dec;22(6):1661-5 [7489971] J Virol. 1996 Feb;70(2):852-61 [8551624] Virology. 1996 Jan 15;215(2):186-9 [8560765] Lancet. 1996 Mar 30;347(9005):868-9 [8622394] Lancet. 1996 Jun 1;347(9014):1563-4 [8684141] J Virol. 1996 Jul;70(7):4210-9 [8676441] Virology. 1996 Nov 1;225(1):65-71 [8918534] J Virol. 1997 Jan;71(1):705-14 [8985402] Arch Virol. 1997;142(2):363-73 [9125049] J Virol. 1997 Dec;71(12):9214-22 [9371580] Am J Gastroenterol. 1998 Mar;93(3):468-70 [9517662] Virus Res. 1998 Jul;56(1):41-51 [9784064] Am J Vet Res. 1977 Oct;38(10):1619-24 [201189] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the block in replication of nucleocapsid protein zinc finger mutants from moloney murine leukemia virus. AN - 70029214; 10482569 AB - Mutagenesis studies have shown that retroviral nucleocapsid (NC) protein Zn(2+) fingers (-Cys-X(2)-Cys-X(4)-His-X(4)-Cys- [CCHC]) perform multiple functions in the virus life cycle. Moloney murine leukemia virus mutants His 34-->Cys (CCCC) and Cys 39-->His (CCHH) were able to package their genomes normally but were replication defective. Thermal dissociation experiments showed that the CCHH mutant was not defective in genomic RNA dimer structure. Primer tRNA placement on the viral genome and the ability of the tRNA to function in reverse transcription initiation in vitro also appear normal. Some "full-length" DNA copies of the viral genome were synthesized in mutant virus-infected cells. The CCCC and CCHH mutants produced these DNA copies at greatly reduced levels. Circle junction fragments, amplified from two-long-terminal-repeat viral DNA (vDNA) by PCR, were cloned and characterized. Remarkably, it was discovered that vDNA isolated from cells infected with mutant virions had a wide variety of abnormalities at the site at which the two ends of the linear precursor had been ligated to form the circle (i.e., the junction between the 5' end of U3 and the 3' end of U5). In some molecules, bases were missing from regions corresponding to the U3 and U5 linear vDNA termini; in others, the viral sequences extended either beyond the U5 sequences into the primer-binding site and 5' leader or beyond the U3 sequences into the polypurine tract into the env coding region. Still other molecules contained nonviral sequences between the linear vDNA termini. Such defective genomes would certainly be unsuitable substrates for integration. Thus, strict conservation of the CCHC structure in NC is required for infection events prior to and possibly including integration. JF - Journal of virology AU - Gorelick, R J AU - Fu, W AU - Gagliardi, T D AU - Bosche, W J AU - Rein, A AU - Henderson, L E AU - Arthur, L O AD - AIDS Vaccine Program, SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. gorelick@avpaxp1.ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 8185 EP - 8195 VL - 73 IS - 10 SN - 0022-538X, 0022-538X KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - Zinc Fingers KW - Mice KW - Retroviridae Infections -- virology KW - Leukemia Virus, Murine -- physiology KW - Virus Replication -- genetics KW - Tumor Virus Infections -- virology KW - Capsid -- genetics KW - Point Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70029214?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Characterization+of+the+block+in+replication+of+nucleocapsid+protein+zinc+finger+mutants+from+moloney+murine+leukemia+virus.&rft.au=Gorelick%2C+R+J%3BFu%2C+W%3BGagliardi%2C+T+D%3BBosche%2C+W+J%3BRein%2C+A%3BHenderson%2C+L+E%3BArthur%2C+L+O&rft.aulast=Gorelick&rft.aufirst=R&rft.date=1999-10-01&rft.volume=73&rft.issue=10&rft.spage=8185&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-12 N1 - Date created - 1999-10-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1992 Oct;66(10):6107-16 [1326661] Proc Natl Acad Sci U S A. 1981 Jan;78(1):124-8 [6264426] EMBO J. 1994 Feb 15;13(4):973-81 [7509280] J Virol. 1994 Aug;68(8):5013-8 [8035501] J Virol. 1995 May;69(5):2729-36 [7535863] J Virol. 1995 Oct;69(10):6228-38 [7545245] J Mol Biol. 1995 Oct 6;252(5):563-71 [7563074] J Mol Biol. 1995 Dec 8;254(4):523-37 [7500330] J Virol. 1996 Apr;70(4):2593-7 [8642691] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7577-81 [8755517] Curr Top Microbiol Immunol. 1996;214:177-218 [8791728] J Virol. 1996 Oct;70(10):7132-42 [8794360] J Biol Chem. 1996 Dec 27;271(52):33686-92 [8969239] J Virol. 1997 Jan;71(1):726-8 [8985405] J Virol. 1997 Jun;71(6):4378-84 [9151827] J Virol. 1997 Jul;71(7):5178-88 [9188585] J Virol. 1997 Sep;71(9):6940-6 [9261422] J Virol. 1998 May;72(5):3907-15 [9557676] J Virol. 1998 May;72(5):4442-7 [9557738] J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] J Virol. 1978 Jan;25(1):104-4 [202729] Virology. 1982 Jul 15;120(1):251-7 [6285602] J Virol. 1985 Mar;53(3):899-907 [3882995] Nucleic Acids Res. 1986 Jan 24;14(2):623-33 [2418414] Science. 1986 Apr 25;232(4749):485-7 [2421409] Proc Natl Acad Sci U S A. 1988 Nov;85(22):8420-4 [3141927] Proc Natl Acad Sci U S A. 1989 Jun;86(11):4047-51 [2786206] Cell. 1989 Jul 14;58(1):47-54 [2546673] J Virol. 1990 May;64(5):2421-5 [2157898] J Virol. 1990 Oct;64(10):5076-92 [1697912] Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1339-43 [1847518] J Virol. 1992 Oct;66(10):5735-43 [1382140] Trends Biochem Sci. 1998 Aug;23(8):297-301 [9757830] J Virol. 1999 May;73(5):4251-6 [10196321] J Virol. 1993 Sep;67(9):5443-9 [8350405] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - neu mutation in schwannomas induced transplacentally in Syrian golden hamsters by N-nitrosoethylurea: high incidence but low allelic representation. AN - 70028008; 10473865 AB - Peripheral nerve tumors (PNT) and melanomas induced transplacentally on day 14 of gestation in Syrian golden hamsters by N-nitrosoethylurea were analyzed for activated oncogenes by the NIH 3T3 transfection assay, and for mutations in the neu oncogene by direct sequencing, allele-specific oligonucleotide hybridization, MnlI restriction-fragment-length polymorphism, single-strand conformation polymorphism, and mismatch amplification mutation assays. All (67/67) of the PNT, but none of the melanomas, contained a somatic missense T --> A transversion within the neu oncogene transmembrane domain at a site corresponding to that which also occurs in rat schwannomas transplacentally induced by N-nitrosoethylurea. In only 2 of the 67 individual hamster PNT did the majority of tumor cells appear to carry the mutant neu allele, in contrast to comparable rat schwannomas in which it overwhelmingly predominates. The low fraction of hamster tumor cells carrying the mutation was stable through multiple transplantation passages. In the hamster, as in the rat, specific point-mutational activation of the neu oncogene thus constitutes the major pathway for induction of PNT by transplacental exposure to an alkylating agent, but the low allelic representation of mutant neu in hamster PNT suggests a significant difference in mechanism by which the mutant oncogene acts in this species. JF - Journal of cancer research and clinical oncology AU - Buzard, G S AU - Enomoto, T AU - Hongyo, T AU - Perantoni, A O AU - Diwan, B A AU - Devor, D E AU - Reed, C D AU - Dove, L F AU - Rice, J M AD - Carcinogenesis Study Section, Intramural Research Support Program, SAIC Frederick, Bldg 538, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA. buzardg@mail.ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 529 EP - 540 VL - 125 IS - 10 SN - 0171-5216, 0171-5216 KW - Alkylating Agents KW - 0 KW - DNA, Neoplasm KW - Mutagens KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Receptor, ErbB-2 -- genetics KW - Polymerase Chain Reaction KW - Animals KW - Transfection KW - Polymorphism, Restriction Fragment Length KW - Blotting, Southern KW - Placenta KW - Mesocricetus KW - Incidence KW - DNA, Neoplasm -- analysis KW - Cricetinae KW - Fetal Diseases -- genetics KW - Neurilemmoma -- chemically induced KW - Peripheral Nervous System Neoplasms -- chemically induced KW - Melanoma -- chemically induced KW - Peripheral Nervous System Neoplasms -- genetics KW - Genes, erbB-2 -- genetics KW - Ethylnitrosourea -- adverse effects KW - Neurilemmoma -- genetics KW - Genes, erbB-2 -- drug effects KW - Alleles KW - Melanoma -- genetics KW - Mutagens -- adverse effects KW - Alkylating Agents -- adverse effects KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70028008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cancer+research+and+clinical+oncology&rft.atitle=neu+mutation+in+schwannomas+induced+transplacentally+in+Syrian+golden+hamsters+by+N-nitrosoethylurea%3A+high+incidence+but+low+allelic+representation.&rft.au=Buzard%2C+G+S%3BEnomoto%2C+T%3BHongyo%2C+T%3BPerantoni%2C+A+O%3BDiwan%2C+B+A%3BDevor%2C+D+E%3BReed%2C+C+D%3BDove%2C+L+F%3BRice%2C+J+M&rft.aulast=Buzard&rft.aufirst=G&rft.date=1999-10-01&rft.volume=125&rft.issue=10&rft.spage=529&rft.isbn=&rft.btitle=&rft.title=Journal+of+cancer+research+and+clinical+oncology&rft.issn=01715216&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-28 N1 - Date created - 1999-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of P-glycoprotein activity and reversal of multidrug resistance in vitro by rosemary extract. AN - 69432736; 10673984 AB - The transmembrane transport pump P-glycoprotein (Pgp) causes the efflux of chemotherapeutic agents from cells and is believed to be an important mechanism in multidrug resistance (MDR) in mammary tumours. In the present study we demonstrate that an extract of the common dietary herb rosemary (Rosemarinus officinalis Labiatae), increases the intracellular accumulation of commonly used chemotherapeutic agents, including doxorubicin (DOX) and vinblastine (VIN), in drug-resistant MCF-7 human breast cancer cells which express Pgp. Rosemary extract (RE) inhibits the efflux of DOX and VIN, which are known to be substrates of Pgp, but does not affect accumulation or efflux of DOX in wild type MCF-7 cells, which lack Pgp. Treatment of drug-resistant cells with RE increases their sensitivity to DOX, which is consistent with an increased intracellular accumulation of the drug. RE blocks the binding of the VIN analogue azidopine to Pgp. Thus, it appears that RE directly inhibits Pgp activity by inhibiting the binding of drugs to Pgp. JF - European journal of cancer (Oxford, England : 1990) AU - Plouzek, C A AU - Ciolino, H P AU - Clarke, R AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Maryland 21701, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 1541 EP - 1545 VL - 35 IS - 10 SN - 0959-8049, 0959-8049 KW - Antineoplastic Agents KW - 0 KW - P-Glycoproteins KW - Plant Extracts KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Plant Extracts -- pharmacology KW - Drug Screening Assays, Antitumor KW - Humans KW - Drug Resistance, Neoplasm KW - Drug Resistance, Multiple KW - Breast Neoplasms -- drug therapy KW - Lamiaceae -- chemistry KW - Breast Neoplasms -- metabolism KW - Doxorubicin -- therapeutic use KW - P-Glycoproteins -- antagonists & inhibitors KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69432736?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.atitle=Inhibition+of+P-glycoprotein+activity+and+reversal+of+multidrug+resistance+in+vitro+by+rosemary+extract.&rft.au=Plouzek%2C+C+A%3BCiolino%2C+H+P%3BClarke%2C+R%3BYeh%2C+G+C&rft.aulast=Plouzek&rft.aufirst=C&rft.date=1999-10-01&rft.volume=35&rft.issue=10&rft.spage=1541&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+%28Oxford%2C+England+%3A+1990%29&rft.issn=09598049&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-03-02 N1 - Date created - 2000-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tamoxifen and fenretinide in women with metastatic breast cancer. AN - 69382320; 10617304 AB - Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies. JF - Breast cancer research and treatment AU - Zujewski, J AU - Pai, L AU - Wakefield, L AU - Giusti, R AU - Dorr, F A AU - Flanders, C AU - Caruso, R AU - Kaiser, M AU - Goodman, L AU - Merino, M AU - Gossard, M AU - Noone, M A AU - Denicoff, A AU - Venzon, D AU - Cowan, K H AU - O'Shaughnessy, J A AD - Medicine Branch, National Cancer Institute, Bethesda 20892, MD, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 277 EP - 283 VL - 57 IS - 3 SN - 0167-6806, 0167-6806 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Lipids KW - Transforming Growth Factor beta KW - Tamoxifen KW - 094ZI81Y45 KW - Fenretinide KW - 187EJ7QEXL KW - Index Medicus KW - Lipids -- blood KW - Humans KW - Disease Progression KW - Aged KW - Fenretinide -- administration & dosage KW - Pilot Projects KW - Tamoxifen -- administration & dosage KW - Transforming Growth Factor beta -- analysis KW - Adult KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Treatment Outcome KW - Middle Aged KW - Female KW - Breast Neoplasms -- drug therapy KW - Breast Neoplasms -- pathology KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69382320?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Breast+cancer+research+and+treatment&rft.atitle=Tamoxifen+and+fenretinide+in+women+with+metastatic+breast+cancer.&rft.au=Zujewski%2C+J%3BPai%2C+L%3BWakefield%2C+L%3BGiusti%2C+R%3BDorr%2C+F+A%3BFlanders%2C+C%3BCaruso%2C+R%3BKaiser%2C+M%3BGoodman%2C+L%3BMerino%2C+M%3BGossard%2C+M%3BNoone%2C+M+A%3BDenicoff%2C+A%3BVenzon%2C+D%3BCowan%2C+K+H%3BO%27Shaughnessy%2C+J+A&rft.aulast=Zujewski&rft.aufirst=J&rft.date=1999-10-01&rft.volume=57&rft.issue=3&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Breast+cancer+research+and+treatment&rft.issn=01676806&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-18 N1 - Date created - 2000-01-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Capillary electrophoresis of natural products-II. AN - 69349200; 10596825 AB - Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) were used for the separation of widely different compounds from natural materials including compounds from tea, acids from different matrices, flavonoids and alkaloids, toxins and toxicological compounds, proteins and polypeptides, biogenic amines, phenolic compounds in alcoholic beverages, Chinese medicinal drugs, compounds in cells and cell extracts, and miscellaneous other applications. A section dealing with recent reviews related to natural products is also included. JF - Electrophoresis AU - Issaq, H J AD - SAIC Frederick, NCI-Frederick Cancer Research and Development Center, MD 21702, USA. issaqh@mail.ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 3190 EP - 3202 VL - 20 IS - 15-16 SN - 0173-0835, 0173-0835 KW - Alkaloids KW - 0 KW - Biogenic Amines KW - Biological Products KW - Flavonoids KW - Peptides KW - Proteins KW - Tea KW - Toxins, Biological KW - Index Medicus KW - Flavonoids -- analysis KW - Humans KW - Medicine, Chinese Traditional KW - Peptides -- analysis KW - Tea -- chemistry KW - Proteins -- analysis KW - Toxins, Biological -- analysis KW - Biogenic Amines -- analysis KW - Alkaloids -- analysis KW - Biological Products -- analysis KW - Electrophoresis, Capillary -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69349200?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Capillary+electrophoresis+of+natural+products-II.&rft.au=Issaq%2C+H+J&rft.aulast=Issaq&rft.aufirst=H&rft.date=1999-10-01&rft.volume=20&rft.issue=15-16&rft.spage=3190&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-21 N1 - Date created - 1999-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isolated organ perfusion does not result in systemic microembolization of tumor cells. AN - 69271031; 10560851 AB - Isolated organ perfusion with hyperthermia and melphalan with or without tumor necrosis factor-alpha has been effectively used to treat regionally confined, unresectable malignancies of both the limb and liver. Many patients, however, will eventually relapse at distant sites. We used reverse transcription-polymerase chain reaction (RT-PCR) to determine whether significant tumor microembolization occurs in patients undergoing isolated limb perfusion (ILP), isolated hepatic perfusion (IHP), or hepatic resection. Primers specific for the human tyrosinase gene or carcinoembryonic antigen gene were designed for RT-PCR to screen melanoma or colon adenocarcinoma, respectively. RNA from human melanoma lines (Pmel and 1286) and human colon adenocarcinoma lines (H508 and HT29) were used to generate positive control cDNA. Normal human blood was inoculated with tumor cells at concentrations that ranged from 10(-2) to 10(5) tumor cells/ml of blood to define the sensitivity. Systemic and perfusate blood samples were drawn from 15 patients (8 patients underwent IHP, 5 patients underwent ILP, and 2 patients underwent resection) before the start of the operation, immediately before and during the perfusion, and postoperatively. Mononuclear cell fractions were separated from the blood samples and RNA was extracted for the RT-PCR assay. Standard primers for human beta-actin were used to confirm that cDNA was generated after the RT reaction. RT-PCR assay sensitivity was determined to be 10 tumor cells/ml of whole blood. Of the 8 IHP patients, 6 had colon metastases and 2 had ocular melanoma metastases to the liver. All 5 ILP patients had in transit melanoma of the extremity. Two patients with colon metastases to the liver were found to have resectable disease. There were no detectable circulating tumor cells in the systemic circulation either preoperatively or postoperatively in all 15 patients that were screened. RT-PCR is a highly sensitive method of detecting tumor cells in perfusate or blood. Manipulation of the limb or liver followed by resection or isolated hyperthermic perfusion does not cause detectable release of circulating tumor cells. The late development of distant metastases observed in many of these patients does not correlate with the ability to measure circulating tumor cells during regional therapy. JF - Annals of surgical oncology AU - Wu, P C AU - McCart, A AU - Hewitt, S M AU - Turner, E AU - Libutti, S K AU - Bartlett, D L AU - Alexander, H R AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1999 SP - 658 EP - 663 VL - 6 IS - 7 SN - 1068-9265, 1068-9265 KW - Antineoplastic Agents, Alkylating KW - 0 KW - DNA, Neoplasm KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Extremities KW - Melanoma -- pathology KW - Melphalan -- administration & dosage KW - Humans KW - Hyperthermia, Induced KW - Molecular Sequence Data KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Amino Acid Sequence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Neoplastic Cells, Circulating -- pathology KW - Liver Neoplasms -- drug therapy KW - Adenocarcinoma -- secondary KW - DNA, Neoplasm -- analysis KW - Chemotherapy, Cancer, Regional Perfusion -- adverse effects KW - Liver Neoplasms -- secondary KW - Colonic Neoplasms -- pathology KW - Adenocarcinoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69271031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Isolated+organ+perfusion+does+not+result+in+systemic+microembolization+of+tumor+cells.&rft.au=Wu%2C+P+C%3BMcCart%2C+A%3BHewitt%2C+S+M%3BTurner%2C+E%3BLibutti%2C+S+K%3BBartlett%2C+D+L%3BAlexander%2C+H+R&rft.aulast=Wu&rft.aufirst=P&rft.date=1999-10-01&rft.volume=6&rft.issue=7&rft.spage=658&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-03 N1 - Date created - 1999-12-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Surg Oncol. 1999 Oct-Nov;6(7):631-2 [10560846] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Principles of chemoradiation: theoretical and practical considerations. AN - 69235373; 10550823 AB - Chemotherapy agents known to enhance the effects of radiation in preclinical studies have been used concurrently with radiotherapy in numerous clinical trials with the prospect of further enhancing radiation-induced local tumor control. While some success in several tumor histologies has been achieved using this approach, a major concern has been enhancement in normal tissue toxicity. This brief review addresses both theoretical and practical issues with respect to chemoradiation clinical trials. Recommendations for clinical trials are provided that, if implemented, can increase our understanding of basic mechanisms (in patients) and provide a more rational approach for future trials. JF - Oncology (Williston Park, N.Y.) AU - Herscher, L L AU - Cook, J A AU - Pacelli, R AU - Pass, H I AU - Russo, A AU - Mitchell, J B AD - Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 11 EP - 22 VL - 13 IS - 10 Suppl 5 SN - 0890-9091, 0890-9091 KW - Antineoplastic Agents KW - 0 KW - Radiation-Protective Agents KW - Radiation-Sensitizing Agents KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Animals KW - Combined Modality Therapy KW - Humans KW - Paclitaxel -- pharmacology KW - Drug Resistance, Neoplasm KW - Chemotaxis, Leukocyte KW - Clinical Trials as Topic -- methods KW - DNA Repair -- drug effects KW - DNA Damage -- drug effects KW - DNA Repair -- radiation effects KW - Clinical Trials as Topic -- trends KW - DNA Damage -- radiation effects KW - Cell Cycle -- radiation effects KW - Cell Cycle -- drug effects KW - Neoplasms -- drug therapy KW - Neoplasms -- radiotherapy KW - Dose-Response Relationship, Drug KW - Radiation-Sensitizing Agents -- pharmacology KW - Radiation-Protective Agents -- pharmacology KW - Dose-Response Relationship, Radiation KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69235373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology+%28Williston+Park%2C+N.Y.%29&rft.atitle=Principles+of+chemoradiation%3A+theoretical+and+practical+considerations.&rft.au=Herscher%2C+L+L%3BCook%2C+J+A%3BPacelli%2C+R%3BPass%2C+H+I%3BRusso%2C+A%3BMitchell%2C+J+B&rft.aulast=Herscher&rft.aufirst=L&rft.date=1999-10-01&rft.volume=13&rft.issue=10+Suppl+5&rft.spage=11&rft.isbn=&rft.btitle=&rft.title=Oncology+%28Williston+Park%2C+N.Y.%29&rft.issn=08909091&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-23 N1 - Date created - 1999-11-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lack of p53-mediated G1 arrest in response to an environmental carcinogen. AN - 69232975; 10545796 AB - The environmental carcinogen, 5-methylchrysene, is a component of cigarette smoke. Its reactive metabolite, anti-5-methylchrysene-1, 2-dihydrodiol-3,4-epoxide (5-MeCDE) mainly reacts with the N(2)-position of guanine residues in the DNA molecule. In this study, we demonstrate that the tumor suppressor protein p53 is stabilized in response to DNA damage by 5-MeCDE but fails to induce the cells' protective mechanism of G1 arrest in the human breast carcinoma cell line, MCF-7. In contrast, actinomycin D treatment of these cells did lead to G1 arrest. Western analyses revealed that, though both actinomycin D and 5-MeCDE treatment stabilized p53, only trace levels of p21(waf1/cip1) were seen in the latter case. This lack of p21(waf1/cip1) expression in 5-MeCDE-treated cells is attributed to a stealth characteristic of this environmental carcinogen that allows it to damage DNA and still escape the p53-mediated cellular defense mechanism of G1 arrest. JF - Oncology AU - Khan, Q A AU - Vousden, K H AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Md., USA. Khanq@ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - October 1999 SP - 258 EP - 264 VL - 57 IS - 3 SN - 0030-2414, 0030-2414 KW - Carcinogens KW - 0 KW - Chrysenes KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - 1,2-dihydroxy-epoxy-1,2,3,4-tetrahydro-5-methylchrysene KW - 81851-68-5 KW - 5-methylchrysene KW - O66195MC8L KW - Index Medicus KW - DNA, Neoplasm -- drug effects KW - Blotting, Western KW - Tumor Cells, Cultured KW - Humans KW - Smoking -- adverse effects KW - Flow Cytometry KW - Breast Neoplasms -- genetics KW - DNA Damage KW - Breast Neoplasms -- metabolism KW - G1 Phase -- drug effects KW - Breast Neoplasms -- chemically induced KW - Tumor Suppressor Protein p53 -- metabolism KW - Chrysenes -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69232975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncology&rft.atitle=Lack+of+p53-mediated+G1+arrest+in+response+to+an+environmental+carcinogen.&rft.au=Khan%2C+Q+A%3BVousden%2C+K+H%3BDipple%2C+A&rft.aulast=Khan&rft.aufirst=Q&rft.date=1999-10-01&rft.volume=57&rft.issue=3&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Oncology&rft.issn=00302414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-30 N1 - Date created - 1999-11-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of human mu opioid receptor extracellular "disulfide cysteine" residues alters ligand binding but does not prevent receptor targeting to the cell plasma membrane. AN - 69207984; 10529478 AB - The mu opioid receptor, a primary site of action in the brain for opioid neuropeptides and opiate drugs of abuse, is a member of the seven transmembrane, G protein-coupled receptor (GPCR) superfamily. Two cysteine residues, one in each of the first two of three extracellular loops (ECLs), are highly conserved among GPCRs, and there is direct or circumstantial evidence that the residues form a disulfide bond in many of these receptors. Such a bond would dramatically govern the topology of the ECLs, and possibly affect the position of the membrane-spanning domains. Recent findings from several laboratories indicate the importance of the ECLs for opioid ligand selectivity. These conserved cysteine residues in the mu opioid receptor were studied using site-directed mutagenesis. Little or no specific binding of radiolabled opiate alkaloid or opioid peptide agonists or antagonists was observed for receptors mutated at either "disulfide cysteine" residue. Each mutant mu opioid receptor was expressed in both transiently- and stably-transfected cells, in some cases at levels comparable to the wild type receptor. The two point mutants possessing serine-for-cysteine substitutions were also observed to successfully reach the cell plasma membrane, as evidenced by electron microscopy. Consistent with related work with other GPCRs, the mu opioid receptor apparently also employs the extracellular disulfide bond. This information now permits accurate molecular modeling of extracellular aspects of the receptor, including plausible scenarios of mu receptor docking of opioid ligands known to require specific extracellular loop features for high affinity binding. JF - Brain research. Molecular brain research AU - Zhang, P AU - Johnson, P S AU - Zöllner, C AU - Wang, W AU - Wang, Z AU - Montes, A E AU - Seidleck, B K AU - Blaschak, C J AU - Surratt, C K AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 195 EP - 204 VL - 72 IS - 2 SN - 0169-328X, 0169-328X KW - Ligands KW - 0 KW - Narcotic Antagonists KW - Nerve Tissue Proteins KW - Peptides KW - Receptors, Opioid, mu KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- KW - 100929-53-1 KW - Naloxone KW - 36B82AMQ7N KW - Cystine KW - 48TCX9A1VT KW - connective tissue-activating peptide KW - 69344-77-0 KW - Morphine KW - 76I7G6D29C KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Naloxone -- metabolism KW - COS Cells KW - Cricetulus KW - Humans KW - Enkephalin, Ala(2)-MePhe(4)-Gly(5)- -- metabolism KW - Peptides -- metabolism KW - Radioligand Assay KW - Morphine -- metabolism KW - Protein Binding KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Cystine -- chemistry KW - Transfection KW - Cercopithecus aethiops KW - Point Mutation KW - CHO Cells KW - Narcotic Antagonists -- metabolism KW - Protein Structure, Tertiary KW - Amino Acid Substitution KW - Cricetinae KW - Cysteine -- chemistry KW - Nerve Tissue Proteins -- metabolism KW - Receptors, Opioid, mu -- chemistry KW - Receptors, Opioid, mu -- metabolism KW - Nerve Tissue Proteins -- genetics KW - Nerve Tissue Proteins -- chemistry KW - Receptors, Opioid, mu -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69207984?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Mutation+of+human+mu+opioid+receptor+extracellular+%22disulfide+cysteine%22+residues+alters+ligand+binding+but+does+not+prevent+receptor+targeting+to+the+cell+plasma+membrane.&rft.au=Zhang%2C+P%3BJohnson%2C+P+S%3BZ%C3%B6llner%2C+C%3BWang%2C+W%3BWang%2C+Z%3BMontes%2C+A+E%3BSeidleck%2C+B+K%3BBlaschak%2C+C+J%3BSurratt%2C+C+K&rft.aulast=Zhang&rft.aufirst=P&rft.date=1999-10-01&rft.volume=72&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-06 N1 - Date created - 1999-12-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effect of doxycycline treatment on the development of protective immunity in a murine model of chlamydial genital infection AN - 18306571; 5352539 AB - Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) worldwide. Antibiotics are effective in treating infection; however, reinfection is common. This observation has led to the conclusion that infection fails to elicit a protective antichlamydial immune response. It was postulated that high reinfection rates might be due to early eradication of organisms from genital tissue after antibiotic intervention, which could negatively influence the development of naturally acquired protective immunity. This hypothesis was tested by use of a murine model of female genital infection. The findings show that doxycycline intervention of infection, although very effective in eradicating chlamydiae from genital tissue and preventing upper genital tract disease, significantly inhibits the development of protective immunity. If antibiotic intervention of human chlamydial genital infection has a similar effect on protective immunity, it could have important implications in the understanding of immunity to infection and future public health efforts to control chlamydial STD. JF - Journal of Infectious Diseases AU - Su, H AU - Morrison, R AU - Messer, R AU - Whitmire, W AU - Hughes, S AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, Hamilton, Montana, USA Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 1252 EP - 1258 VL - 180 IS - 4 SN - 0022-1899, 0022-1899 KW - Microbiology Abstracts B: Bacteriology KW - Sexually-transmitted diseases KW - Animal models KW - Chlamydia trachomatis KW - Genital tract KW - Immune response KW - Doxycycline KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18306571?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Infectious+Diseases&rft.atitle=The+effect+of+doxycycline+treatment+on+the+development+of+protective+immunity+in+a+murine+model+of+chlamydial+genital+infection&rft.au=Su%2C+H%3BMorrison%2C+R%3BMesser%2C+R%3BWhitmire%2C+W%3BHughes%2C+S%3BCaldwell%2C+H+D&rft.aulast=Su&rft.aufirst=H&rft.date=1999-10-01&rft.volume=180&rft.issue=4&rft.spage=1252&rft.isbn=&rft.btitle=&rft.title=Journal+of+Infectious+Diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Sexually-transmitted diseases; Genital tract; Doxycycline; Immune response; Animal models ER - TY - JOUR T1 - Breast cancer risk in young women and history of selected medical conditions AN - 18160073; 4660197 AB - Background. Several common medical conditions are associated with altered hormone levels, and may thus plausibly influence breast cancer risk. Few studies have examined such relationships, and we utilized a population-based case-control study of young women in the US to examine breast cancer risk following a history of various medical conditions. Relationships between breast cancer and each medical condition examined are biologically plausible, and relevant in terms of public health. Method. The study included 2173 breast cancer cases and 1990 population-based controls from three areas of the US, under 55 years, who were administered a questionnaire including details of physician-diagnosed medical conditions. Results. No significantly increased or decreased breast cancer risk was associated with a history of thyroid disease, gallbladder disease, colorectal polyps, diabetes, high blood pressure, high cholesterol or surgery for endometriosis. There was some evidence of an increased breast cancer risk associated with ovarian cysts among women who did not receive an oophorectomy (relative risk [RR] = 1.94, 95% CI:1.0-3.9). Non-significant increases in breast cancer risk were observed following diagnoses of several other cancers, including thyroid cancer, basal cell carcinoma, Hodgkin's disease and malignant melanoma. Conclusion. To conclude, our generally null results from this large, population-based study support results from previous studies in providing reassurance that women with a history of several common medical conditions do not appear to be at an increased risk of breast cancer at a young age. JF - International Journal of Epidemiology AU - Weiss, HA AU - Brinton, LA AU - Potischman, NA AU - Brogan, D AU - Coates, R J AU - Gammon, MD AU - Malone, KE AU - Schoenberg, J B AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South Rm 7068, 6120 Exec. Blvd. MSC 7234 Bethesda, MD 20892-7234, USA Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 816 EP - 823 VL - 28 IS - 5 SN - 0300-5771, 0300-5771 KW - blood pressure KW - diabetes mellitus KW - endometriosis KW - probability KW - Risk Abstracts KW - Breast cancer KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18160073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Epidemiology&rft.atitle=Breast+cancer+risk+in+young+women+and+history+of+selected+medical+conditions&rft.au=Weiss%2C+HA%3BBrinton%2C+LA%3BPotischman%2C+NA%3BBrogan%2C+D%3BCoates%2C+R+J%3BGammon%2C+MD%3BMalone%2C+KE%3BSchoenberg%2C+J+B&rft.aulast=Weiss&rft.aufirst=HA&rft.date=1999-10-01&rft.volume=28&rft.issue=5&rft.spage=816&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Epidemiology&rft.issn=03005771&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast cancer ER - TY - JOUR T1 - Occupational Exposure to Crystalline Silica and Autoimmune Disease AN - 17587112; 4677017 AB - Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures. JF - Environmental Health Perspectives AU - Parks, C G AU - Conrad, K AU - Cooper, G S AD - Epidemiology Branch, National Institute of Environmental Health Sciences, MD A3-05, PO Box 12233, Research Triangle Park, NC 27709, USA, parks@niehs.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 793 EP - 802 VL - 107 SN - 0091-6765, 0091-6765 KW - immunology KW - genetic factors KW - silicon dioxide KW - man KW - autoimmune diseases KW - rheumatoid arthritis KW - silica KW - Risk Abstracts; Toxicology Abstracts; Immunology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Autoimmune diseases KW - Wegener's granulomatosis KW - Environmental factors KW - Dust KW - Quartz KW - Scleroderma KW - Systemic lupus erythematosus KW - Occupational exposure KW - Immunology KW - Rheumatoid arthritis KW - Silica KW - Reviews KW - R2 23080:Industrial and labor KW - F 06874:General KW - X 24164:Pathology KW - H 1000:Occupational Safety and Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17587112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Occupational+Exposure+to+Crystalline+Silica+and+Autoimmune+Disease&rft.au=Parks%2C+C+G%3BConrad%2C+K%3BCooper%2C+G+S&rft.aulast=Parks&rft.aufirst=C&rft.date=1999-10-01&rft.volume=107&rft.issue=&rft.spage=793&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special Issue: Linking Environmental Agents to Autoimmune Diseases. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dust; Occupational exposure; Immunology; Autoimmune diseases; Wegener's granulomatosis; Environmental factors; Reviews; Scleroderma; Rheumatoid arthritis; Systemic lupus erythematosus; Silica; Quartz ER - TY - JOUR T1 - Formation of Deaminated Products in Styrene Oxide Reactions with Deoxycytidine AN - 17503846; 4692258 AB - The reaction of racemic styrene oxide with deoxycytidine under aqueous conditions was studied. The four principal products isolated were a pair of diastereomeric N super(4)-(2-hydroxy-1-phenylethyl)deoxycytidines ( similar to 20% of the products) and a pair of diastereomeric 3-(2-hydroxy-2-phenylethyl)deoxyuridines ( similar to 80% of the products). Reactions with optically active styrene oxides allowed the configurations of the 3-(2-hydroxy-2-phenylethyl)deoxyuridines to be assigned, and these structures were confirmed by an independent synthesis from deoxyuridine. Also, it was possible to tentatively assign the configurations of the N super(4)-(2-hydroxy-1-phenylethyl)deoxycytidines that had undergone some racemization during the reaction (the ratio of the retained to inverted configuration of the products was similar to 1:7). JF - Chemical Research in Toxicology AU - Barlow, T AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, Maryland 21702, USA Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 883 EP - 886 VL - 12 IS - 10 SN - 0893-228X, 0893-228X KW - reaction products KW - deoxycytidine KW - styrene oxide KW - Toxicology Abstracts KW - X 24155:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17503846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Formation+of+Deaminated+Products+in+Styrene+Oxide+Reactions+with+Deoxycytidine&rft.au=Barlow%2C+T%3BDipple%2C+A&rft.aulast=Barlow&rft.aufirst=T&rft.date=1999-10-01&rft.volume=12&rft.issue=10&rft.spage=883&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair AN - 17455324; 4659282 AB - A 10-week inpatient study was performed to evaluate cocaine, codeine, and metabolite disposition in biological matrices collected from volunteers. An initial report described drug disposition in plasma, sebum, and stratum corneum collected from five African-American males. This report focuses on drug disposition in hair and sweat collected from the same five subjects. Following a three-week washout period, three doses of cocaine HCl (75 mg/70 kg, subcutaneous) and three doses of codeine SO sub(4) (60 mg/70 kg, oral) were administered on alternating days in week 4 (low-dose week). The same dosing sequence was repeated in week 8 with doubled doses (high-dose week). Hair was collected by shaving the entire scalp once each week. Hair from the anterior vertex was divided into two portions. One portion was washed with isopropanol and phosphate buffer; the other portion was not washed. Hair was enzymatically digested, samples were centrifuged, and the supernatant was collected. Sweat was collected periodically by placing PharmChek sweat patches on the torso. Drugs were extracted from sweat patches with methanol/0.2M sodium acetate buffer (75:25, v/v). Supernatants from hair digests, hair washes, and sweat patch extracts were processed by solid-phase extraction followed by gas chromatography-mass spectrometry analysis for cocaine, codeine, 6-acetylmorphine, and metabolites. Cocaine and codeine were the primary analytes identified in sweat patches and hair. Drugs were detected in sweat within 8 h after dosing, and drug secretion primarily occurred within 24 h after dosing. No clear relationship was observed between dose and drug concentrations in sweat. Drug incorporation into hair appeared to be dose-dependent. Drugs were detected in hair within 1-3 days after the last drug administration; peak drug concentrations generally occurred in the following 1-2 weeks; thereafter, drug concentrations decreased. Solvent washes removed 50-55% of cocaine and codeine from hair collected 1-3 days after the last drug dose. These data may reflect removal of drug that was deposited by sweat shortly after dosing. Drug removed by washing hair collected 1-3 weeks after the last dose was minimal for cocaine but variable for codeine. Drug in these specimens was likely transferred from blood to germinative hair cells followed by emergence of drug in growing hair. These findings suggest that drug deposition in hair occurs by multiple mechanisms. JF - Journal of Analytical Toxicology AU - Joseph, RE Jr AU - Hoeld, K M AU - Wilkins, D G AU - Rollins, DE AU - Cone, E J AD - Addiction Research Center, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 396 EP - 408 VL - 23 IS - 6 SN - 0146-4760, 0146-4760 KW - man KW - deposition KW - Toxicology Abstracts KW - Drug abuse KW - Cocaine KW - Hair KW - Codeine KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17455324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Drug+testing+with+alternative+matrices+II.+Mechanisms+of+cocaine+and+codeine+deposition+in+hair&rft.au=Joseph%2C+RE+Jr%3BHoeld%2C+K+M%3BWilkins%2C+D+G%3BRollins%2C+DE%3BCone%2C+E+J&rft.aulast=Joseph&rft.aufirst=RE&rft.date=1999-10-01&rft.volume=23&rft.issue=6&rft.spage=396&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Society of Forensic Toxico logists, Inc. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Codeine; Drug abuse; Hair ER - TY - JOUR T1 - Pregnancy recency and risk of ovarian cancer AN - 17448361; 4657692 AB - A recent analysis suggested that ovarian cancer risk increased with time since last birth, possibly because of some aspect of pregnancy that affects the clearance of cells that have undergone malignant transformation. We analyzed data from four case-control studies pertaining to ovarian cancer risk in relation to age at first pregnancy, age at last pregnancy, and years since last pregnancy: 628 cases and 3432 neighborhood or population controls, ages 18-79, were included. We used logistic regression to analyze associations between ovarian cancer risk, controlling for study, age (at diagnosis or corresponding reference age for controls), race, parity, oral contraceptive use, tubal ligation, family history of ovarian or breast cancer, and excluding women with a history of infertility. An early age at first pregnancy was associated with an increased risk of ovarian cancer (odds ratio 1.4, 95% confidence interval (1.1-1.8) for ages less than or equal to 19 compared to greater than or equal to 25). Years since last pregnancy was also associated with increased ovarian cancer risk, with odds ratios of 1.4, 1.4, 1.8, and 2.1 for 10-14, 15-19, 20-24, and greater than or equal to 25 years compared to 0-9 years (trend test p = 0.004), respectively. These observations support the results from the previous study, and raise additional questions about the role of pregnancy in the etiology of ovarian cancer. JF - Cancer Causes & Control AU - Cooper, G S AU - Schildkraut, J M AU - Whittemore, A S AU - Marchbanks, P A AD - Epidemiology Branch A3-05, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, cooper1@niehs.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 397 EP - 402 VL - 10 IS - 5 SN - 0957-5243, 0957-5243 KW - ovarian carcinoma KW - Risk Abstracts KW - Age KW - Cancer KW - Pregnancy KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17448361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Pregnancy+recency+and+risk+of+ovarian+cancer&rft.au=Cooper%2C+G+S%3BSchildkraut%2C+J+M%3BWhittemore%2C+A+S%3BMarchbanks%2C+P+A&rft.aulast=Cooper&rft.aufirst=G&rft.date=1999-10-01&rft.volume=10&rft.issue=5&rft.spage=397&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1023%2FA%3A1008960520316 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Age; Pregnancy DO - http://dx.doi.org/10.1023/A:1008960520316 ER - TY - JOUR T1 - Growth Inhibition of Cervical Tumor Cells by Antisense Oligodeoxynucleotides Directed to the Human Papillomavirus Type 16 E6 Gene AN - 17445145; 4652564 AB - Human papillomavirus type 16 (HPV-16) is the HPV type most frequently associated with cervical carcinomas. Based on our previous research with anti-HPV ribozymes, we developed a 16-nucleotide antisense oligodeoxynucleotide (AntiE6) able to direct RNase H activity on full-length HPV-16 E6/E7 mRNA. Although the precise mechanism is not completely understood, addition of 50 mu M AntiE6 oligodeoxynucleotide in sterile water caused a significant decrease in the growth rate of CaSki and QGU cervical tumor cell lines. In contrast, addition of a mismatched mutant oligodeoxynucleotide (M7) did not affect cell growth after 72 hours. Treatment with AntiE6 resulted in down-regulation of E6/E7 mRNA and an increase in p53 levels in QGU cells. AntiE6 was also able to (>70%) inhibit significantly growth of transplanted cervical tumors in nude mice after 2 weeks treatment using constant delivery by osmotic pumps. These results indicate that the AntiE6 antisense oligodeoxynucleotides can act as a therapeutic agent against cervical carcinomas. JF - Antisense and Nucleic Acid Drug Development AU - Alvarez-Salas, L M AU - Arpawong, TE AU - Dipaolo, JA AD - Department of Health & Human Services, NCI/NIH, Laboratory of Biology, Building 37, Room 2A19, Bethesda, MD 20892, USA, dipaoloj@dc37a.nci.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 441 EP - 450 VL - 9 IS - 5 SN - 1087-2906, 1087-2906 KW - man KW - nude mice KW - Human papillomavirus 16 KW - double prime E6 gene KW - oligodeoxynucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - E6 gene KW - ^AE6 gene KW - Cervical carcinoma KW - Antisense KW - Cervix KW - Tumor cells KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17445145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Growth+Inhibition+of+Cervical+Tumor+Cells+by+Antisense+Oligodeoxynucleotides+Directed+to+the+Human+Papillomavirus+Type+16+E6+Gene&rft.au=Alvarez-Salas%2C+L+M%3BArpawong%2C+TE%3BDipaolo%2C+JA&rft.aulast=Alvarez-Salas&rft.aufirst=L&rft.date=1999-10-01&rft.volume=9&rft.issue=5&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus 16; Antisense; Tumor cells; Cervix; Cervical carcinoma ER - TY - JOUR T1 - Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma AN - 17419269; 4636506 AB - Lymphomas express a tumor-specific antigen which can be targeted by cancer vaccination. We evaluated the ability of a new idiotype protein vaccine formulation to eradicate residual t(14; 18)+ lymphoma cells in 20 patients in a homogeneous, chemotherapy-induced first clinical complete remission. All 11 patients with detectable translocations in their primary tumors had cells from the malignant clone detectable in their blood by PCR both at diagnosis and after chemotherapy, despite being in complete remission. However, 8 of 11 patients converted to lacking cells in their blood from the malignant clone detectable by PCR after vaccination and sustained their molecular remissions. Tumor-specific cytotoxic CD8 super(+) and CD4 super(+) T cells were uniformly found (19 of 20 patients), whereas antibodies were detected, but apparently were not required for molecular remission. Vaccination was thus associated with clearance of residual tumor cells from blood and long-term disease-free survival. The demonstration of molecular remissions, analysis of cytotoxic T lymphocytes against autologous tumor targets, and addition of granulocyte-monocyte colony-stimulating factor to the vaccine formulation provide principles relevant to the design of future clinical trials of other cancer vaccines administered in a minimal residual disease setting. JF - Nature Medicine AU - Bendandi, M AU - Gocke, C D AU - Kobrin, C B AU - Benko, F A AU - Sternas, LA AU - Pennington, R AU - Watson, T M AU - Reynolds, C W AU - Gause, B L AU - Duffey, P L AU - Jaffe, E S AU - Creekmore, S P AU - Longo, D L AU - Kwak, L W AD - Department of Experimental Transplantation and Immunology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland, USA, kwak@mail.ncifcrf.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 1171 EP - 1178 VL - 5 IS - 10 SN - 1078-8956, 1078-8956 KW - man KW - immunology KW - cancer vaccines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antigen (tumor-associated) KW - Granulocyte-macrophage colony-stimulating factor KW - Vaccines KW - Lymphoma KW - F 06867:Lymphoma KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17419269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Complete+molecular+remissions+induced+by+patient-specific+vaccination+plus+granulocyte-monocyte+colony-stimulating+factor+against+lymphoma&rft.au=Bendandi%2C+M%3BGocke%2C+C+D%3BKobrin%2C+C+B%3BBenko%2C+F+A%3BSternas%2C+LA%3BPennington%2C+R%3BWatson%2C+T+M%3BReynolds%2C+C+W%3BGause%2C+B+L%3BDuffey%2C+P+L%3BJaffe%2C+E+S%3BCreekmore%2C+S+P%3BLongo%2C+D+L%3BKwak%2C+L+W&rft.aulast=Bendandi&rft.aufirst=M&rft.date=1999-10-01&rft.volume=5&rft.issue=10&rft.spage=1171&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/10.1038%2F13928 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccines; Granulocyte-macrophage colony-stimulating factor; Lymphoma; Antigen (tumor-associated) DO - http://dx.doi.org/10.1038/13928 ER - TY - JOUR T1 - Enzyme Prodrug Gene Therapy: Synergistic Use of the Herpes Simplex Virus-Cellular Thymidine Kinase/Ganciclovir System and Thymidylate Synthase Inhibitors for the Treatment of Colon Cancer AN - 17404211; 4637169 AB - The goal of this study was to improve the therapeutic index of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) system by the addition of thymidylate synthase (TS) inhibitors. For this, we assessed the potential of GCV to synergistically interact with 5-fluorouracil (5-FU), ZD1694 (Tomudex), and (E)-5-(2-bromovinyl)-2'-deoxyuridine in HSV-tk-expressing murine MC38 STK and human HT-29 STK colon carcinoma cell lines. Synergistic cell killing was observed in a clonogenic assay over most of the cytotoxic dose range by the median-effect principle of Chou and Talalay. In a s.c. HT-29 STK xenograft tumor' model, we demonstrated that the combination of GCV and 5-FU resulted in statistically significant enhanced animal survival over single-agent treatment. Furthermore, we showed that the combination of GCV and ZD1694 in association with the HSV-tk/GCV system was at least as effective as GCV/5-FU in vitro and in vivo. The mechanism for the observed synergy is most likely attributable to the increased GCV phosphorylation in the presence of the tested TS inhibitors. Our data suggest that the HSV-tk/GCV metabolic suicide gene transfer system could serve as an adjuvant of the presently used TS inhibitors, thus potentially improving the efficacy of present cancer gene therapy approaches. JF - Cancer Research AU - Wildner, O AU - Blaese, R M AU - Candotti, F AD - NIH, 10 Center Drive, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA, owildner@nhgri.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 5233 EP - 5238 VL - 59 IS - 20 SN - 0008-5472, 0008-5472 KW - mice KW - man KW - HSV KW - (E)-5-(2-bromovinyl)-2'-deoxyuridine KW - 5-fluorouracil KW - Herpes simplex virus KW - ZD1694 KW - ganciclovir KW - tk gene KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Thymidine kinase KW - Tumors KW - Thymidylate synthase KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17404211?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Enzyme+Prodrug+Gene+Therapy%3A+Synergistic+Use+of+the+Herpes+Simplex+Virus-Cellular+Thymidine+Kinase%2FGanciclovir+System+and+Thymidylate+Synthase+Inhibitors+for+the+Treatment+of+Colon+Cancer&rft.au=Wildner%2C+O%3BBlaese%2C+R+M%3BCandotti%2C+F&rft.aulast=Wildner&rft.aufirst=O&rft.date=1999-10-01&rft.volume=59&rft.issue=20&rft.spage=5233&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Herpes simplex virus; Gene therapy; Thymidine kinase; Thymidylate synthase; Tumors ER - TY - JOUR T1 - Comparative Studies of a Retrovirus versus a Poxvirus Vector in whole Tumor-Cell Vaccines AN - 17403803; 4637173 AB - A number of experimental and clinical studies have used retroviral vectors to express transgenes in whole tumor-cell vaccines. Recently, poxvirus vectors such as vaccinia or avipox have been used toward this goal. The studies reported here compare for the first time the use of a retroviral vector versus a poxvirus vector (vaccinia) in whole tumor-cell vaccines. The transgene used was the T-cell costimulatory molecule B7-1, and the tumor was the weakly or nonimmunogenic MC38 murine colon adenocarcinoma. Recombinant retrovirus (R-B7) and the recombinant vaccinia (V-B7) induced equivalent expression of B7 on the surface of the carcinoma cell. Using live whole-tumor cells as vaccine, cells transduced via recombinant retrovirus (MC38/R-B7) and recombinant vaccinia (MC38/V-B7) equally induced protection against challenge by native MC38 cells 14 days later. Upon rechallenge with native MC38 cells 40 days later, however, the MC38/R-B7 vaccine was shown to be less effective than the MC38/V-B7 vaccine. Similar results were obtained when the tumor cells were irradiated prior to administration. When comparative studies were conducted in which X-irradiated tumor-cell vaccines were given to mice bearing experimental lung metastases, the MC38/V-B7 vaccine was shown to be significantly (P = 0.0351) more effective than the MC38/R-B7 vaccine. Additional studies were carried out in mice that had received vaccinia virus previously. Again, the X-irradiated MC38/V-B7 vaccine was statistically (P = 0.024) more effective than the MC38/R-B7 vaccine in the elimination of metastases. When the naive and vaccinia-immune mice for each vaccination group were combined for meta-analysis (n = 16), the MC38/V-B7 was significantly more effective than the MC38/R-B7 in the treatment of pulmonary metastases (P = 0.0014) in this model. These studies thus demonstrate for the first time that a whole tumor-cell vaccine (either live or X-irradiated) containing a vaccinia transgene is at least as efficient, and sometimes more efficient, in inducing antitumor effects compared with the same vaccine using a retrovirus to express the transgene. The implications for the clinical applications of such approaches are discussed. JF - Cancer Research AU - Hodge, J W AU - Schlom, J AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, 10 Center Drive, Room 8B07, Bethesda, MD 20892, USA, js141c@nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 5106 EP - 5111 VL - 59 IS - 20 SN - 0008-5472, 0008-5472 KW - mice KW - Poxvirus KW - Retrovirus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Vaccines KW - Tumor cells KW - Carcinoma KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17403803?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Comparative+Studies+of+a+Retrovirus+versus+a+Poxvirus+Vector+in+whole+Tumor-Cell+Vaccines&rft.au=Hodge%2C+J+W%3BSchlom%2C+J&rft.aulast=Hodge&rft.aufirst=J&rft.date=1999-10-01&rft.volume=59&rft.issue=20&rft.spage=5106&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumor cells; Vaccines; Expression vectors; Carcinoma ER - TY - JOUR T1 - In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues AN - 17400060; 4615662 AB - Two methylenecyclopropane nucleoside analogues with a phenylphosphoralaninate moiety, QYL-685 and QYL-609, exert potent and specific activities against human immunodeficiency virus type 1 strain LAI (HIV-1 sub(LAI)) and HIV-2 in vitro. In this study, we induced HIV-1 variants resistant to QYL-685 by exposing HIV-1 sub(LAI) to increasing concentrations of QYL-685. After 16 passages, the virus (HIV-1 sub(P16)) was less sensitive to QYL-685 (104-fold), QYL-609 (> 41-fold), and (-)- beta -2',3'-dideoxy-3'-thiacytidine (3TC) (> 1,100-fold) than was HIV-1 sub(LAI) and contained an M184I mutation. Two infectious clones, HIV-1 sub(M184I) and HIV-1 sub(M184V), were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1 sub(wt)). However, in the presence of QYL-685 (4 mu M), HIV-1 sub(M184I) and HIV-1 sub(M184V) showed greater fitness than HIV-1 sub(wt). These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1. JF - Antimicrobial Agents & Chemotherapy AU - Yoshimura, K AU - Feldman, R AU - Kodama, E AU - Kavlick, M F AU - Qiu, Y-L AU - Zemlicka, J AU - Mitsuya, H AD - Experimental Retrovirology Section, Medicine Branch, National Cancer Institute, Bldg. 10, Room 5A11, 9000 Rockville Pk., Bethesda, MD 20892, USA, hmitsuya@helix.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 2479 EP - 2483 VL - 43 IS - 10 SN - 0066-4804, 0066-4804 KW - QYL-609 KW - QYL-685 KW - Human immunodeficiency virus 1 KW - Methylenecyclopropane KW - methylenecyclopropane KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Antiviral agents KW - Drug resistance KW - Mutation KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01064:Microbial resistance KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17400060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=In+vitro+induction+of+human+immunodeficiency+virus+type+1+variants+resistant+to+phosphoralaninate+prodrugs+of+Z-methylenecyclopropane+nucleoside+analogues&rft.au=Yoshimura%2C+K%3BFeldman%2C+R%3BKodama%2C+E%3BKavlick%2C+M+F%3BQiu%2C+Y-L%3BZemlicka%2C+J%3BMitsuya%2C+H&rft.aulast=Yoshimura&rft.aufirst=K&rft.date=1999-10-01&rft.volume=43&rft.issue=10&rft.spage=2479&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Antiviral agents; Drug resistance; Mutation ER - TY - JOUR T1 - Genetic strategies to inhibit HIV AN - 17396304; 4622024 AB - The worldwide incidence of HIV infection continues to rise despite more than a decade of intense research aimed at developing effective intervention strategies. Because the mechanisms of action of the essential HIV gene products are now known, these have become potential targets for intervention. Some of these targets are attractive candidates for intervention by gene therapy. This review will focus on the recent progress in gene therapy strategies, including approaches approved for clinical trials. The efficacy of these various anti-HIV strategies, as well as the advantages and drawbacks of the different existing gene delivery systems, will be discussed. JF - Molecular Medicine Today AU - Morgan, R A AD - Gene Transfer Technology Section, Clinical Gene Therapy Branch/National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-1851, USA, rmorgan@nhgri.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 454 EP - 458 VL - 5 IS - 10 SN - 1357-4310, 1357-4310 KW - clinical trials KW - man KW - HIV KW - human immunodeficiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts; Virology & AIDS Abstracts KW - Gene therapy KW - Gene transfer KW - Human immunodeficiency virus KW - Reviews KW - Clinical trials KW - V 22002:AIDS: Molecular and in vitro aspects KW - G 07313:Viruses KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17396304?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Medicine+Today&rft.atitle=Genetic+strategies+to+inhibit+HIV&rft.au=Morgan%2C+R+A&rft.aulast=Morgan&rft.aufirst=R&rft.date=1999-10-01&rft.volume=5&rft.issue=10&rft.spage=454&rft.isbn=&rft.btitle=&rft.title=Molecular+Medicine+Today&rft.issn=13574310&rft_id=info:doi/10.1016%2FS1357-4310%2899%2901542-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Clinical trials; Gene therapy; Reviews; Gene transfer DO - http://dx.doi.org/10.1016/S1357-4310(99)01542-7 ER - TY - JOUR T1 - Outer membrane proteins as a carrier for detoxified lipooligosaccharide conjugate vaccines for nontypeable Haemophilus influenzae AN - 17343449; 4615075 AB - Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines. JF - Infection and Immunity AU - Wu, T-H AU - Gu, X-X AD - NIDCD, NIH, 5 Research Court, 2A31, Rockville, MD 20850, USA, guxx@nidcd.nih.gov Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 5508 EP - 5513 VL - 67 IS - 10 SN - 0019-9567, 0019-9567 KW - Haemophilus influenzae KW - Lipooligosaccharides KW - Omp protein KW - immunology KW - lipooligosaccharides KW - mice KW - oligosaccharides KW - rabbits KW - respiratory tract infection KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cell surface KW - Bactericidal activity KW - Antibody response KW - Otitis media KW - Proteins KW - Vaccines KW - Conjugates KW - W3 33365:Vaccines (other) KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization KW - A 01099:Bacteria and fungi KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17343449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Outer+membrane+proteins+as+a+carrier+for+detoxified+lipooligosaccharide+conjugate+vaccines+for+nontypeable+Haemophilus+influenzae&rft.au=Wu%2C+T-H%3BGu%2C+X-X&rft.aulast=Wu&rft.aufirst=T-H&rft.date=1999-10-01&rft.volume=67&rft.issue=10&rft.spage=5508&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Haemophilus influenzae; Otitis media; Proteins; Vaccines; Conjugates; Antibody response; Cell surface; Bactericidal activity ER - TY - JOUR T1 - Treatment with succinic anhydride improves the immunogenicity of Shigella flexneri type 2a O-specific polysaccharide-protein conjugates in mice AN - 17341090; 4615109 AB - Seroepidemiological data and a clinical trial with a Shigella sonnei O-specific polysaccharide (O-SP)-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate provide evidence that a critical level of immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies in serum confers protection against shigellosis. We evaluated the immunogenicity of conjugates whose carrier proteins and O-SPs were treated with succinic anhydride (SA), which reacts with amino groups at neutral pH to form amide-linked carboxyls (succinylation). Conjugates were synthesized with either of two genetically inactivated medically useful toxins, the diphtheria protein CRM9 or rEPA, bound to the O-SP of Shigella flexneri type 2a. Conjugates composed of the succinylated protein, succinylated O-SP, or both succinylated components were administered to mice by a clinically relevant scheme, and their levels of serum IgG anti-LPS and anti-proteins were assayed 7 days after the second and third injections. CRM9 served as a more immunogenic carrier than rEPA. Conjugates composed of succinylated components were more immunogenic than the conjugates composed of the native components. SA treatment of both the carrier protein and the O-SP did not confer an advantage over the succinylated protein alone. Conjugates prepared with native proteins, in general, elicited slightly higher levels of IgG protein antibodies than conjugates composed of the SA-treated proteins. JF - Infection and Immunity AU - Pavliakova, D AU - Chu, Ch AU - Bystricky, S AU - Tolson, N W AU - Shiloach, J AU - Kaufman, J B AU - Bryla, DA AU - Robbins, J B AU - Schneerson, R AD - National Institutes of Health, Building 6, Room 424, Bethesda, MD 20892-2720, USA Y1 - 1999/10// PY - 1999 DA - Oct 1999 SP - 5526 EP - 5529 VL - 67 IS - 10 SN - 0019-9567, 0019-9567 KW - Polysaccharides KW - Succinic anhydride KW - double prime O antigen KW - conjugates KW - mice KW - rEPA protein KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts B: Bacteriology KW - Antibody response KW - Toxins KW - Immunogenicity KW - Shigella flexneri KW - Vaccines KW - Conjugates KW - Pseudomonas aeruginosa KW - J 02834:Vaccination and immunization KW - A 01099:Bacteria and fungi UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17341090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Treatment+with+succinic+anhydride+improves+the+immunogenicity+of+Shigella+flexneri+type+2a+O-specific+polysaccharide-protein+conjugates+in+mice&rft.au=Pavliakova%2C+D%3BChu%2C+Ch%3BBystricky%2C+S%3BTolson%2C+N+W%3BShiloach%2C+J%3BKaufman%2C+J+B%3BBryla%2C+DA%3BRobbins%2C+J+B%3BSchneerson%2C+R&rft.aulast=Pavliakova&rft.aufirst=D&rft.date=1999-10-01&rft.volume=67&rft.issue=10&rft.spage=5526&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pseudomonas aeruginosa; Shigella flexneri; Toxins; Vaccines; Immunogenicity; Conjugates; Antibody response ER - TY - JOUR T1 - Inhibition of Bacterial Cell Wall-Induced Leukocyte Recruitment and Hepatic Granuloma Formation by TGF- beta Gene Transfer AN - 17336595; 4610767 AB - Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints. The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages. Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis. In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF- beta 1 i.m. to the SCW animals to determine the effect of TGF- beta 1 gene transfer on the course of liver inflammation and fibrosis. A single injection of plasmid DNA encoding TGF- beta 1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion. TGF- beta 1 DNA not only reduced key proinflammatory cytokines including TNF- alpha , IL-1 beta , IFN- gamma , and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver. Moreover, TGF- beta 1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals. Our study suggests that TGF- beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases. JF - Journal of Immunology AU - Song, Xiao-yu AU - Zeng, Li AU - Pilo, C M AU - Zagorski, J AU - Wahl, S M AD - Building 30, Room 332, 30 Convent Drive, MSC 4352, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4352, USA, smwahl@dir.nidcr.nih.gov Y1 - 1999/10/01/ PY - 1999 DA - 1999 Oct 01 SP - 4020 EP - 4026 VL - 163 IS - 7 SN - 0022-1767, 0022-1767 KW - Lewis rats KW - Streptococcus KW - immunology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Chemokines KW - Fibrosis KW - Cytokines KW - Leukocytes KW - Granuloma KW - Kupffer cells KW - Gene transfer KW - Liver KW - Cell walls KW - F 06774:Other cytokines (TNF, GM-CSF) KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17336595?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Inhibition+of+Bacterial+Cell+Wall-Induced+Leukocyte+Recruitment+and+Hepatic+Granuloma+Formation+by+TGF-+beta+Gene+Transfer&rft.au=Song%2C+Xiao-yu%3BZeng%2C+Li%3BPilo%2C+C+M%3BZagorski%2C+J%3BWahl%2C+S+M&rft.aulast=Song&rft.aufirst=Xiao-yu&rft.date=1999-10-01&rft.volume=163&rft.issue=7&rft.spage=4020&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cytokines; Leukocytes; Liver; Cell walls; Gene transfer; Fibrosis; Granuloma; Kupffer cells; Chemokines ER - TY - JOUR T1 - The AIDS epidemic: Considerations for the 21st century AN - 17409789; 4627326 AB - Humankind has been besieged throughout its evolution by microorganisms that pose a continual challenge to the survival of the species. Although such ancient killers as tuberculosis and malaria persistently take a toll of millions of lives per year, occasionally the emergence or reemergence of a microbe results in an unexpected, catastrophic pandemic with global public health consequences. As we prepare to leave the 20th century, it is worth reflecting on the fact that within the framework of an enormous but constant burden of a variety of infectious diseases, as well as a number of mini-epidemics, this century has witnessed two such unexpected cataclysmic events. One, the influenza A pandemic of 1918, was due to an old, but reemerging microbe. Influenza had been a problem for centuries, but in that one winter of 1918-1919, it was responsible for the deaths of approximately 25 million people worldwide and 550,000 people in the United States. The other pandemic, the acquired immunodeficiency syndrome (AIDS), is due to a newly recognized microbe, the human immunodeficiency virus (HIV). The world first became aware of this new disease in the summer of 1981, and it has exploded in successive waves in various regions of the world. Still, as we enter the 21st century, the catastrophic potential of the pandemic may still not have been fully realized. As we prepare to enter the new millennium, it is appropriate to reflect on the origins of this epidemic, what has occurred over the past 18 years, what has been accomplished from a scientific and public health perspective, and what the prospects are for the future. JF - New England Journal of Medicine AU - Fauci, A S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA, afauci@niaid.nih.gov Y1 - 1999/09/30/ PY - 1999 DA - 1999 Sep 30 SP - 1046 EP - 1050 VL - 341 IS - 14 SN - 0028-4793, 0028-4793 KW - man KW - HIV KW - Virology & AIDS Abstracts; Health & Safety Science Abstracts KW - Acquired immune deficiency syndrome KW - Epidemics KW - Human immunodeficiency virus KW - Public health KW - H 11000:Diseases/Injuries/Trauma KW - V 22005:AIDS: Epidemiological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17409789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=The+AIDS+epidemic%3A+Considerations+for+the+21st+century&rft.au=Fauci%2C+A+S&rft.aulast=Fauci&rft.aufirst=A&rft.date=1999-09-30&rft.volume=341&rft.issue=14&rft.spage=1046&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Acquired immune deficiency syndrome; Public health; Epidemics ER - TY - JOUR T1 - Slow transport of unpolymerized tubulin and polymerized neurofilament in the squid giant axon. AN - 70793503; 10500221 AB - A major issue in the slow transport of cytoskeletal proteins is the form in which they are transported. We have investigated the possibility that unpolymerized as well as polymerized cytoskeletal proteins can be actively transported in axons. We report the active transport of highly diffusible tubulin oligomers, as well as transport of the less diffusible neurofilament polymers. After injection into the squid giant axon, tubulin was transported in an anterograde direction at an average rate of 2.3 mm/day, whereas neurofilament was moved at 1.1 mm/day. Addition of the metabolic poisons cyanide or dinitrophenol reduced the active transport of both proteins to less than 10% of control values, whereas disruption of microtubules by treatment of the axon with cold in the presence of nocodazole reduced transport of both proteins to approximately 20% of control levels. Passive diffusion of these proteins occurred in parallel with transport. The diffusion coefficient of the moving tubulin in axoplasm was 8.6 micrometer(2)/s compared with only 0.43 micrometer(2)/s for neurofilament. These results suggest that the tubulin was transported in the unpolymerized state and that the neurofilament was transported in the polymerized state by an energy-dependent nocodazole/cold-sensitive transport mechanism. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Galbraith, J A AU - Reese, T S AU - Schlief, M L AU - Gallant, P E AD - Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4062, USA. jgalbrai@codon.nih.gov Y1 - 1999/09/28/ PY - 1999 DA - 1999 Sep 28 SP - 11589 EP - 11594 VL - 96 IS - 20 SN - 0027-8424, 0027-8424 KW - Neurofilament Proteins KW - 0 KW - Polymers KW - Tubulin KW - Index Medicus KW - Animals KW - Polymers -- metabolism KW - Diffusion KW - Decapodiformes KW - Biological Transport, Active KW - Axons -- metabolism KW - Tubulin -- metabolism KW - Neurofilament Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70793503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Slow+transport+of+unpolymerized+tubulin+and+polymerized+neurofilament+in+the+squid+giant+axon.&rft.au=Galbraith%2C+J+A%3BReese%2C+T+S%3BSchlief%2C+M+L%3BGallant%2C+P+E&rft.aulast=Galbraith&rft.aufirst=J&rft.date=1999-09-28&rft.volume=96&rft.issue=20&rft.spage=11589&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Physiol. 1976 Dec;263(2):115-37 [65468] J Cell Biol. 1975 Aug;66(2):351-66 [49355] J Cell Biol. 1996 Jun;133(6):1347-53 [8682869] Science. 1996 Aug 9;273(5276):784-8 [8670416] J Neurotrauma. 1997 Nov;14(11):811-22 [9421453] J Neurosci. 1998 Feb 1;18(3):821-9 [9437004] Curr Opin Cell Biol. 1998 Feb;10(1):87-92 [9484599] J Cell Biol. 1998 Oct 5;143(1):147-57 [9763427] J Cell Biol. 1999 Feb 8;144(3):447-58 [9971740] J Cell Biol. 1980 Aug;86(2):616-23 [6156946] Physiol Rev. 1980 Oct;60(4):1167-283 [6159657] J Cell Biol. 1982 Jan;92(1):192-8 [7199050] J Cell Biol. 1984 Jul;99(1 Pt 1):188-98 [6736127] J Cell Biol. 1984 Jul;99(1 Pt 2):212s-221s [6378920] J Cell Biol. 1984 Nov;99(5):1716-24 [6490717] Cell. 1985 Feb;40(2):455-62 [2578325] J Cell Biol. 1986 Sep;103(3):917-27 [3745275] Science. 1987 Jan 16;235(4786):337-9 [2432662] J Pharmacol Exp Ther. 1987 Jul;242(1):277-83 [2441026] J Cell Sci Suppl. 1986;5:161-79 [2443517] Brain Res. 1988 Feb 1;466(2):275-85 [2452001] J Neurosci. 1988 May;8(5):1479-84 [3130467] J Cell Biol. 1988 Aug;107(2):651-64 [3047145] Cell Motil Cytoskeleton. 1988;10(1-2):285-95 [3180248] Nature. 1990 Feb 1;343(6257):479-82 [1689016] Curr Opin Cell Biol. 1989 Feb;1(1):91-7 [2483519] J Neurosci. 1992 Jan;12(1):77-85 [1370324] J Cell Biol. 1992 Apr;117(1):105-20 [1556148] J Cell Biol. 1993 Mar;120(5):1177-86 [7679673] J Cell Biol. 1993 Apr;121(2):375-86 [8468352] Cell Motil Cytoskeleton. 1993;25(4):345-57 [8402955] Curr Opin Cell Biol. 1994 Feb;6(1):3-9 [8167023] J Cell Biol. 1994 Oct;127(1):173-85 [7929561] J Cell Sci. 1994 Aug;107 ( Pt 8):2291-8 [7527056] Neuron. 1995 Jun;14(6):1247-56 [7541635] J Cell Biol. 1995 Dec;131(5):1315-26 [8522592] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11500-3 [8524791] J Pharmacol Exp Ther. 1979 Mar;208(3):411-7 [85702] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Saccharomyces cerevisiae HCR1 gene encoding a homologue of the p35 subunit of human translation initiation factor 3 (eIF3) is a high copy suppressor of a temperature-sensitive mutation in the Rpg1p subunit of yeast eIF3. AN - 70048103; 10488093 AB - The complex eukaryotic initiation factor 3 (eIF3) was shown to promote the formation of the 43 S preinitiation complex by dissociating 40 S and 60 S ribosomal subunits, stabilizing the ternary complex, and aiding mRNA binding to 40 S ribosomal subunits. Recently, we described the identification of RPG1 (TIF32), the p110 subunit of the eIF3 core complex in yeast. In a screen for Saccharomyces cerevisiae multicopy suppressors of the rpg1-1 temperature-sensitive mutant, an unknown gene corresponding to the open reading frame YLR192C was identified. When overexpressed, the 30-kDa gene product, named Hcr1p, was able to support, under restrictive conditions, growth of the rpg1-1 temperature-sensitive mutant, but not of a Rpg1p-depleted mutant. An hcr1 null mutant was viable, but showed slight reduction of growth when compared with the wild-type strain. Physical interaction between the Hcr1 and Rpg1 proteins was shown by co-immunoprecipitation analysis. The combination of Deltahcr1 and rpg1-1 mutations resulted in a synthetic enhancement of the slow growth phenotype at a semipermissive temperature. In a computer search, a significant homology to the human p35 subunit of the eIF3 complex was found. We assume that the yeast Hcr1 protein participates in translation initiation likely as a protein associated with the eIF3 complex. JF - The Journal of biological chemistry AU - Valásek, L AU - Hasek, J AU - Trachsel, H AU - Imre, E M AU - Ruis, H AD - Vienna Biocenter, Institute of Biochemistry and Molecular Cell Biology, University of Vienna, A-1030 Vienna, Austria. lvalasek@aghmac1.nichd.nih.gov Y1 - 1999/09/24/ PY - 1999 DA - 1999 Sep 24 SP - 27567 EP - 27572 VL - 274 IS - 39 SN - 0021-9258, 0021-9258 KW - Cell Cycle Proteins KW - 0 KW - Eukaryotic Initiation Factor-3 KW - Fungal Proteins KW - HCR1 protein, S cerevisiae KW - Macromolecular Substances KW - Peptide Initiation Factors KW - Prokaryotic Initiation Factor-3 KW - RNA, Messenger KW - RPG1 protein, S cerevisiae KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Index Medicus KW - Gene Expression Regulation, Fungal KW - Ribosomes -- metabolism KW - Humans KW - Temperature KW - Amino Acid Sequence KW - Mutagenesis KW - Phenotype KW - Promoter Regions, Genetic KW - Sequence Alignment KW - RNA, Messenger -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Peptide Initiation Factors -- genetics KW - Fungal Proteins -- metabolism KW - Cell Cycle Proteins -- genetics KW - Saccharomyces cerevisiae -- growth & development KW - Repressor Proteins -- metabolism KW - Peptide Initiation Factors -- chemistry KW - Fungal Proteins -- genetics KW - Repressor Proteins -- genetics KW - Cell Cycle Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70048103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Saccharomyces+cerevisiae+HCR1+gene+encoding+a+homologue+of+the+p35+subunit+of+human+translation+initiation+factor+3+%28eIF3%29+is+a+high+copy+suppressor+of+a+temperature-sensitive+mutation+in+the+Rpg1p+subunit+of+yeast+eIF3.&rft.au=Val%C3%A1sek%2C+L%3BHasek%2C+J%3BTrachsel%2C+H%3BImre%2C+E+M%3BRuis%2C+H&rft.aulast=Val%C3%A1sek&rft.aufirst=L&rft.date=1999-09-24&rft.volume=274&rft.issue=39&rft.spage=27567&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of the cysteine residues in the amino-terminal extracellular domain of the human Ca(2+) receptor critical for dimerization. Implications for function of monomeric Ca(2+) receptor. AN - 70043784; 10488104 AB - We analyzed the effect of substituting serine for each of the 19 cysteine residues within the amino-terminal extracellular domain of the human Ca(2+) receptor on cell surface expression and receptor dimerization. C129S, C131S, C437S, C449S, and C482S were similar to wild type receptor; the other 14 cysteine to serine mutants were retained intracellularly. Four of these, C60S, C101S, C358S and C395S, were unable to dimerize. A C129S/C131S double mutant failed to dimerize but was unique in that the monomeric form expressed at the cell surface. Substitution of a cysteine for serine 132 within the C129S/C131S mutant restored receptor dimerization. Mutation of residues Cys-129, Cys-131, and Ser-132, singly and in various combinations caused a left shift in Ca(2+) response compared with wild type receptor. These results identify cysteines 129 and 131 as critical in formation of intermolecular disulfide bond(s) responsible for receptor dimerization. In a "venus flytrap" model of the receptor extracellular domain, Cys-129 and Cys-131 are located within a region protruding from one lobe of the flytrap. We suggest that this region represents a dimer interface for the receptor and that mutation of residues within the interface causes important changes in Ca(2+) response of the receptor. JF - The Journal of biological chemistry AU - Ray, K AU - Hauschild, B C AU - Steinbach, P J AU - Goldsmith, P K AU - Hauache, O AU - Spiegel, A M AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/09/24/ PY - 1999 DA - 1999 Sep 24 SP - 27642 EP - 27650 VL - 274 IS - 39 SN - 0021-9258, 0021-9258 KW - Calcium-Binding Proteins KW - 0 KW - Recombinant Proteins KW - Cysteine KW - K848JZ4886 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Immunoblotting KW - Protein Structure, Secondary KW - Models, Molecular KW - Dimerization KW - Humans KW - Amino Acid Sequence KW - Biotinylation KW - Rats KW - Mutagenesis, Site-Directed KW - Calcium -- metabolism KW - Sequence Alignment KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Cell Membrane -- metabolism KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Cell Line KW - Calcium-Binding Proteins -- genetics KW - Calcium-Binding Proteins -- metabolism KW - Calcium-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70043784?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+the+cysteine+residues+in+the+amino-terminal+extracellular+domain+of+the+human+Ca%282%2B%29+receptor+critical+for+dimerization.+Implications+for+function+of+monomeric+Ca%282%2B%29+receptor.&rft.au=Ray%2C+K%3BHauschild%2C+B+C%3BSteinbach%2C+P+J%3BGoldsmith%2C+P+K%3BHauache%2C+O%3BSpiegel%2C+A+M&rft.aulast=Ray&rft.aufirst=K&rft.date=1999-09-24&rft.volume=274&rft.issue=39&rft.spage=27642&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heterotopic endochondrial ossification with mixed tumor formation in C3(1)/Tag transgenic mice is associated with elevated TGF-beta1 and BMP-2 expression. AN - 70782001; 10498897 AB - Transgenic mice which express the simian virus 40 large T-antigen (Tag) under the regulatory control of the hormone responsive rat C3(1) gene develop unusual lesions of heterotopic bone growth associated with mixed tumor formation arising from eccrine sweat glands found only in the foot pads of mice, ischiocavernosus muscle adjacent to bulbourethral glands and occasionally the salivary and mammary glands. These lesions are very similar to mixed tumors arising in several types of human cancers. Based upon electron microscopic examination and immunocytochemical analyses of cellular differentiation markers, the mixed proliferative lesions in this transgenic mouse model begin with the Tag-induced proliferation of epithelial and myoepithelial cells. The proliferation of these two types of cells results in hyperplasia and adenomatous transformation of the epithelial component, whereas the proliferating myoepithelial cells undergo metaplasia to form chondrocytes which deposit extracellular matrix, including collagen fibers. Cartilage develops focally between areas of epithelial proliferation and subsequently ossifies through a process of endochondrial bone formation. The metaplasia of myoepithelial cells to chondrocytes appears to require the inductive interaction of factors produced by the closely associated proliferating epithelial cells, including members of the TGF-beta superfamily. We demonstrate that TGF-beta1 protein accumulates in the extracellular matrix of the lesions, whereas RNA in situ hybridization reveals that BMP-2, another strong inducer of heterotopic bone formation, is overexpressed by the proliferating epithelial cells during the development of ectopic bone. The formation of sarcomatous tumors within the mixed tumors appears to be androgen-dependent and more frequent in mice lacking a normal allele of p53. This process of cartilage and bone induction may mimic epithelial-mesenchymal interactions which occur during embryonic bone formation. These transgenic mice may provide new insights into the processes of ectopic endochondrial bone formation associated with mixed tumor formation and serve as a useful model for human heterotopic bone disease. JF - Oncogene AU - Maroulakou, I G AU - Shibata, M A AU - Anver, M AU - Jorcyk, C L AU - Liu, M l AU - Roche, N AU - Roberts, A B AU - Tsarfaty, I AU - Reseau, J AU - Ward, J AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, Bethesda, Maryland, MD 20892, USA. Y1 - 1999/09/23/ PY - 1999 DA - 1999 Sep 23 SP - 5435 EP - 5447 VL - 18 IS - 39 SN - 0950-9232, 0950-9232 KW - Actins KW - 0 KW - Androgen-Binding Protein KW - Antigens, Viral, Tumor KW - BMP2 protein, human KW - Bmp2 protein, mouse KW - Bmp2 protein, rat KW - Bone Morphogenetic Protein 2 KW - Bone Morphogenetic Proteins KW - EDA protein, human KW - Ectodysplasins KW - Eda protein, mouse KW - Gonadal Steroid Hormones KW - Membrane Proteins KW - PEBP1 protein, human KW - Phosphatidylethanolamine Binding Protein KW - Proliferating Cell Nuclear Antigen KW - Prostatein KW - Psbpc1 protein, rat KW - Psbpc2 protein, rat KW - Scgb2a2 protein, rat KW - Secretoglobins KW - Transforming Growth Factor beta KW - Tumor Suppressor Protein p53 KW - Vimentin KW - Tolonium Chloride KW - 15XUH0X66N KW - Keratins KW - 68238-35-7 KW - Uteroglobin KW - 9060-09-7 KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Foot Diseases -- genetics KW - Antigens, Viral, Tumor -- analysis KW - Proliferating Cell Nuclear Antigen -- analysis KW - Membrane Proteins -- genetics KW - Mice, Transgenic KW - Tumor Suppressor Protein p53 -- analysis KW - In Situ Hybridization KW - Male KW - Neoplasms, Complex and Mixed -- physiopathology KW - Foot Diseases -- etiology KW - Antigens, Viral, Tumor -- genetics KW - Mice KW - Foot Diseases -- pathology KW - Keratins -- analysis KW - Neoplasms, Complex and Mixed -- genetics KW - Vimentin -- analysis KW - Neoplasms, Complex and Mixed -- ultrastructure KW - Gonadal Steroid Hormones -- physiology KW - Androgen-Binding Protein -- genetics KW - Actins -- analysis KW - Immunohistochemistry KW - Mutation KW - Female KW - Transforming Growth Factor beta -- biosynthesis KW - Ossification, Heterotopic -- genetics KW - Ossification, Heterotopic -- physiopathology KW - Transforming Growth Factor beta -- physiology KW - Ossification, Heterotopic -- pathology KW - Bone Morphogenetic Proteins -- physiology KW - Bone Morphogenetic Proteins -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70782001?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Heterotopic+endochondrial+ossification+with+mixed+tumor+formation+in+C3%281%29%2FTag+transgenic+mice+is+associated+with+elevated+TGF-beta1+and+BMP-2+expression.&rft.au=Maroulakou%2C+I+G%3BShibata%2C+M+A%3BAnver%2C+M%3BJorcyk%2C+C+L%3BLiu%2C+M+l%3BRoche%2C+N%3BRoberts%2C+A+B%3BTsarfaty%2C+I%3BReseau%2C+J%3BWard%2C+J%3BGreen%2C+J+E&rft.aulast=Maroulakou&rft.aufirst=I&rft.date=1999-09-23&rft.volume=18&rft.issue=39&rft.spage=5435&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-29 N1 - Date created - 1999-10-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Engraftment of Hematopoietic Progenitor Cells Transduced with the Fanconi Anemia Group C Gene (FANCC) AN - 17390946; 4620022 AB - Fanconi anemia (FA) is an autosomal recessive disorder that leads to aplastic anemia. Mutations in the FANCC gene account for 10-15% of cases. FA cells are abnormally sensitive to DNA-damaging agents such as mitomycin C (MMC). Transfection of normal FANCC into mutant cells corrects this hypersensitivity and improves their viability in vitro. Four FA patients, representing the three major FANCC mutation subgroups, were entered into a clinical trial of gene transduction aimed at correction of the hematopoietic defect. Three patients received three or four cycles of gene transfer, each consisting of one or two infusions of autologous hematopoietic progenitor cells that had been transduced ex vivo with a retroviral vector carrying the normal FANCC gene. Prior to infusion, the FANCC transgene was demonstrated in transduced CD34-enriched progenitor cells. After infusion, FANCC was also present transiently in peripheral blood (PB) and bone marrow (BM) cells. Function of the normal FANCC transgene was suggested by a marked increase in hematopoietic colonies measured by in vitro cultures, including colonies grown in the presence of MMC, after successive gene therapy cycles in all patients. Transient improvement in BM cellularity coincided with this expansion of hematopoietic progenitors. A fourth patient, who received a single infusion of transduced CD34-enriched BM cells, was given radiation therapy for a concurrent gynecologic malignancy. The FANCC transgene was detected in her PB and BM cells only after recovery from radiation-induced aplasia, suggesting that FANCC gene transduction confers a selective engraftment advantage. These experiments highlight both the potential and difficulties in applying gene therapy to FA. JF - Human Gene Therapy AU - Liu, J M AU - Kim, S AU - Read, E J AU - Futaki, M AU - Dokal, I AU - Carter, C S AU - Leitman, S F AU - Pensiero, M AU - Young, N S AU - Walsh, CE AD - Hematology Branch, National Heart, Lung, and Blood Institute, Bldg. 10, Rm. 7C103, ACRF, Bethesda, MD 20892, USA, LiuJ@gwgate.nhlbi.nih.gov Y1 - 1999/09/20/ PY - 1999 DA - 1999 Sep 20 SP - 2337 EP - 2346 VL - 10 IS - 14 SN - 1043-0342, 1043-0342 KW - man KW - clinical trials KW - CD34 antigen KW - FANCC gene KW - mitomycin C KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Radiation KW - Gene therapy KW - Gene transfer KW - Fanconi syndrome KW - Hemopoiesis KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17390946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Engraftment+of+Hematopoietic+Progenitor+Cells+Transduced+with+the+Fanconi+Anemia+Group+C+Gene+%28FANCC%29&rft.au=Liu%2C+J+M%3BKim%2C+S%3BRead%2C+E+J%3BFutaki%2C+M%3BDokal%2C+I%3BCarter%2C+C+S%3BLeitman%2C+S+F%3BPensiero%2C+M%3BYoung%2C+N+S%3BWalsh%2C+CE&rft.aulast=Liu&rft.aufirst=J&rft.date=1999-09-20&rft.volume=10&rft.issue=14&rft.spage=2337&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950016988 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Fanconi syndrome; Gene transfer; Hemopoiesis; Radiation DO - http://dx.doi.org/10.1089/10430349950016988 ER - TY - JOUR T1 - Clostridium septicum alpha toxin uses glycosylphosphatidylinositol-anchored protein receptors. AN - 70026424; 10480947 AB - The alpha toxin produced by Clostridium septicum is a channel-forming protein that is an important contributor to the virulence of the organism. Chinese hamster ovary (CHO) cells are sensitive to low concentrations of the toxin, indicating that they contain toxin receptors. Using retroviral mutagenesis, a mutant CHO line (BAG15) was generated that is resistant to alpha toxin. FACS analysis showed that the mutant cells have lost the ability to bind the toxin, indicating that they lack an alpha toxin receptor. The mutant cells are also resistant to aerolysin, a channel-forming protein secreted by Aeromonas spp., which is structurally and functionally related to alpha toxin and which is known to bind to glycosylphosphatidylinositol (GPI)-anchored proteins, such as Thy-1. We obtained evidence that the BAG15 cells lack N-acetylglucosaminyl-phosphatidylinositol deacetylase-L, needed for the second step in GPI anchor biosynthesis. Several lymphocyte cell lines lacking GPI-anchored proteins were also shown to be less sensitive to alpha toxin. On the other hand, the sensitivity of CHO cells to alpha toxin was increased when the cells were transfected with the GPI-anchored folate receptor. We conclude that alpha toxin, like aerolysin, binds to GPI-anchored protein receptors. Evidence is also presented that the two toxins bind to different subsets of GPI-anchored proteins. JF - The Journal of biological chemistry AU - Gordon, V M AU - Nelson, K L AU - Buckley, J T AU - Stevens, V L AU - Tweten, R K AU - Elwood, P C AU - Leppla, S H AD - Oral Infection and Immunity Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/09/17/ PY - 1999 DA - 1999 Sep 17 SP - 27274 EP - 27280 VL - 274 IS - 38 SN - 0021-9258, 0021-9258 KW - Bacterial Toxins KW - 0 KW - Carrier Proteins KW - Folate Receptors, GPI-Anchored KW - Glycosylphosphatidylinositols KW - Pore Forming Cytotoxic Proteins KW - Receptors, Cell Surface KW - aerolysin KW - 53126-24-2 KW - Type C Phospholipases KW - EC 3.1.4.- KW - Phosphatidylinositol Diacylglycerol-Lyase KW - EC 4.6.1.13 KW - Index Medicus KW - Animals KW - Carrier Proteins -- metabolism KW - Bacterial Toxins -- metabolism KW - Retroviridae KW - CHO Cells KW - Models, Chemical KW - Mutagenesis KW - Cricetinae KW - Clostridium -- metabolism KW - Glycosylphosphatidylinositols -- metabolism KW - Type C Phospholipases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70026424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Clostridium+septicum+alpha+toxin+uses+glycosylphosphatidylinositol-anchored+protein+receptors.&rft.au=Gordon%2C+V+M%3BNelson%2C+K+L%3BBuckley%2C+J+T%3BStevens%2C+V+L%3BTweten%2C+R+K%3BElwood%2C+P+C%3BLeppla%2C+S+H&rft.aulast=Gordon&rft.aufirst=V&rft.date=1999-09-17&rft.volume=274&rft.issue=38&rft.spage=27274&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-13 N1 - Date created - 1999-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential in vitro association of vinca alkaloid-induced tubulin spiral filaments into aggregated spirals. AN - 70787744; 10509748 AB - Vinblastine, vincristine, vindesine, and vinorelbine, the four vinca alkaloids used in cancer therapy, differ in their antitumoral spectra and toxicities, but not in their inhibitory effects on microtubule assembly in vitro. At higher drug concentrations, vinca alkaloids induce the assembly of spiral filaments of tubulin, which, in turn, can interact laterally and form paracrystals. Using methods that distinguish spiral filaments and paracrystals (aggregated spirals), we found that spiral filament formation was largely independent of the incubation temperature, of the alkaloid used, and of the presence or absence of microtubule-associated proteins (MAPs). In contrast, the formation of aggregated spirals was markedly dependent on the alkaloid used, on the incubation temperature, and on the absence or presence of MAPs. Aggregated spirals failed to assemble in the presence of high concentrations of MAP-1A or MAP-1B, whereas they assembled readily with tau and MAP-2. Differences in patterns of turbidity development using pure tubulin allowed the classification of thirteen cytotoxic vinca alkaloids into five distinct groups, with centrifugal recovery of aggregated spirals in close agreement with the various turbidity patterns. With microtubule protein, i.e. tubulin preparations containing MAPs, only four groups were defined by turbidity patterns, and centrifugal protein recovery was more divergent. Vinblastine, vincristine, vindesine, and vinorelbine fell into distinct groups under both reaction conditions, and thus they appear to have qualitatively distinguishable in vitro interactions with tubulin. These differential effects on spiral filament and aggregated spiral assembly revealed that the four drugs induce different constraints on the tubulin molecule. JF - Biochemical pharmacology AU - Verdier-Pinard, P AU - Garès, M AU - Wright, M AD - Institut de Pharmacologie et de Biologie Structurale, C.N.R.S. Toulouse, France. verdierp@dc37a.nci.nih.gov Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 959 EP - 971 VL - 58 IS - 6 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Microtubule Proteins KW - Microtubule-Associated Proteins KW - Tubulin KW - Vinca Alkaloids KW - S 12363 KW - 123286-01-1 KW - Index Medicus KW - Microtubule Proteins -- metabolism KW - Centrifugation KW - Animals KW - Microtubule-Associated Proteins -- metabolism KW - Sheep KW - Temperature KW - Tubulin -- drug effects KW - Vinca Alkaloids -- pharmacology KW - Tubulin -- chemistry KW - Antineoplastic Agents, Phytogenic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70787744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Differential+in+vitro+association+of+vinca+alkaloid-induced+tubulin+spiral+filaments+into+aggregated+spirals.&rft.au=Verdier-Pinard%2C+P%3BGar%C3%A8s%2C+M%3BWright%2C+M&rft.aulast=Verdier-Pinard&rft.aufirst=P&rft.date=1999-09-15&rft.volume=58&rft.issue=6&rft.spage=959&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-08 N1 - Date created - 1999-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sensitization of tumor necrosis factor alpha-resistant human melanoma by tumor-specific in vivo transfer of the gene encoding endothelial monocyte-activating polypeptide II using recombinant vaccinia virus. AN - 70061252; 10493523 AB - Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine with potent experimental antitumor activity. Its clinical use in cancer treatment is severely limited by its considerable toxicity after systemic administration, and it is currently confined to isolated limb and organ perfusion settings. In this report, we introduce a novel concept of TNF-alpha-based gene therapy using the TNF-sensitizing properties of endothelial cell monocyte-activating polypeptide II (EMAP-II). We hypothesized that transfer of the EMAP-II gene into established TNF-resistant human melanomas would render these tumors sensitive to subsequent systemic TNF-alpha treatment. To achieve tumor selective gene delivery, we constructed a recombinant vaccinia virus encoding the human EMAP-II gene (vvEMAP). In vitro transfection of human melanoma cells led to the production of EMAP-II by these cells. Supernatants of vvEMAP-transfected tumor cells mediated the induction of tissue factor in endothelial cells. We characterized the pattern of gene expression after systemic administration of a recombinant vaccinia virus encoding a reporter gene in a murine in vivo model of s.c. human melanoma. Gene expression in tumor tissue was increased 100-fold as compared with normal tissue, providing evidence for tumor-selective gene delivery. Finally, human melanomas in nude mice were sensitized in vivo by transferring the EMAP-II gene using vvEMAP. Subsequent systemic administration of TNF-alpha led to tumor regression and growth inhibition of these previously TNF-resistant tumors (P < 0.05). This approach using gene therapy to sensitize primarily unresponsive tumors toward TNF-alpha may enhance the usefulness of TNF-alpha in clinical treatment strategies by increasing the window for the therapeutic application of the cytokine, thus reducing the dose necessary for antitumor responses and subsequently reduce toxicity. JF - Cancer research AU - Gnant, M F AU - Berger, A C AU - Huang, J AU - Puhlmann, M AU - Wu, P C AU - Merino, M J AU - Bartlett, D L AU - Alexander, H R AU - Libutti, S K AD - Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 4668 EP - 4674 VL - 59 IS - 18 SN - 0008-5472, 0008-5472 KW - Culture Media, Conditioned KW - 0 KW - Cytokines KW - Growth Inhibitors KW - Neoplasm Proteins KW - RNA-Binding Proteins KW - Recombinant Proteins KW - Tumor Necrosis Factor-alpha KW - small inducible cytokine subfamily E, member 1 KW - Thromboplastin KW - 9035-58-9 KW - Luciferases KW - EC 1.13.12.- KW - Index Medicus KW - Animals KW - Growth Inhibitors -- genetics KW - Humans KW - Mice, Nude KW - Mice KW - Endothelium, Vascular -- physiology KW - Vaccinia virus KW - Tumor Cells, Cultured KW - Transfection KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Genes, Reporter KW - Thromboplastin -- genetics KW - Luciferases -- genetics KW - Growth Inhibitors -- physiology KW - Cell Line KW - Female KW - Tumor Necrosis Factor-alpha -- toxicity KW - Melanoma -- pathology KW - RNA-Binding Proteins -- genetics KW - Neoplasm Proteins -- physiology KW - Neoplasm Proteins -- genetics KW - RNA-Binding Proteins -- physiology KW - Skin Neoplasms -- therapy KW - Genetic Therapy KW - Drug Resistance, Neoplasm KW - Melanoma -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70061252?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Sensitization+of+tumor+necrosis+factor+alpha-resistant+human+melanoma+by+tumor-specific+in+vivo+transfer+of+the+gene+encoding+endothelial+monocyte-activating+polypeptide+II+using+recombinant+vaccinia+virus.&rft.au=Gnant%2C+M+F%3BBerger%2C+A+C%3BHuang%2C+J%3BPuhlmann%2C+M%3BWu%2C+P+C%3BMerino%2C+M+J%3BBartlett%2C+D+L%3BAlexander%2C+H+R%3BLibutti%2C+S+K&rft.aulast=Gnant&rft.aufirst=M&rft.date=1999-09-15&rft.volume=59&rft.issue=18&rft.spage=4668&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-08 N1 - Date created - 1999-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses. AN - 70052082; 10494451 AB - Heritable variation in brain monoaminergic activity has been suggested to lead to interindividual differences in vulnerability to alcoholism, and many other behavioral disorders. We evaluated if a functional Cys23Ser polymorphism in the 5-HT2C receptor gene, the principal serotonin receptor in the brain, contributes to variation in serotonin, norepinephrine and dopamine activity, as indexed by their major metabolite concentrations in cerebrospinal fluid (CSF). Genotype-monoamine metabolite concentration associations were subsequently correlated to risk for alcoholism. The study sample consisted of unrelated Finnish males, including 214 alcoholic, violent offenders and 222 population controls who were interviewed using the Structured Clinical Interview for DSM-III-R, blind rated for psychiatric diagnoses and typed for the HTR2C Cys23Ser polymorphism. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), the major metabolite of norepinephrine, and homovanillic acid (HVA), the major metabolite of dopamine were available from 195 individuals. The major finding in this study was that HTR2C CysSer23 significantly contributed to CSF MHPG concentrations (p = .012). Higher concentrations of CSF MHPG were observed both in alcoholic violent offenders and population controls with HTR2C Ser23 genotype. Despite the association of Cys23Ser to CSF MHPG, HTR2C genotype was not associated with alcoholism, nor with other psychiatric disorders present in this sample. We conclude that a functional HTR2C Cys23Ser polymorphism contributes to the interindividual genetic variation of CSF MHPG explaining 3% of the total variance. This finding suggests that 5-HT2C receptors are involved in the regulation of norepinephrine turnover in humans; however, HTR2C Cys23Ser does not appear to contribute to the risk of alcoholism, or its contribution to this complex and heterogenous disorder is too small to be detected by a sample of this size and structure. JF - Biological psychiatry AU - Lappalainen, J AU - Long, J C AU - Virkkunen, M AU - Ozaki, N AU - Goldman, D AU - Linnoila, M AD - Section of Population Genetics and Linkage, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA. Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 821 EP - 826 VL - 46 IS - 6 SN - 0006-3223, 0006-3223 KW - Biogenic Monoamines KW - 0 KW - Receptors, Serotonin KW - Methoxyhydroxyphenylglycol KW - 534-82-7 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Dopamine KW - VTD58H1Z2X KW - Norepinephrine KW - X4W3ENH1CV KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Humans KW - Dopamine -- metabolism KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Brain -- metabolism KW - Receptors, Serotonin -- metabolism KW - Alcoholism -- genetics KW - Genotype KW - Homovanillic Acid -- cerebrospinal fluid KW - Psychiatric Status Rating Scales KW - Methoxyhydroxyphenylglycol -- cerebrospinal fluid KW - Norepinephrine -- metabolism KW - Receptors, Serotonin -- genetics KW - Male KW - Biogenic Monoamines -- cerebrospinal fluid KW - Mental Disorders -- diagnosis KW - Polymorphism, Genetic -- genetics KW - Genes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70052082?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=HTR2C+Cys23Ser+polymorphism+in+relation+to+CSF+monoamine+metabolite+concentrations+and+DSM-III-R+psychiatric+diagnoses.&rft.au=Lappalainen%2C+J%3BLong%2C+J+C%3BVirkkunen%2C+M%3BOzaki%2C+N%3BGoldman%2C+D%3BLinnoila%2C+M&rft.aulast=Lappalainen&rft.aufirst=J&rft.date=1999-09-15&rft.volume=46&rft.issue=6&rft.spage=821&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-29 N1 - Date created - 1999-12-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Down-regulation of cyclin D1 by transcriptional repression in MCF-7 human breast carcinoma cells induced by flavopiridol. AN - 70051661; 10493518 AB - Flavopiridol is a novel flavonoid that induces cell cycle arrest at different stages of the cell cycle because of the inhibition of cyclin-dependent kinases (cdks). In previous studies from our laboratory, (B. A. Carlson et al., Cancer Res., 56: 2973-2978, 1996), we observed that exposure of the MCF-7 breast carcinoma cell line to flavopiridol resulted in G1-S arrest, which was associated with the loss of cdk4 and cdk2 activity by 24 h of exposure. Along with this inhibition, flavopiridol decreased total cyclin-D protein levels in this cell line. In this work, we demonstrate that using isoform-specific antibodies, flavopiridol induces an early (by 6 h) decrease in cyclin D1 protein levels. This decline is followed by a decline in cyclin D3 with no effect on cyclin D2 or cyclin E levels by 10 h. Furthermore, at early time points (up to 8 h), the activity of cdk4 and the expression of endogenous phosphorylated retinoblastoma species from intact cells exposed to flavopiridol are unchanged. Thus, the decline in cdk4 activity and the induction of retinoblastoma hypophosphorylation follows cyclin D1 decline. Turnover studies demonstrate that the half-life of cyclin D1 (approximately 30 min) is not shortened in flavopiridol-exposed cells, and that the turnover of cdk4-bound cyclin D1 is unaltered. However, steady-state levels of cyclin D1 mRNA display a significant decrease by 4 h of flavopiridol treatment, with total disappearance by 8 h. This mRNA decline is not abrogated by the presence of cycloheximide. Furthermore, we have found that flavopiridol specifically represses the activity of the full-length cyclin D1 promoter linked to a luciferase reporter gene. In summary, we have found that the flavopiridol-induced decline in cyclin D1 is an early event, specific and, at least in part, due to the transcriptional repression of the cyclin D1 promoter. These results extend our understanding of flavopiridol's action to include regulation of cyclin D1 transcription. JF - Cancer research AU - Carlson, B AU - Lahusen, T AU - Singh, S AU - Loaiza-Perez, A AU - Worland, P J AU - Pestell, R AU - Albanese, C AU - Sausville, E A AU - Senderowicz, A M AD - Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 4634 EP - 4641 VL - 59 IS - 18 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - Piperidines KW - Proto-Oncogene Proteins KW - RNA, Messenger KW - Cyclin D1 KW - 136601-57-5 KW - alvocidib KW - 45AD6X575G KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - CDK2 protein, human KW - CDK4 protein, human KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinase 4 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Cyclin-Dependent Kinases -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Breast Neoplasms KW - S Phase KW - RNA, Messenger -- genetics KW - Tumor Cells, Cultured KW - Half-Life KW - Kinetics KW - G1 Phase KW - Female KW - Transcription, Genetic -- drug effects KW - Cyclin D1 -- metabolism KW - Piperidines -- toxicity KW - Antineoplastic Agents -- toxicity KW - Cyclin D1 -- genetics KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Cell Cycle -- drug effects KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70051661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Down-regulation+of+cyclin+D1+by+transcriptional+repression+in+MCF-7+human+breast+carcinoma+cells+induced+by+flavopiridol.&rft.au=Carlson%2C+B%3BLahusen%2C+T%3BSingh%2C+S%3BLoaiza-Perez%2C+A%3BWorland%2C+P+J%3BPestell%2C+R%3BAlbanese%2C+C%3BSausville%2C+E+A%3BSenderowicz%2C+A+M&rft.aulast=Carlson&rft.aufirst=B&rft.date=1999-09-15&rft.volume=59&rft.issue=18&rft.spage=4634&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-08 N1 - Date created - 1999-10-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The future of organ and tissue transplantation: can T-cell costimulatory pathway modifiers revolutionize the prevention of graft rejection? AN - 70048466; 10493208 AB - Transplantation therapies have revolutionized care for patients with endstage organ (kidney, liver, heart, lung, and pancreatic beta-cell) failure, yet significant problems persist with treatments designed to prevent graft rejection. Antirejection therapies are not always effective, must be taken daily, and are both expensive and associated with well-known toxic effects. Recent advances have suggested that the immune system has more self-regulatory capability than previously appreciated. In this review, we discuss immune system function and new therapeutic agents that modify so-called costimulatory receptor signaling to support transplant function without generally suppressing the immune system. JF - JAMA AU - Harlan, D M AU - Kirk, A D AD - Navy Medical Research Center, NIDDK/Navy Transplantation and Autoimmunity Branch, and the Uniformed Service University of the Health Sciences, Bethesda, MD 20889, USA. Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 1076 EP - 1082 VL - 282 IS - 11 SN - 0098-7484, 0098-7484 KW - Antigens, CD KW - 0 KW - Ligands KW - Membrane Glycoproteins KW - Abridged Index Medicus KW - Index Medicus KW - Lymphocyte Activation KW - Transplantation Immunology KW - Antigen Presentation KW - Animals KW - Humans KW - Tissue Transplantation -- adverse effects KW - T-Lymphocytes -- physiology KW - Graft Rejection -- immunology KW - Organ Transplantation -- trends KW - Organ Transplantation -- adverse effects KW - Graft Rejection -- prevention & control KW - Tissue Transplantation -- trends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70048466?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=The+future+of+organ+and+tissue+transplantation%3A+can+T-cell+costimulatory+pathway+modifiers+revolutionize+the+prevention+of+graft+rejection%3F&rft.au=Harlan%2C+D+M%3BKirk%2C+A+D&rft.aulast=Harlan&rft.aufirst=D&rft.date=1999-09-15&rft.volume=282&rft.issue=11&rft.spage=1076&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-29 N1 - Date created - 1999-09-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gastrulation in zebrafish: what mutants teach us. AN - 70039384; 10479444 AB - A major approach to the study of development is to compare the phenotypes of normal and mutant individuals for a given genetic locus. Understanding the development of a complex metazoan therefore requires examination of many mutants. Relatively few organisms are being studied this way, and zebrafish is currently the best example of a vertebrate for which large-scale mutagenesis screens have successfully been carried out. The number of genes mutated in zebrafish that have been cloned expands rapidly, bringing new insights into a number of developmental pathways operating in vertebrates. Here, we discuss work on zebrafish mutants affecting gastrulation and patterning of the early embryo. Gastrulation is orchestrated by the dorsal organizer, which forms in a region where maternally derived beta-catenin signaling is active. Mutation in the zygotic homeobox gene bozozok disrupts the organizer genetic program and leads to severe axial deficiencies, indicating that this gene is a functional target of beta-catenin signaling. Once established, the organizer releases inhibitors of ventralizing signals, such as BMPs, and promotes dorsoanterior fates within all germ layers. In zebrafish, several mutations affecting dorsal-ventral (D/V) patterning inactivate genes functioning in the BMP pathway, stressing the central role of this pathway in the gastrula embryo. Cells derived from the organizer differentiate into several axial structures, such as notochord and prechordal mesoderm, which are thought to induce various fates in adjacent tissues, such as the floor plate, after the completion of gastrulation. Studies with mutants in nodal-related genes, in one-eyed pinhead, which is required for nodal signaling, and in the Notch pathway reveal that midline cell fate specification is, in fact, initiated during gastrulation. Furthermore, the organizer coordinates morphogenetic movements, and zebrafish mutants in T-box mesoderm-specific genes help clarify the mechanism of convergence movements required for the formation of axial and paraxial mesoderm. Copyright 1999 Academic Press. JF - Developmental biology AU - Kodjabachian, L AU - Dawid, I B AU - Toyama, R AD - National Institute of Child Health and Human Development, National Institutes of Health, Building 6B/Room 420, Bethesda, Maryland, 20892, USA. kodja@nih.gov Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 231 EP - 245 VL - 213 IS - 2 SN - 0012-1606, 0012-1606 KW - Index Medicus KW - Genes, Homeobox KW - Animals KW - Mutation KW - Gene Expression Regulation, Developmental KW - Gastrula KW - Zebrafish -- genetics KW - Zebrafish -- embryology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70039384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+biology&rft.atitle=Gastrulation+in+zebrafish%3A+what+mutants+teach+us.&rft.au=Kodjabachian%2C+L%3BDawid%2C+I+B%3BToyama%2C+R&rft.aulast=Kodjabachian&rft.aufirst=L&rft.date=1999-09-15&rft.volume=213&rft.issue=2&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Developmental+biology&rft.issn=00121606&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-20 N1 - Date created - 1999-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of dexamethasone on elevated cytokine mRNA levels in chemical-induced hippocampal injury. AN - 70008264; 10467263 AB - An acute administration of the hippocampal toxicant trimethyltin (TMT) produced a specific pattern of neuronal necrosis in dentate granule cells with accompanying astrogliosis and initiation of a cytokine response within 24 hours. The purpose of this study was to examine the effects of the anti-inflammatory agent, dexamethasone (DEX), on the pattern of cytokine expression and neuronal degeneration occurring after an acute TMT injection. Dexamethasone (0.2 mg/kg or 10 mg/kg) was administered to 21-day-old male mice 1 hour prior to an injection of TMT hydroxide (2.5 mg/kg, i.p.). Mice receiving 0.2 mg/kg DEX received a second injection 6 hours after TMT. Twenty-four hours later, neuronal necrosis and astrogliosis were assessed and found to be similar in animals treated with TMT, either in the presence or absence of dexamethasone. Pretreatment with dexamethasone failed to prevent the neurodegeneration and astrogliosis. The TMT-induced injury response was represented in elevations of mRNA levels for the injury-associated host response genes glial fibrillary acidic protein (GFAP), EB22/5.3, and intercellular adhesion molecule-1 (ICAM-1). The combination of DEX and TMT produced increased elevation in mRNA levels for EB22/5.3 and ICAM, while GFAP levels remained the same as with TMT alone. The injury response from TMT was accompanied by elevations in mRNA levels for the cytokines tumor necrosis factor (TNF) alpha, TNFbeta, and interleukin (IL)-1alpha. Treatment with dexamethasone prior to TMT resulted in significantly elevated levels of TNFalpha, TNFbeta, and IL-1alpha as compared to TMT alone. These data represent the inability of glucocorticoids to downregulate the injury response in rat hippocampus following a systemic injection of TMT and suggest a stimulation and "priming" of hippocampal cells by dexamethasone. JF - Journal of neuroscience research AU - Bruccoleri, A AU - Pennypacker, K R AU - Harry, G J AD - Neurotoxicology Group, Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 916 EP - 926 VL - 57 IS - 6 SN - 0360-4012, 0360-4012 KW - Anti-Inflammatory Agents KW - 0 KW - Cytokines KW - Neurotoxins KW - RNA, Messenger KW - Transcription Factor AP-1 KW - Trimethyltin Compounds KW - trimethyltin KW - 1631-73-8 KW - Dexamethasone KW - 7S5I7G3JQL KW - Ribonucleases KW - EC 3.1.- KW - Index Medicus KW - Animals KW - Gliosis -- metabolism KW - Analysis of Variance KW - Transcription Factor AP-1 -- metabolism KW - Mice KW - Trimethyltin Compounds -- toxicity KW - Neurotoxins -- toxicity KW - Gliosis -- pathology KW - Mice, Inbred Strains KW - Necrosis KW - Gliosis -- chemically induced KW - Male KW - Nerve Degeneration KW - Cytokines -- genetics KW - RNA, Messenger -- metabolism KW - Dexamethasone -- pharmacology KW - Hippocampus -- metabolism KW - Hippocampus -- pathology KW - Hippocampus -- drug effects KW - Anti-Inflammatory Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70008264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Effect+of+dexamethasone+on+elevated+cytokine+mRNA+levels+in+chemical-induced+hippocampal+injury.&rft.au=Bruccoleri%2C+A%3BPennypacker%2C+K+R%3BHarry%2C+G+J&rft.aulast=Bruccoleri&rft.aufirst=A&rft.date=1999-09-15&rft.volume=57&rft.issue=6&rft.spage=916&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Opiate receptor avidity is reduced bilaterally in rhesus monkeys unilaterally lesioned with MPTP. AN - 69914996; 10421709 AB - Opiate receptor avidity (unoccupied receptor density / the receptor dissociation constant), was measured in four animals with unilateral parkinsonian symptoms following MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine) infusions into the internal carotid of one side, and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[(18)F]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. PET studies of 6-[(18)F]-L-fluoro-L-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) in these parkinsonian animals, although documenting the primarily unilateral nature of the lesion, also demonstrated a milder loss of dopaminergic on the side opposite the infusion. Opiate receptor avidity was found to be reduced by 20-34% in the caudate, anterior putamen, thalamus, and amygdala of these primarily unilaterally MPTP-exposed animals, bilaterally with no statistically significant differences between the two sides. The affected regions are the same as those previously demonstrated to have a 30-35% loss in clinically recovered bilaterally MPTP-lesioned animals. These findings confirm that the opiate pathway can change in response to modest decreases in basal ganglia dopamine innervation. Thus, opiate pathway adaptation is likely to contribute to the dynamic changes in basal ganglia circuits that forestall the initial clinical manifestations of Parkinson's disease. In addition, opiate pathway(s) may contribute to the treatment responsiveness and progression of the disease either directly through effects on basal ganglia function or indirectly through effects on basal ganglia plasticity. Copyright 1999 Wiley-Liss, Inc. JF - Synapse (New York, N.Y.) AU - Cohen, R M AU - Carson, R E AU - Wyatt, R J AU - Doudet, D J AD - Laboratory of Cerebral Metabolism, National Institute of Health, Bethesda, Maryland 20892-4030, USA. bob@shiloh.nimb.nih.gov Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 282 EP - 288 VL - 33 IS - 4 SN - 0887-4476, 0887-4476 KW - Fluorine Radioisotopes KW - 0 KW - Narcotic Antagonists KW - Receptors, Opioid KW - Receptors, Opioid, kappa KW - Receptors, Opioid, mu KW - fluorodopa F 18 KW - 2C598205QX KW - Naltrexone KW - 5S6W795CQM KW - Dihydroxyphenylalanine KW - 63-84-3 KW - 6-deoxy-6-fluoronaltrexone KW - 669I3FR8VF KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Animals KW - Limbic System -- physiology KW - Receptors, Opioid, kappa -- metabolism KW - Organ Specificity KW - Basal Ganglia -- physiology KW - Receptors, Opioid, mu -- metabolism KW - Infusions, Parenteral KW - Cerebellum -- physiology KW - Dihydroxyphenylalanine -- analogs & derivatives KW - Narcotic Antagonists -- pharmacokinetics KW - Cerebral Cortex -- physiology KW - Receptors, Opioid, mu -- antagonists & inhibitors KW - Receptors, Opioid, kappa -- antagonists & inhibitors KW - Tomography, Emission-Computed KW - Macaca mulatta KW - Dihydroxyphenylalanine -- pharmacokinetics KW - Functional Laterality KW - Receptors, Opioid -- metabolism KW - Receptors, Opioid -- drug effects KW - Brain -- drug effects KW - Naltrexone -- analogs & derivatives KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- pharmacology KW - Naltrexone -- pharmacokinetics KW - Brain -- physiology KW - Brain -- diagnostic imaging KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69914996?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Opiate+receptor+avidity+is+reduced+bilaterally+in+rhesus+monkeys+unilaterally+lesioned+with+MPTP.&rft.au=Cohen%2C+R+M%3BCarson%2C+R+E%3BWyatt%2C+R+J%3BDoudet%2C+D+J&rft.aulast=Cohen&rft.aufirst=R&rft.date=1999-09-15&rft.volume=33&rft.issue=4&rft.spage=282&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-30 N1 - Date created - 1999-08-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal supplemental and dietary zinc intake and the occurrence of neural tube defects in California AN - 17576416; 4610923 AB - The authors investigated the association between maternal preconceptional supplemental and dietary zinc intake and risk of neural tube defects (NTDs) in a population-based case-control study conducted between 1989 and 1991 in California. Cases were 430 NTD-affected fetuses/infants, and controls were 429 randomly selected non-malformed infants. Mothers reported their preconceptional use of vitamin, mineral, and food supplements, and completed a 98-item food frequency questionnaire. Increased total preconceptional zinc intake was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.43, 0.99). Phytate intake, a constituent of the diet known to impede zinc absorption, appeared to modify the zinc - NTD association. In addition, increased servings of animal products, the most bioavailable food source of zinc, was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, OR = 0.49, 95% CI 0.32, 0.76). Risk estimates for zinc intake were changed little after controlling for multiple sociodemographic factors and total folate intake, but were attenuated after controlling for nutrients highly correlated with dietary sources of zinc, such as protein. In sum, the analyses indicate that risk of NTDs in infants and fetuses decreased with increasing maternal preconceptional zinc intake. However, it remains unclear whether increased zinc intake, or another nutrient or combination of nutrients highly correlated with zinc intake in the diet, is causally associated with reduced NTD risk. JF - American Journal of Epidemiology AU - Velie, E M AU - Block, G AU - Shaw, G M AU - Samuels, S J AU - Schaffer, D M AU - Kulldorff, M AD - National Cancer Institute, Nutritional Epidemiology Branch, Building EPS, Room 7026, 6120 Executive Plaza Blvd., MSC 232, Bethesda, MD 20892-7232, USA Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 605 EP - 616 VL - 150 IS - 6 SN - 0002-9262, 0002-9262 KW - man KW - USA, California KW - neural tube defects KW - Risk Abstracts; CSA Neurosciences Abstracts; Health & Safety Science Abstracts KW - Diets KW - Maternal effects KW - Dietary intake KW - Nutrition KW - Neural tube defects KW - Pregnancy KW - Zinc KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - N3 11045:Primates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17576416?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Maternal+supplemental+and+dietary+zinc+intake+and+the+occurrence+of+neural+tube+defects+in+California&rft.au=Velie%2C+E+M%3BBlock%2C+G%3BShaw%2C+G+M%3BSamuels%2C+S+J%3BSchaffer%2C+D+M%3BKulldorff%2C+M&rft.aulast=Velie&rft.aufirst=E&rft.date=1999-09-15&rft.volume=150&rft.issue=6&rft.spage=605&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Diets; Zinc; Nutrition; Pregnancy; Maternal effects; Neural tube defects; Dietary intake ER - TY - JOUR T1 - Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer AN - 17028445; 4610917 AB - The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2,434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1,983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and greater than or equal to 40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates. JF - American Journal of Epidemiology AU - Cantor, K P AU - Lynch, C F AU - Hildesheim, ME AU - Dosemeci, M AU - Lubin, J AU - Alavanja, M AU - Craun, G AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., EPS 8106, Bethesda, MD 20892-7240, USA Y1 - 1999/09/15/ PY - 1999 DA - 1999 Sep 15 SP - 552 EP - 560 VL - 150 IS - 6 SN - 0002-9262, 0002-9262 KW - man KW - USA, Iowa KW - trihalomethanes KW - Water Resources Abstracts; Toxicology Abstracts; CSA Neurosciences Abstracts; Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Public health KW - Trihalomethane KW - Glioma KW - Brain KW - Surveys KW - Epidemiology KW - Byproducts KW - Public Health KW - Drinking Water KW - Water treatment KW - Multivariate analysis KW - Water Treatment KW - Water pollution KW - Cancer KW - Brain tumors KW - Risk KW - Trihalomethanes KW - Carcinogenesis KW - Chlorination KW - Drinking water KW - X 24120:Food, additives & contaminants KW - H 3000:Environment and Ecology KW - N3 11129:Neural and glial oncology KW - SW 3060:Water treatment and distribution KW - R2 23060:Medical and environmental health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17028445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Epidemiology&rft.atitle=Drinking+water+source+and+chlorination+byproducts+in+Iowa.+III.+Risk+of+brain+cancer&rft.au=Cantor%2C+K+P%3BLynch%2C+C+F%3BHildesheim%2C+ME%3BDosemeci%2C+M%3BLubin%2C+J%3BAlavanja%2C+M%3BCraun%2C+G&rft.aulast=Cantor&rft.aufirst=K&rft.date=1999-09-15&rft.volume=150&rft.issue=6&rft.spage=552&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Drinking Water; Chlorination; Byproducts; Epidemiology; Trihalomethanes; Surveys; Risk; Water Treatment; Public Health; Drinking water; Water treatment; Brain; Cancer; Public health; Carcinogenesis; Water pollution; Multivariate analysis; Glioma; Trihalomethane; Brain tumors ER - TY - JOUR T1 - X-linked Charcot-Marie-Tooth disease and connexin32. AN - 69340047; 10586227 AB - X-linked Charcot-Marie-Tooth disease is caused by mutations in the gene for the gap junction protein connexin32. This protein is expressed in peripheral nerve and present in noncompacted myelin, where it likely forms channels around and across the myelin sheath. Studies in cell culture and in transgenic mice show that connexin32 mutations can cause a loss of channel function or a gain of toxic effects on myelinating Schwann cells or both, with resulting peripheral nerve degeneration. JF - Annals of the New York Academy of Sciences AU - Fischbeck, K H AU - Abel, A AU - Lin, G S AU - Scherer, S S AD - Neurogenetics Branch, National Institute of Neurological Disease and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. kf@codon.nih.gov Y1 - 1999/09/14/ PY - 1999 DA - 1999 Sep 14 SP - 36 EP - 41 VL - 883 SN - 0077-8923, 0077-8923 KW - Connexins KW - 0 KW - connexin 32 KW - Index Medicus KW - Animals KW - Gap Junctions -- physiology KW - Humans KW - Mice KW - Gap Junctions -- genetics KW - Mice, Transgenic KW - Chromosome Mapping KW - Schwann Cells -- pathology KW - Charcot-Marie-Tooth Disease -- physiopathology KW - X Chromosome KW - Mutation KW - Charcot-Marie-Tooth Disease -- genetics KW - Connexins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69340047?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=X-linked+Charcot-Marie-Tooth+disease+and+connexin32.&rft.au=Fischbeck%2C+K+H%3BAbel%2C+A%3BLin%2C+G+S%3BScherer%2C+S+S&rft.aulast=Fischbeck&rft.aufirst=K&rft.date=1999-09-14&rft.volume=883&rft.issue=&rft.spage=36&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-21 N1 - Date created - 1999-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the Dlx3 homeobox gene upon differentiation of mouse keratinocytes. AN - 70009237; 10473625 AB - The Distal-less Dlx3 homeodomain gene is expressed in terminally differentiated murine epidermal cells, and there is evidence to support an essential role as a transcriptional regulator of the terminal differentiation process in these cells. In an attempt to determine the factors that induce Dlx3 gene expression, we have cloned the 1.2-kilobase pair proximal region of murine gene and analyzed its cis-regulatory elements and potential trans-acting factors. The proximal region of the Dlx3 gene has a canonical TATA box and CCAAT box, and the transcription start site was located 205 base pairs upstream from the initiation of translation site. Serial deletion analysis showed that the region between -84 and -34 confers the maximal promoter activity both in undifferentiated and differentiated primary mouse keratinocytes. Gel retardation assays and mutational analysis demonstrated that the transcriptional regulator NF-Y (also referred to as CBF) binds to a CCAAT box motif within this region and is responsible for the majority of the Dlx3 promoter activity. In addition, an Sp1-binding site was located immediately upstream of transcription start site that acts as a positive regulatory element of the Dlx3 promoter, independent of the CCAAT box motif. Importantly, elements residing between +30 to +60 of the Dlx3 gene are responsible for the Ca(2+)-dependent induction of Dlx3 during keratinocyte differentiation. JF - The Journal of biological chemistry AU - Park, G T AU - Morasso, M I AD - Laboratory of Skin Biology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/09/10/ PY - 1999 DA - 1999 Sep 10 SP - 26599 EP - 26608 VL - 274 IS - 37 SN - 0021-9258, 0021-9258 KW - CCAAT-Enhancer-Binding Proteins KW - 0 KW - DNA-Binding Proteins KW - Distal-less homeobox proteins KW - Homeodomain Proteins KW - Sp1 Transcription Factor KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Mice KW - Protein Binding KW - Cloning, Molecular KW - Calcium -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cells, Cultured KW - Sp1 Transcription Factor -- metabolism KW - Molecular Sequence Data KW - Sequence Deletion KW - DNA-Binding Proteins -- metabolism KW - Genes, Homeobox KW - Homeodomain Proteins -- genetics KW - Transcription Factors -- metabolism KW - Homeodomain Proteins -- metabolism KW - Keratinocytes -- cytology KW - Cell Differentiation -- genetics KW - Gene Expression Regulation KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70009237?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Regulation+of+the+Dlx3+homeobox+gene+upon+differentiation+of+mouse+keratinocytes.&rft.au=Park%2C+G+T%3BMorasso%2C+M+I&rft.aulast=Park&rft.aufirst=G&rft.date=1999-09-10&rft.volume=274&rft.issue=37&rft.spage=26599&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-07 N1 - Date created - 1999-10-07 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF167581; GENBANK N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2250-4 [7907794] J Biol Chem. 1994 Mar 11;269(10):7443-9 [7510286] J Biol Chem. 1994 Aug 5;269(31):20020-5 [8051086] Curr Opin Genet Dev. 1994 Oct;4(5):725-36 [7531523] J Biol Chem. 1995 Jan 6;270(1):468-75 [7814413] J Biol Chem. 1994 Aug 12;269(32):20489-96 [7519609] Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1624-8 [7878029] Mech Dev. 1994 Dec;48(3):199-215 [7893603] Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3968-72 [7732014] J Biol Chem. 1995 May 5;270(18):10792-9 [7738016] J Biol Chem. 1995 May 26;270(21):12614-22 [7759510] Virology. 1995 Dec 1;214(1):256-8 [8525624] J Biol Chem. 1996 Feb 2;271(5):2731-9 [8576248] J Biol Chem. 1996 Feb 23;271(8):4561-8 [8626812] J Biol Chem. 1996 Jun 14;271(24):14485-91 [8662945] J Biol Chem. 1996 Jun 21;271(25):14727-33 [8663077] J Biol Chem. 1996 Jul 19;271(29):17296-303 [8663388] J Biol Chem. 1996 Sep 27;271(39):24105-14 [8798649] Virology. 1996 Oct 1;224(1):281-91 [8862423] Genomics. 1996 Dec 15;38(3):314-24 [8975708] J Cell Biol. 1996 Dec;135(6 Pt 2):1879-87 [8991098] Gene. 1997 Mar 10;187(1):55-61 [9073066] Mamm Genome. 1997 Apr;8(4):302-3 [9096128] Mol Cell Biol. 1997 Jun;17(6):3056-64 [9154804] Cell Growth Differ. 1997 Jul;8(7):811-20 [9218875] Mol Reprod Dev. 1997 Nov;48(3):301-9 [9322240] Mol Cell Endocrinol. 1997 Sep 19;132(1-2):13-23 [9324042] Hum Mol Genet. 1998 Mar;7(3):563-9 [9467018] J Biol Chem. 1998 Jun 26;273(26):16104-11 [9632663] J Biol Chem. 1998 Jul 17;273(29):18499-508 [9660819] J Biol Chem. 1998 Jul 24;273(30):19339-47 [9668124] J Biol Chem. 1998 Sep 18;273(38):24683-92 [9733767] Nucleic Acids Res. 1999 Feb 1;27(3):764-70 [9889271] Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 [6326095] J Invest Dermatol. 1985 Jun;84(6):508-12 [3998499] Nucleic Acids Res. 1985 Mar 11;13(5):1431-42 [2987824] Dev Biol. 1986 Mar;114(1):238-46 [3956863] Nucleic Acids Res. 1986 Nov 25;14(22):9117-32 [3786147] Cell. 1987 Sep 11;50(6):863-72 [3476205] J Biol Chem. 1988 Apr 25;263(12):5940-7 [3281949] Science. 1988 Jul 29;241(4865):582-5 [3399893] Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998-9002 [2461560] Nature. 1989 Mar 30;338(6214):432-4 [2564639] J Cell Biol. 1989 Sep;109(3):1207-17 [2475508] Proc Natl Acad Sci U S A. 1990 Jul;87(14):5378-82 [2196566] EMBO J. 1990 Oct;9(10):3119-27 [1698608] Nucleic Acids Res. 1991 May 11;19(9):2499 [2041787] Neuron. 1991 Aug;7(2):221-9 [1678612] Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7948-52 [1716766] New Biol. 1991 Dec;3(12):1183-94 [1687503] Annu Rev Immunol. 1992;10:13-49 [1590984] Genes Dev. 1992 Jun;6(6):991-1004 [1592265] Mol Cell Biol. 1992 Oct;12(10):4251-61 [1341900] Mol Cell Biol. 1992 Oct;12(10):4400-11 [1406629] Science. 1992 Oct 23;258(5082):607-14 [1411571] Nucleic Acids Res. 1992 Nov 11;20(21):5519-25 [1454515] J Cell Biol. 1993 Jan;120(1):217-25 [7678013] Science. 1993 Apr 2;260(5104):78-82 [7682011] Nucleic Acids Res. 1993 Apr 11;21(7):1527-32 [8479902] J Invest Dermatol. 1993 Nov;101(5):719-26 [8228334] Dev Biol. 1994 Mar;162(1):267-76 [7907299] Mol Cell Biol. 1994 May;14(5):3263-75 [7909356] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Steroid-induced conformational changes of rat glucocorticoid receptor cause altered trypsin cleavage of the putative helix 6 in the ligand binding domain. AN - 69311960; 10580842 AB - Steroid-induced changes in receptor protein conformation constitute a logical means of translating the variations in steroid structures into the observed array of whole cell biological activities. One conformational change in the rat glucocorticoid receptor (GR) can be readily discerned by following the ability of trypsin digestion to afford a 16-kDa fragment. This fragment is seen after proteolysis of steroid-free receptors but disappears in digests of either glucocorticoid- or antiglucocorticoid-bound receptors. The location of this cleavage site has now been located unambiguously as R651, in helix 6 of the ligand binding domain, by a combination of point mutagenesis, arginine specific protease digestion, and radiochemical sequencing. This 16-kDa species, corresponding to amino acids 652-795, was non-covalently associated with another, approximately 17-kDa species that was determined to be amino acids 518-651 after a comparison of co-immunoprecipitated fragments from wild type and two chimeric receptors. These assignments revise our earlier report of amino acids 537-673 being the 16-kDa fragment and suggest that sequences of the entire ligand binding domain are required for high affinity and specificity binding. This was supported by the observation that trypsin digestion of the steroid-free R651A mutant GR gave rise to the 30-kDa meroreceptor (amino acids 518-795), which displayed wild type affinity. This 30-kDa species is thus the smallest non-associated fragment of GR possessing wild type steroid binding affinity. This suggests that other GR regions do not influence steroid binding affinity. The above results are reminiscent of those observed for the estrogen receptor. However, unlike the estrogen receptor or the more closely related progesterone receptor, the precise proteolytic cleavage points of both the steroid-free and -bound GR fall within regions that are predicted, on the basis of X-ray crystal structures of related receptors, to be alpha-helical and resistant to proteolysis. Thus, the tertiary structure of the GR ligand binding domain may be distinctly different from that of estrogen and progesterone receptors. JF - Molecular and cellular endocrinology AU - Xu, M AU - Modarress, K J AU - Meeker, J E AU - Simons, S S AD - Steroid Hormones Section, NIDDK/LMCB, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/09/10/ PY - 1999 DA - 1999 Sep 10 SP - 85 EP - 100 VL - 155 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Ligands KW - 0 KW - Peptide Fragments KW - Receptors, Glucocorticoid KW - Recombinant Fusion Proteins KW - Dexamethasone KW - 7S5I7G3JQL KW - Trypsin KW - EC 3.4.21.4 KW - Index Medicus KW - Protein Biosynthesis KW - Animals KW - COS Cells KW - Models, Molecular KW - Dexamethasone -- pharmacology KW - Humans KW - Transcription, Genetic KW - Mice KW - Recombinant Fusion Proteins -- chemistry KW - Binding Sites KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Mutagenesis, Site-Directed KW - Protein Structure, Secondary -- drug effects KW - Recombinant Fusion Proteins -- drug effects KW - Peptide Fragments -- chemistry KW - Transfection KW - Dexamethasone -- pharmacokinetics KW - Kinetics KW - Peptide Fragments -- drug effects KW - Amino Acid Substitution KW - Receptors, Glucocorticoid -- chemistry KW - Trypsin -- metabolism KW - Protein Conformation -- drug effects KW - Receptors, Glucocorticoid -- metabolism KW - Receptors, Glucocorticoid -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69311960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+endocrinology&rft.atitle=Steroid-induced+conformational+changes+of+rat+glucocorticoid+receptor+cause+altered+trypsin+cleavage+of+the+putative+helix+6+in+the+ligand+binding+domain.&rft.au=Xu%2C+M%3BModarress%2C+K+J%3BMeeker%2C+J+E%3BSimons%2C+S+S&rft.aulast=Xu&rft.aufirst=M&rft.date=1999-09-10&rft.volume=155&rft.issue=1-2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-17 N1 - Date created - 1999-12-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 2-[18F]F-A-85380: a PET radioligand for alpha4beta2 nicotinic acetylcholine receptors. AN - 70814592; 10511429 AB - 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380), a ligand for nicotinic acetylcholine receptors (nAChRs) was evaluated in an in vitro binding assay with membranes of rat brain and in vivo by PET in Rhesus monkey brain. The ligand has high affinity for alpha4beta2 nAChRs (K(D)=50 pM), crosses the blood-brain barrier, and distributes in the monkey brain in a pattern consistent with that of alpha4beta2 nAChRs. The specific/non-specific binding ratio increased steadily, reaching a value of 3.3 in the thalamus at 4 h. The specific binding of 2-[18F]F-A-85380 was reversed by cytisine. These results, in combination with the data demonstrating low toxicity of 2-[18F]F-A-85380, indicate that this ligand shows promise for use with PET in human subjects. JF - Neuroreport AU - Chefer, S I AU - Horti, A G AU - Koren, A O AU - Gündisch, D AU - Links, J M AU - Kurian, V AU - Dannals, R F AU - Mukhin, A G AU - London, E D AD - Brain Imaging Center, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA. Y1 - 1999/09/09/ PY - 1999 DA - 1999 Sep 09 SP - 2715 EP - 2721 VL - 10 IS - 13 SN - 0959-4965, 0959-4965 KW - 2-fluoro-3-(2-azetidinylmethoxy)pyridine KW - 0 KW - Alkaloids KW - Azetidines KW - Azocines KW - Ligands KW - Pyridines KW - Quinolizines KW - Radiopharmaceuticals KW - Receptors, Nicotinic KW - cytisine KW - 53S5U404NU KW - Index Medicus KW - Rats KW - Animals KW - Thalamus -- metabolism KW - Cerebral Cortex -- metabolism KW - Alkaloids -- pharmacology KW - Macaca mulatta KW - Time Factors KW - Cerebellum -- metabolism KW - Azetidines -- antagonists & inhibitors KW - Radiopharmaceuticals -- pharmacokinetics KW - Azetidines -- pharmacokinetics KW - Receptors, Nicotinic -- metabolism KW - Radiopharmaceuticals -- metabolism KW - Pyridines -- pharmacokinetics KW - Azetidines -- metabolism KW - Radiopharmaceuticals -- antagonists & inhibitors KW - Tomography, Emission-Computed KW - Pyridines -- antagonists & inhibitors KW - Pyridines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70814592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroreport&rft.atitle=2-%5B18F%5DF-A-85380%3A+a+PET+radioligand+for+alpha4beta2+nicotinic+acetylcholine+receptors.&rft.au=Chefer%2C+S+I%3BHorti%2C+A+G%3BKoren%2C+A+O%3BG%C3%BCndisch%2C+D%3BLinks%2C+J+M%3BKurian%2C+V%3BDannals%2C+R+F%3BMukhin%2C+A+G%3BLondon%2C+E+D&rft.aulast=Chefer&rft.aufirst=S&rft.date=1999-09-09&rft.volume=10&rft.issue=13&rft.spage=2715&rft.isbn=&rft.btitle=&rft.title=Neuroreport&rft.issn=09594965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-02 N1 - Date created - 1999-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer risk following radiotherapy for infertility or menstrual disorders. AN - 69965456; 10446443 AB - A cohort of 968 Israeli women treated with radiotherapy for infertility was followed up for cancer incidence. The majority of the subjects were irradiated to both the ovaries and the pituitary gland. Mean doses to the brain, colon, ovary and bone marrow were 0. 8, 0.6, 1.0 and 0.4 Gy, respectively. More than 10 years after radiation treatment, 60 cancers were observed compared with 74.5 expected based on national cancer incidence rates (standardized incidence ratio 0.81, 95% confidence interval 0.61-1.04). No statistically significant excess or deficit was seen for any individual type of cancer; however, a non-significant 60% increased risk of colon cancer was observed. Risk of colon cancer was higher among women with 2 or more treatments and increased with length of follow-up. A decreased risk of breast cancer was suggested. Neither age at exposure nor attained age modified subsequent cancer risk. No clear excess of any cancer site was observed among women at organ doses above the median compared with subjects at doses below the median, except a slight increase in colon cancer. No significant excess incidence of cancer was demonstrated in this small cohort of patients treated with radiotherapy for infertility. Our results are consistent with those from an earlier study of cancer mortality among women receiving radiotherapy for infertility conducted in New York City. Int. J. Cancer 82:795-798, 1999. Published 1999 Wiley-Liss, Inc. JF - International journal of cancer AU - Ron, E AU - Auvinen, A AU - Alfandary, E AU - Stovall, M AU - Modan, B AU - Werner, A AD - National Cancer Institute, Radiation Epidemiology Branch, Bethesda, MD, USA. rone@epndce.nci.nihi.gov Y1 - 1999/09/09/ PY - 1999 DA - 1999 Sep 09 SP - 795 EP - 798 VL - 82 IS - 6 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Israel -- epidemiology KW - Colon -- radiation effects KW - Brain -- radiation effects KW - Humans KW - Breast Neoplasms -- epidemiology KW - Pituitary Gland -- radiation effects KW - Risk Assessment KW - Ovary -- radiation effects KW - Colonic Neoplasms -- epidemiology KW - Genital Neoplasms, Female -- epidemiology KW - Risk Factors KW - Adult KW - Cohort Studies KW - Confidence Intervals KW - Incidence KW - Female KW - Amenorrhea -- radiotherapy KW - Neoplasms -- epidemiology KW - Menstruation Disturbances -- radiotherapy KW - Infertility, Female -- radiotherapy KW - Radiotherapy -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69965456?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Cancer+risk+following+radiotherapy+for+infertility+or+menstrual+disorders.&rft.au=Ron%2C+E%3BAuvinen%2C+A%3BAlfandary%2C+E%3BStovall%2C+M%3BModan%2C+B%3BWerner%2C+A&rft.aulast=Ron&rft.aufirst=E&rft.date=1999-09-09&rft.volume=82&rft.issue=6&rft.spage=795&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-10 N1 - Date created - 1999-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epidural resiniferatoxin induced prolonged regional analgesia to pain. AN - 70828663; 10517956 AB - Adequate treatment of cancer pain remains a significant clinical problem. To reduce side effects of treatment, intrathecal and epidural routes of administration have been used where appropriate to reduce the total dose of agent administered while achieving regional control. Resiniferatoxin (RTX), an ultrapotent capsaicin analog, gives long-term desensitization of nociception via C-fiber sensory neurons. We evaluate here the analgesic effect on rats of epidurally administered RTX, using latency of response to a thermal stimulus in unrestrained animals. Results were compared with those for systemically administered RTX. Vehicle or graded doses of RTX were injected subcutaneously (s.c.) or through an indwelling lumbar (L4) epidural catheter as a single dose. Both routes of application of RTX produced profound thermal analgesia, reaching a plateau within 4-6 h and showing no restoration of pain sensitivity over 7 days. Vehicle was without effect. For the epidural route, the effect was selective as expected for the targeted spinal cord region, whereas the subcutaneous administration of RTX had a generalized analgesic effect. At doses yielding a tripling of back paw withdrawal latency, epidural treatment was 25-fold more effective than the subcutaneous route of application. Consistent with the regional selectivity of the lumbar epidural route, the front paws showed no more effect than by systemic RTX treatment. Binding experiments with [3H]RTX provided further evidence of the segmental desensitization induced by epidural RTX. We conclude that epidural administration of RTX at the lumbar spinal level produces profound, long-lasting, segmental analgesia to C-fiber mediated pain in the rat. JF - Brain research AU - Szabo, T AU - Olah, Z AU - Iadarola, M J AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institute of Health, Bldg 37, Rm 3A01 9000 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 1999/09/04/ PY - 1999 DA - 1999 Sep 04 SP - 92 EP - 98 VL - 840 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Diterpenes KW - 0 KW - resiniferatoxin KW - A5O6P1UL4I KW - Index Medicus KW - Rats KW - Hot Temperature KW - Animals KW - Rats, Sprague-Dawley KW - Lumbosacral Region KW - Dose-Response Relationship, Drug KW - Injections, Subcutaneous KW - Pain Measurement KW - Time Factors KW - Male KW - Injections, Epidural KW - Reaction Time KW - Pain -- physiopathology KW - Diterpenes -- administration & dosage KW - Analgesia, Epidural KW - Diterpenes -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70828663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Epidural+resiniferatoxin+induced+prolonged+regional+analgesia+to+pain.&rft.au=Szabo%2C+T%3BOlah%2C+Z%3BIadarola%2C+M+J%3BBlumberg%2C+P+M&rft.aulast=Szabo&rft.aufirst=T&rft.date=1999-09-04&rft.volume=840&rft.issue=1-2&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Unconventional myosins and the genetics of hearing loss. AN - 85279645; pmid-10704189 AB - Mutations of the unconventional myosins genes encoding myosin VI, myosin VIIA and myosin XV cause hearing loss and thus these motor proteins perform fundamental functions in the auditory system. A null mutation in myosin VI in the congenitally deaf Snell's waltzer mice (Myo6(sv)) results in fusion of stereocilia and subsequent progressive loss of hair cells, beginning soon after birth, thus reinforcing the vital role of cytoskeletal proteins in inner ear hair cells. To date, there are no human families segregating hereditary hearing loss that show linkage to MYO6 on chromosome 6q13. The discovery that the mouse shaker1 (Myo7(ash1)) locus encodes myosin VIIA led immediately to the identification of mutations in this gene in Usher syndrome type 1B; subsequently, mutations in this gene were also found associated with recessive and dominant nonsyndromic hearing loss (DFNB2 and DFNA11). Stereocilla of sh1 mice are severely disorganized, and eventually degenerate as well. Myosin VIIA has been implicated in membrane trafficking and/or endocytosis in the inner ear. Mutant alleles of a third unconventional myosin, myosin XV, are associated with nonsyndromic, recessive, congenital deafness DFNB3 on human chromosome 17p11.2 and deafness in shaker2 (Myo15(sh2)) mice. In outer and inner hair cells, myosin XV protein is detectable in the cell body and stereocilia. Hair cells are present in homozygous sh2 mutant mice, but the stereocilia are approximately 1/10 of the normal length. This review focuses on what we know about the molecular genetics and biochemistry of myosins VI, VIIA and XV as relates to hereditary hearing loss. Am. J. Med. Genet. (Semin. Med. Genet.) 89:147-157, 1999. Published 2000 Wiley-Liss, Inc. JF - American Journal of Medical Genetics AU - Friedman, Thomas B AU - Sellers, J R AU - Avraham, K B AD - National Institute on Deafness and Other Communication Disorders PY - 1999 SP - 147 EP - 157 VL - 89 IS - 3 SN - 0148-7299, 0148-7299 KW - Deafness KW - Human KW - Myosins KW - Animal KW - Support, Non-U.S. Gov't KW - Support, U.S. Gov't, Non-P.H.S. KW - Mice KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85279645?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Unconventional+myosins+and+the+genetics+of+hearing+loss.&rft.au=Friedman%2C+Thomas+B%3BSellers%2C+J+R%3BAvraham%2C+K+B&rft.aulast=Friedman&rft.aufirst=Thomas&rft.date=1999-09-01&rft.volume=89&rft.issue=3&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. International Association for the Study of Pain. AN - 85261749; pmid-10488677 AB - The optimal assessment of cancer pain includes a detailed description of pain characteristics and classification by both syndrome and likely mechanisms. In the clinical setting, the interpretation of this information is aided by knowledge of the available clinical experiences on these aspects of the pain. Unfortunately, existing data are limited. There have been few large surveys of cancer pain characteristics and syndromes, and comparative data from patients in different parts of the world are entirely lacking. To better define the characteristics of cancer pain syndromes the Task Force on Cancer Pain of the International Association for the Study of Pain (IASP) conducted a prospective, cross-sectional, international, multicenter survey of pain specialists and their patients. From a total of 100 clinicians who described themselves as cancer pain practitioners in the IASP membership directory, 51 agreed to participate in the survey and a total of 58 provided data. These clinicians resided in 24 countries and evaluated a total of 1095 patients with severe cancer pain mostly requiring opioid medication, using a combination of patient-rated and observer-rated measures. The patient-rated scales comprised a pain intensity measure chosen from the brief pain inventory. The observer-rated information included demographic and tumor-related data, and responses on checklists of pain syndromes and pathophysiologies. Patients were heterogeneous in terms of demographics and tumor-related information. More than 76% had a Kamofsky performance status score or = 7 on a 10-point numeric scale. The factors that were univariately associated with higher pain intensity included the presence of breakthrough pain, somatic pain or neuropathic pain, age younger than 60 years, and lower performance status score. A multivariate model suggested that the presence of breakthrough pain, somatic pain, and lower performance status were the most important predictors of intense pain. Pains that were inferred by the treating clinician to be nociceptive and due to somatic injury occurred in 71.6% of the patients. Pains labeled nociceptive visceral were noted in 34.7% and pains inferred to have neuropathic mechanisms occurred in 39.7%. In a broad classification, the major pain syndromes comprised bone or joint lesions (41.7% of patients), visceral lesions (28.1%), soft tissue infiltration (28.3%), and peripheral nerve injuries (27.8%). Twenty-two types of pain syndromes were most prevalent. Large differences in the diagnosis of breakthrough pain by clinicians of different countries suggest that this phenomenon is either defined or recognized differently across countries. These data confirm, in segment of the cancer population experiencing severe pain, in different parts of the world, that cancer pain characteristics, syndromes and pathophysiologies are very heterogeneous. Predictors of worsening pain can be identified. The data provide a useful context for the interpretation of pain-related information acquired in both clinical and research settings. They suggest the need for future studies and the potential usefulness of a written checklist for cancer pain syndromes and pathophysiologies. JF - Pain AU - Caraceni, A AU - Portenoy, R K AD - Pain Therapy and Palliative Care Division, National Cancer Institute of Milan, Italy. PY - 1999 SP - 263 EP - 274 VL - 82 IS - 3 SN - 0304-3959, 0304-3959 KW - Cross-Sectional Studies KW - Neoplasms KW - Questionnaires KW - Human KW - Syndrome KW - Middle Age KW - Support, Non-U.S. Gov't KW - Female KW - Male KW - International Cooperation KW - Health Surveys KW - Pain Measurement UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85261749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=An+international+survey+of+cancer+pain+characteristics+and+syndromes.+IASP+Task+Force+on+Cancer+Pain.+International+Association+for+the+Study+of+Pain.&rft.au=Caraceni%2C+A%3BPortenoy%2C+R+K&rft.aulast=Caraceni&rft.aufirst=A&rft.date=1999-09-01&rft.volume=82&rft.issue=3&rft.spage=263&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Assistance from family members, friends, paid care givers, and volunteers in the care of terminally ill patients. AN - 85250919; pmid-10498492 AB - BACKGROUND: In addition to medical care, dying patients often need many types of assistance, including help with transportation, nursing care, homemaking services, and personal care. We interviewed terminally ill adults and their care givers in six randomly selected areas of the United States (five metropolitan areas and one rural county) to determine how their needs for assistance were met and the frequency with which they received such assistance from family members and paid and volunteer care givers. METHODS: The patients, whose physicians estimated them to have less than six months to live and who had clinically significant illness other than human immunodeficiency virus infection or the acquired immunodeficiency syndrome, were referred to the study by their physicians. Of the 1131 eligible patients, 988 (87.4 percent) consented to a detailed in-person interview conducted in English, as did 893 of the 915 eligible primary care givers (97.6 percent). RESULTS: Of the 988 terminally ill patients, 59.4 percent were over the age of 65 years, and 51.5 percent were women. The most frequent terminal illness was cancer (in 51.8 percent of the patients), followed by heart disease (18.0 percent) and chronic obstructive pulmonary disease (10.9 percent). Four percent of the patients were in an institution, such as a nursing home, residential hospice, or hospital; the rest were living in a private residence. A need for assistance was reported by 86.8 percent of the patients; they required help with transportation (reported by 62.0 percent), homemaking services (55.2 percent), nursing care (28.7 percent), and personal care (26.0 percent). Of the care givers, 72.1 percent were women. Primary care givers were family members in 96.0 percent of cases; only 4.0 percent were unrelated. Most patients relied completely on family members and friends for assistance. A total of 15.5 percent of patients relied only on paid assistance for more than half of the types of care that they needed. Volunteers (that is, unpaid helpers who were not family members or friends) provided less than 3 percent of all care. CONCLUSIONS: In our survey of terminally ill patients, family members, usually women, provided the majority of assistance with nonmedical care. Although many people received assistance from paid care givers, very few had assistance from volunteers. JF - The New England Journal of Medicine AU - Emanuel, E J AU - Fairclough, D L AU - Slutsman, J AU - Alpert, H AU - Baldwin, D AU - Emanuel, L L AD - Department of Clinical Bioethics, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1156, USA. PY - 1999 SP - 956 EP - 963 VL - 341 IS - 13 SN - 0028-4793, 0028-4793 KW - United States KW - Human KW - Terminally Ill KW - Home Care Services KW - Interpersonal Relations KW - Aged KW - Homemaker Services KW - Terminal Care KW - Caregivers KW - Family KW - Middle Age KW - Support, Non-U.S. Gov't KW - Data Collection KW - Voluntary Workers KW - Male KW - Female KW - Friends UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85250919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Assistance+from+family+members%2C+friends%2C+paid+care+givers%2C+and+volunteers+in+the+care+of+terminally+ill+patients.&rft.au=Emanuel%2C+E+J%3BFairclough%2C+D+L%3BSlutsman%2C+J%3BAlpert%2C+H%3BBaldwin%2C+D%3BEmanuel%2C+L+L&rft.aulast=Emanuel&rft.aufirst=E&rft.date=1999-09-01&rft.volume=341&rft.issue=13&rft.spage=956&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Hearing impairment data. AN - 85250073; pmid-10590758 JF - Public Health Reports (Washington, D.C. : 1974) AU - Battey, James F AD - National Institute on Deafness and Other Communication Disorders Y1 - 1999/09// PY - 1999 DA - September 1999 VL - 114 IS - 5 SN - 0033-3549, 0033-3549 KW - United States KW - Deafness KW - Human KW - Adult KW - Health Surveys KW - Aged KW - Middle Age KW - National Center for Health Statistics (U.S.) KW - Prevalence UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85250073?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Public+Health+Reports+%28Washington%2C+D.C.+%3A+1974%29&rft.atitle=Hearing+impairment+data.&rft.au=Battey%2C+James+F&rft.aulast=Battey&rft.aufirst=James&rft.date=1999-09-01&rft.volume=114&rft.issue=5&rft.spage=&rft.isbn=&rft.btitle=&rft.title=Public+Health+Reports+%28Washington%2C+D.C.+%3A+1974%29&rft.issn=00333549&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Examination of Low-Incidence Brain Tumor Responses in F344 Rats Following Chemical Exposures in National Toxicology Program Carcinogenicity Studies AN - 755137425; 13645994 AB - Neoplasms in the brain are uncommon in control Fischer 344 (F344) rats; they occur at a rate of less than 1% in 2-yr toxicity/ carcinogenicity studies. Furthermore, only 10 of nearly 500 studies conducted by the National Toxicology Program (NTP) showed any evidence of chemically related neoplastic effects in the brain. Generally, the brain tumor responses were considered equivocal, because the characteristics of potential neurocarcinogenic agents (such as statistically significant increased incidences, decreased latency and/or survival, and demonstration of dose-response relationships) were not observed. A thorough examination, including comparisons with a well-established historical database, is often critical in evaluating rare brain tumors. Chemicals that gave equivocal evidence of brain tumor responses were generally associated with carcinogenicity at other sites, and many chemicals were mutagenic when incubated with metabolic activating enzymes. Other factors that were supportive of the theory that marginal increases in brain tumor incidence were related to chemical exposure were that (a) some of the tumors were malignant, (b).no brain neoplasms were observed in concurrent controls from some studies, and/or (c) brain tumors were also seen following exposure to structurally related chemicals. In 2-yr studies in F344 rats (studies conducted by the NTP), equivocal evidence of carcinogenicity was observed for the following 9 chemicals: isoprene, bromoethane, chloroethane, 3,3'-dimethylbenzidine dihydrochloride, 3,3'-dimethoxybenzidine dihydrochloride, furosemide, C.I. direct blue 15, diphenhydramine hydrochloride, and 1-H-benzotriazole. Glycidol was the only chemical evaluated by the NTP with which there was clear evidence of brain tumor induction in F344 rats. Clarification of the potential neurocarcinogenic risks of chemicals that produce equivocal evidence of a brain tumor response in conventional 2-yr rodent studies may be aided by the use of transgenic mouse models that exhibit genetic alterations that reflect those present in human brain tumors as well as by the use of in utero exposures. JF - Toxicologic Pathology AU - Sills, Robert C AU - Hailey, James R AU - Neal, Jennifer AU - Boorman, Gary A AU - Haseman, Joseph K AU - Melnick, Ronald L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 589 EP - 599 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 27 IS - 5 SN - 0192-6233, 0192-6233 KW - CSA Neurosciences Abstracts; Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755137425?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Examination+of+Low-Incidence+Brain+Tumor+Responses+in+F344+Rats+Following+Chemical+Exposures+in+National+Toxicology+Program+Carcinogenicity+Studies&rft.au=Sills%2C+Robert+C%3BHailey%2C+James+R%3BNeal%2C+Jennifer%3BBoorman%2C+Gary+A%3BHaseman%2C+Joseph+K%3BMelnick%2C+Ronald+L&rft.aulast=Sills&rft.aufirst=Robert&rft.date=1999-09-01&rft.volume=27&rft.issue=5&rft.spage=589&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339902700513 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339902700513 ER - TY - JOUR T1 - The role of neoadjuvant and adjuvant chemotherapy regimens consisting of different combinations of drugs in the treatment of advanced oral cancer. AN - 70864930; 10523800 AB - We performed a retrospective analysis on the effect of neoadjuvant chemotherapy with three cycles of methotrexate (100 mg/m2 on day 1), cisplatin (90 mg/m2 on day 1) and bleomycin (20mg/m2 on day 1-5) with 21 d gap between each cycle in 44 patients with advanced squamous cell carcinoma of the cheek, lip and tongue followed by surgery and adjuvant chemotherapy consisting of cisplatin (90 mg/m2 on day 1), Mitomycin C (6 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 120 h continuous infusion from day 1) repeated every 3 weeks for three cycles. Following induction chemotherapy, complete response was observed in 11 out of 44 patients (25%), and a partial response in a further 28 patients (64%). The overall median survival of all patients was 29 months and those in stage III and stage IV were 30 and 15 months respectively (P< 0.001). The median duration of the time to relapse in patients who responded to adjuvant chemotherapy was 28 months. The main toxic effect was vomiting followed by hematological toxicity. No treatment-related deaths occurred. The regimen showed a significant response, encouraging median survival and a good tolerability profile. JF - Medical oncology (Northwood, London, England) AU - Basu, S AU - Khanra, M AU - Dash, B AU - Majumdar, J AU - Biswas, J AU - Chaudhuri, P AD - Department of Medical Oncology, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 199 EP - 203 VL - 16 IS - 3 SN - 1357-0560, 1357-0560 KW - Index Medicus KW - Survival Rate KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Secondary Prevention KW - Male KW - Female KW - Neoadjuvant Therapy -- methods KW - Mouth Neoplasms -- mortality KW - Carcinoma, Squamous Cell -- mortality KW - Chemotherapy, Adjuvant -- methods KW - Mouth Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Carcinoma, Squamous Cell -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70864930?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.atitle=The+role+of+neoadjuvant+and+adjuvant+chemotherapy+regimens+consisting+of+different+combinations+of+drugs+in+the+treatment+of+advanced+oral+cancer.&rft.au=Basu%2C+S%3BKhanra%2C+M%3BDash%2C+B%3BMajumdar%2C+J%3BBiswas%2C+J%3BChaudhuri%2C+P&rft.aulast=Basu&rft.aufirst=S&rft.date=1999-09-01&rft.volume=16&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.issn=13570560&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-24 N1 - Date created - 1999-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Emerging harmful algal blooms and human health: Pfiesteria and related organisms. AN - 70840600; 10528637 JF - Toxicologic pathology AU - Fleming, L E AU - Easom, J AU - Baden, D AU - Rowan, A AU - Levin, B AD - National Institute of Environmental Health Sciences Marine and Biomedical Sciences Center, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, Florida 33136, USA. lfleming@mednet.med.miami.edu PY - 1999 SP - 573 EP - 581 VL - 27 IS - 5 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Protozoan Infections -- parasitology KW - Environmental Monitoring KW - Plankton -- growth & development KW - Animals KW - Humans KW - Fish Diseases -- parasitology KW - Pfiesteria piscicida KW - Eukaryota -- growth & development KW - Public Health -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70840600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Emerging+harmful+algal+blooms+and+human+health%3A+Pfiesteria+and+related+organisms.&rft.au=Fleming%2C+L+E%3BEasom%2C+J%3BBaden%2C+D%3BRowan%2C+A%3BLevin%2C+B&rft.aulast=Fleming&rft.aufirst=L&rft.date=1999-09-01&rft.volume=27&rft.issue=5&rft.spage=573&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-17 N1 - Date created - 1999-11-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Challenges of thalidomide distribution in a hospital setting. AN - 70826458; 10512502 AB - The various physician, patient, and pharmacy requirements for participation in the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program and procedures that institutions may implement in order to comply with these requirements are described. In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). Because of the drug's known teratogenic effects, FDA tightly controls the distribution of thalidomide in the United States. To comply with FDA requirements, Celgene developed the S.T.E.P.S. oversight program, which includes registration of thalidomide prescribers and pharmacies that dispense thalidomide, extensive patient education about the risks associated with thalidomide, and a registry of all patients receiving thalidomide. The S.T.E.P.S. program is considered part of the product label. The pharmacy requirements of the program were developed with a focus on a retail pharmacy practice model, which does not adequately reflect current hospital practice. The pharmacy department of the National Institutes of Health Clinical Center developed a model that adapts the S.T.E.P.S. program requirements to inpatient and outpatient institutional pharmacy practice. Procedures for registering patients and prescribers and dispensing thalidomide in the hospital setting were developed; the procedures were designed to meet the needs of both the inpatient and outpatient pharmacies and to comply with the requirements of the S.T.E.P.S. program. JF - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists AU - Keravich, D P AU - Daniels, C E AD - Pharmacy Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 1721 EP - 1725 VL - 56 IS - 17 SN - 1079-2082, 1079-2082 KW - Anti-Infective Agents KW - 0 KW - Teratogens KW - Thalidomide KW - 4Z8R6ORS6L KW - Index Medicus KW - AIDS/HIV KW - United States KW - Humans KW - Pharmacy Service, Hospital -- standards KW - Immune System Diseases -- drug therapy KW - United States Food and Drug Administration -- legislation & jurisprudence KW - Male KW - Female KW - Anti-Infective Agents -- therapeutic use KW - Erythema Nodosum -- drug therapy KW - Drug Prescriptions -- standards KW - Guidelines as Topic KW - Thalidomide -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70826458?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.atitle=Challenges+of+thalidomide+distribution+in+a+hospital+setting.&rft.au=Keravich%2C+D+P%3BDaniels%2C+C+E&rft.aulast=Keravich&rft.aufirst=D&rft.date=1999-09-01&rft.volume=56&rft.issue=17&rft.spage=1721&rft.isbn=&rft.btitle=&rft.title=American+journal+of+health-system+pharmacy+%3A+AJHP+%3A+official+journal+of+the+American+Society+of+Health-System+Pharmacists&rft.issn=10792082&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-10 N1 - Date created - 1999-11-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ocular thrombosis and retinal degeneration induced in female F344 rats by 2-butoxyethanol. AN - 70824075; 10523872 AB - 2-butoxyethanol, used extensively for domestic and industrial purposes, was tested in our experiments for its potential to cause damage to female rat ocular tissues. Female rats were previously found to be particularly sensitive to 2-butoxyethanol. A group of eight female F344 rats (2 - 3 months old) were exposed by gavage to 250 mg of 2-butoxyethanol/kg b.w. per day for 3 consecutive days and sacrificed 24 h after the last dose. Eight female rats received the dosing vehicle (water) and served as controls. At necropsy, petechial hemorrhages were noted on the sclera. Microscopic examination revealed treatment-related effects in the eyes, in addition to other known effects of BE exposure such as disseminated thrombosis and necrosis and infarction in various organs. The spectrum of histopathological changes noted in the eyes included hemorrhages localized in the posterior layers of the retina, leading to photoreceptor degeneration. Thrombi were identified in ciliary processes and limbal blood vessels. Histological changes suggestive of the retinal ischemic-infarctive process were also noted. Possible pathogenic mechanisms of 2-butoxyethanol-induced retinopathy are discussed. JF - Human & experimental toxicology AU - Nyska, A AU - Maronpot, R R AU - Ghanayem, B I AD - National Institute of Health, National Institute of Environmental Health Sciences (NIEHS), PO Box 12233, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 577 EP - 582 VL - 18 IS - 9 SN - 0960-3271, 0960-3271 KW - Ethylene Glycols KW - 0 KW - n-butoxyethanol KW - I0P9XEZ9WV KW - Index Medicus KW - Rats KW - Limbus Corneae -- blood supply KW - Animals KW - Rats, Inbred F344 KW - Retinal Hemorrhage -- pathology KW - Ciliary Body -- pathology KW - Disseminated Intravascular Coagulation -- pathology KW - Ciliary Body -- blood supply KW - Retinal Hemorrhage -- chemically induced KW - Limbus Corneae -- pathology KW - Female KW - Disseminated Intravascular Coagulation -- chemically induced KW - Thrombosis -- chemically induced KW - Photoreceptor Cells, Vertebrate -- pathology KW - Thrombosis -- pathology KW - Ethylene Glycols -- toxicity KW - Photoreceptor Cells, Vertebrate -- drug effects KW - Eye Diseases -- chemically induced KW - Eye Diseases -- pathology KW - Retinal Degeneration -- pathology KW - Retinal Degeneration -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70824075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=Ocular+thrombosis+and+retinal+degeneration+induced+in+female+F344+rats+by+2-butoxyethanol.&rft.au=Nyska%2C+A%3BMaronpot%2C+R+R%3BGhanayem%2C+B+I&rft.aulast=Nyska&rft.aufirst=A&rft.date=1999-09-01&rft.volume=18&rft.issue=9&rft.spage=577&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-09 N1 - Date created - 1999-12-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Resiniferatoxin-type phorboid vanilloids display capsaicin-like selectivity at native vanilloid receptors on rat DRG neurons and at the cloned vanilloid receptor VR1. AN - 70821831; 10510454 AB - 1 Although the cloned rat vanilloid receptor VR1 appears to account for both receptor binding and calcium uptake, the identification of vanilloids selective for one or the other response is of importance because these ligands may induce distinct patterns of biological activities. 2 Phorbol 12,13-didecanoate 20-homovanillate (PDDHV) evoked 45Ca(2+)-uptake by rat dorsal root ganglion neurons (expressing native vanilloid receptors) in culture with an EC50 of 70 nM but inhibited [3H]-resiniferatoxin (RTX) binding to rat dorsal root ganglion membranes with a much lower potency (Ki>10,000 nM). This difference in potencies represents a more than 100 fold selectivity for capsaicin-type pharmacology. 3 45Ca2+ influx by PDDHV was fully inhibited by the competitive vanilloid receptor antagonist capsazepine, consistent with the calcium uptake occurring via vanilloid receptors. 4 PDDHV induced calcium mobilization in CHO cells transfected with the cloned rat vanilloid receptor VR1 with an EC50 of 125 nM and inhibited [3H]-RTX binding to these cells with an estimated Ki of 10,000 nM. By contrast, PDDHV failed to evoke a measurable calcium response in non-transfected CHO cells, confirming its action through VR1. 5 We conclude that PDDHV is two orders of magnitude more potent for inducing calcium uptake than for inhibiting RTX binding at vanilloid receptors, making this novel vanilloid a ligand selective for capsaicin-type pharmacology. These results emphasize the importance of monitoring multiple endpoints for evaluation of vanilloid receptor structure-activity relations. Furthermore, PDDHV now provides a tool to explore the biological correlates of capsaicin-type vanilloid pharmacology. JF - British journal of pharmacology AU - Szallasi, A AU - Szabó, T AU - Bíró, T AU - Modarres, S AU - Blumberg, P M AU - Krause, J E AU - Cortright, D N AU - Appendino, G AD - National Cancer Institute, Bethesda, Maryland, USA. arpads@thalamus.wustl.edu Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 428 EP - 434 VL - 128 IS - 2 SN - 0007-1188, 0007-1188 KW - DNA, Complementary KW - 0 KW - Diterpenes KW - Fluorescent Dyes KW - Neurotoxins KW - Receptors, Drug KW - phorbol 12,13-didecanoate 20-homovanillate KW - resiniferatoxin KW - A5O6P1UL4I KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Rats KW - Calcium -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - DNA, Complementary -- genetics KW - CHO Cells KW - Cell Membrane -- metabolism KW - Female KW - DNA, Complementary -- biosynthesis KW - Cricetinae KW - Cloning, Molecular KW - Ganglia, Spinal -- cytology KW - Diterpenes -- pharmacology KW - Receptors, Drug -- genetics KW - Receptors, Drug -- drug effects KW - Neurotoxins -- pharmacology KW - Ganglia, Spinal -- drug effects KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70821831?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=Resiniferatoxin-type+phorboid+vanilloids+display+capsaicin-like+selectivity+at+native+vanilloid+receptors+on+rat+DRG+neurons+and+at+the+cloned+vanilloid+receptor+VR1.&rft.au=Szallasi%2C+A%3BSzab%C3%B3%2C+T%3BB%C3%ADr%C3%B3%2C+T%3BModarres%2C+S%3BBlumberg%2C+P+M%3BKrause%2C+J+E%3BCortright%2C+D+N%3BAppendino%2C+G&rft.aulast=Szallasi&rft.aufirst=A&rft.date=1999-09-01&rft.volume=128&rft.issue=2&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-04 N1 - Date created - 2000-01-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1997 Oct 23;389(6653):816-24 [9349813] J Neurosci Methods. 1997 Feb;71(2):191-8 [9128156] Neuroscience. 1998 May;84(2):569-81 [9539227] Neuron. 1998 Sep;21(3):531-43 [9768840] Pharmacol Rev. 1999 Jun;51(2):159-212 [10353985] Mol Pharmacol. 1999 Sep;56(3):581-7 [10462546] Cell. 1980 Apr;19(4):1025-32 [7379122] Neuroscience. 1987 Oct;23(1):275-89 [3683864] J Neurosci. 1988 Sep;8(9):3208-20 [3171675] Neuroscience. 1989;30(2):515-20 [2747924] Trends Pharmacol Sci. 1990 Aug;11(8):330-3 [2203194] Brain Res. 1990 Jul 30;524(1):106-11 [2400923] Brain Res. 1990 Jun 18;520(1-2):131-40 [2169951] Life Sci. 1990;47(16):1399-408 [2174484] J Pharmacol Exp Ther. 1992 Sep;262(3):883-8 [1527730] J Pharmacol Exp Ther. 1993 Aug;266(2):678-83 [8355200] Br J Anaesth. 1995 Aug;75(2):157-68 [7577249] J Neurophysiol. 1996 Apr;75(4):1503-14 [8727394] J Med Chem. 1996 Jul 19;39(15):2939-52 [8709128] J Med Chem. 1996 Aug 2;39(16):3123-31 [8759633] Brain Res Mol Brain Res. 1996 Jan;35(1-2):173-82 [8717353] Eur J Pharmacol. 1996 Mar 28;299(1-3):221-8 [8901026] Pain. 1996 Dec;68(2-3):195-208 [9121806] J Investig Dermatol Symp Proc. 1997 Aug;2(1):56-60 [9487017] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatotoxicity in cancer patients receiving erb-38, a recombinant immunotoxin that targets the erbB2 receptor. AN - 70797025; 10499598 AB - To exploit overexpression of erbB2 in human cancers, we constructed a single-chain immunotoxin (erb-38) that contains the Fv portion of monoclonal antibody e23 fused to a truncated form of Pseudomonas exotoxin A. In a Phase I study, five breast cancer patients and one esophageal cancer patient received three doses of erb-38 at 1.0 and 2.0 microg/kg. Hepatotoxicity was observed in all patients. Immunohistochemistry showed the presence of erbB2 on hepatocytes explaining the liver toxicity of erb-38. We suggest that targeting of tumors with antibodies to erbB2 armed with radioisotopes or other toxic agents may result in unexpected organ toxicities due to erbB2 on normal cells. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Pai-Scherf, L H AU - Villa, J AU - Pearson, D AU - Watson, T AU - Liu, E AU - Willingham, M C AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2311 EP - 2315 VL - 5 IS - 9 SN - 1078-0432, 1078-0432 KW - Antibodies, Monoclonal KW - 0 KW - Antibodies, Neoplasm KW - Bacterial Toxins KW - Exotoxins KW - Immunotoxins KW - Recombinant Proteins KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Aspartate Aminotransferases KW - EC 2.6.1.1 KW - Alanine Transaminase KW - EC 2.6.1.2 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Alanine Transaminase -- metabolism KW - Humans KW - Liver -- metabolism KW - Liver Diseases -- enzymology KW - Antibodies, Neoplasm -- biosynthesis KW - Liver Diseases -- metabolism KW - Antibodies, Monoclonal -- immunology KW - Antibodies, Monoclonal -- therapeutic use KW - Aspartate Aminotransferases -- metabolism KW - Antibodies, Monoclonal -- pharmacokinetics KW - Liver -- drug effects KW - Adult KW - Middle Aged KW - Antibodies, Monoclonal -- adverse effects KW - Male KW - Female KW - Immunotoxins -- pharmacokinetics KW - Breast Neoplasms -- drug therapy KW - Receptor, ErbB-2 -- metabolism KW - Chemical and Drug Induced Liver Injury KW - Immunotoxins -- adverse effects KW - Recombinant Proteins -- pharmacokinetics KW - Breast Neoplasms -- metabolism KW - Exotoxins -- adverse effects KW - Bacterial Toxins -- immunology KW - Exotoxins -- immunology KW - Exotoxins -- pharmacokinetics KW - Bacterial Toxins -- adverse effects KW - Esophageal Neoplasms -- metabolism KW - Immunotoxins -- immunology KW - Bacterial Toxins -- pharmacokinetics KW - Bacterial Toxins -- therapeutic use KW - Recombinant Proteins -- immunology KW - Recombinant Proteins -- adverse effects KW - Immunotoxins -- therapeutic use KW - Exotoxins -- therapeutic use KW - Recombinant Proteins -- therapeutic use KW - Esophageal Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70797025?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Hepatotoxicity+in+cancer+patients+receiving+erb-38%2C+a+recombinant+immunotoxin+that+targets+the+erbB2+receptor.&rft.au=Pai-Scherf%2C+L+H%3BVilla%2C+J%3BPearson%2C+D%3BWatson%2C+T%3BLiu%2C+E%3BWillingham%2C+M+C%3BPastan%2C+I&rft.aulast=Pai-Scherf&rft.aufirst=L&rft.date=1999-09-01&rft.volume=5&rft.issue=9&rft.spage=2311&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Phase I study of raltitrexed, an antifolate thymidylate synthase inhibitor, in adult patients with advanced solid tumors. AN - 70784044; 10499608 AB - The purpose of this study was to perform a Phase I trial of raltitrexed, a selective inhibitor of thymidylate synthase, and to determine the pharmacokinetic and toxicity profiles as a function of raltitrexed dose. Fifty patients with advanced solid tumors and good performance status were treated with raltitrexed as a 15-min i.v. infusion every 3 weeks, at doses escalating from 0.6 to 4.5 mg/m2. Asthenia, neutropenia, and hepatic toxicity were the most common dose-limiting toxicities in this largely pretreated patient population, but they occurred during the initial cycle in only one of nine patients treated with 4.0 mg/m2 and in two of nine patients treated with 4.5 mg/m2. Only 2 of 13 patients treated with 3.5 mg/m2 ultimately experienced unacceptable toxicity after three and seven cycles, compared with 42 and 56% of patients receiving 4.0 and 4.5 mg/m2 after medians of three and two cycles, respectively. The maximum raltitrexed plasma concentration and the area under the plasma concentration-time curve increased in proportion to dose. Raltitrexed clearance was independent of dose and was associated with the estimated creatinine clearance. Asthenia, neutropenia, and hepatic transaminitis were dose-related and tended to occur more frequently when patients received three or more cycles of therapy. A 3-week treatment interval was feasible in the majority of patients at all doses. Although 4.0 mg/m2 appeared to be a safe starting dose in this pretreated patient population, about half who received two or more courses ultimately experienced dose-limiting toxicity. A dose of 3.5 mg/m2 was well tolerated in most patients. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Grem, J L AU - Sorensen, J M AU - Cullen, E AU - Takimoto, C H AU - Steinberg, S M AU - Chen, A P AU - Hamilton, J M AU - Arbuck, S G AU - McAtee, N AU - Lawrence, D AU - Goldspiel, B AU - Johnston, P G AU - Allegra, C J AD - National Cancer Institute-Medicine Branch, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. jgrem@helix.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2381 EP - 2391 VL - 5 IS - 9 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - Folic Acid Antagonists KW - Quinazolines KW - Thiophenes KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - raltitrexed KW - FCB9EGG971 KW - Index Medicus KW - Thymidylate Synthase -- antagonists & inhibitors KW - Folic Acid Antagonists -- therapeutic use KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Folic Acid Antagonists -- adverse effects KW - Aged KW - Middle Aged KW - Folic Acid Antagonists -- pharmacokinetics KW - Male KW - Female KW - Quinazolines -- pharmacokinetics KW - Enzyme Inhibitors -- adverse effects KW - Neoplasms -- drug therapy KW - Thiophenes -- adverse effects KW - Enzyme Inhibitors -- therapeutic use KW - Antimetabolites, Antineoplastic -- adverse effects KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Thiophenes -- therapeutic use KW - Thiophenes -- pharmacokinetics KW - Quinazolines -- therapeutic use KW - Enzyme Inhibitors -- pharmacokinetics KW - Quinazolines -- adverse effects KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70784044?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+Phase+I+study+of+raltitrexed%2C+an+antifolate+thymidylate+synthase+inhibitor%2C+in+adult+patients+with+advanced+solid+tumors.&rft.au=Grem%2C+J+L%3BSorensen%2C+J+M%3BCullen%2C+E%3BTakimoto%2C+C+H%3BSteinberg%2C+S+M%3BChen%2C+A+P%3BHamilton%2C+J+M%3BArbuck%2C+S+G%3BMcAtee%2C+N%3BLawrence%2C+D%3BGoldspiel%2C+B%3BJohnston%2C+P+G%3BAllegra%2C+C+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1999-09-01&rft.volume=5&rft.issue=9&rft.spage=2381&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinogenicity and mutagenicity of heterocyclic amines in transgenic mouse models. AN - 70781833; 10503912 AB - Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein1 promoter-human TGFalpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing both the interaction of nuclear oncogenes and growth factors in tumorigenesis. In addition, these mice provide an experimental model to test how environmental chemicals might interact with the c-myc and TGFalpha transgenes during the neoplastic process. Treatment of the double transgenic mice with both genotoxic agents such as diethylnitrosamine and 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) as well as the tumor promoter phenobarbital greatly accelerated the neoplastic process. To investigate the role of mutagenesis in the carcinogenic process, 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) induced mutagenesis and hepatocarcinogenicity was examined in C57BL/lacZ (Muta Mice) and double transgenic c-myc/lacZ mice that carry the lacZ mutation reporter gene. The MelQx hepatocarcinogenicity was associated with an increase in in vivo mutagenicity as scored by mutations in the lacZ reporter gene. These results suggest that transgenic mouse models may provide important tools for testing both the carcinogenic potential of environmental chemicals and the interaction/cooperation of these compounds with specific genes during the neoplastic process. JF - Cancer letters AU - Thorgeirsson, S S AU - Ryu, D Y AU - Weidner, V AU - Snyderwine, E G AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. snorri_thorgeirsson@nih.gov Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 245 EP - 247 VL - 143 IS - 2 SN - 0304-3835, 0304-3835 KW - DNA, Complementary KW - 0 KW - Mutagens KW - Quinolines KW - Quinoxalines KW - Transforming Growth Factor alpha KW - 2-amino-3-methylimidazo(4,5-f)quinoline KW - 30GL3D3T0G KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - 77500-04-0 KW - Index Medicus KW - Animals KW - DNA, Complementary -- genetics KW - Mice KW - Mice, Transgenic KW - Quinolines -- toxicity KW - Mutagenesis -- drug effects KW - Transforming Growth Factor alpha -- genetics KW - Neoplasms, Experimental -- chemically induced KW - Genes, myc KW - Quinoxalines -- toxicity KW - Mutagens -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70781833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Carcinogenicity+and+mutagenicity+of+heterocyclic+amines+in+transgenic+mouse+models.&rft.au=Thorgeirsson%2C+S+S%3BRyu%2C+D+Y%3BWeidner%2C+V%3BSnyderwine%2C+E+G&rft.aulast=Thorgeirsson&rft.aufirst=S&rft.date=1999-09-01&rft.volume=143&rft.issue=2&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-12 N1 - Date created - 1999-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pharmacokinetically guided Phase II study of carboxyamido-triazole in androgen-independent prostate cancer. AN - 70779261; 10499600 AB - We conducted a Phase II clinical trial of the antiproliferative, antimetastatic, and antiangiogenic agent carboxyamido-triazole (CAI), using pharmacokinetic assessment to guide drug dosing. Fifteen patients who had stage D2 androgen-independent prostate cancer with soft tissue metastases were enrolled. Because CAI previously had been shown to decrease prostate-specific antigen secretion in vitro, this marker was not used to assess disease status. The dose of CAI used in this study was calculated so that plasma steady-state maximum concentrations between 2.0 and 5.0 microg/ml would be maintained. Following the initial dosage adjustment, 93% (14 of 15) of patients were within the predicted range. Fourteen of 15 patients were evaluable for response. All of the 14 evaluable patients demonstrated progressive disease at approximately 2 months. Twelve patients progressed by computed tomography and or bone scan at 2 months, whereas two patients demonstrated clinical progression at 1.5 and 2 months. One patient was removed from study at 6 weeks due to grade II peripheral neuropathy lasting >1 month. Although no clinical responses were noted, a 27.7% decrease in serum vascular endothelial growth factor concentration was observed. CAI does not possess clinical activity in patients with androgen-independent prostate cancer and soft tissue metastases. Pharmacokinetically guided dosing, although found to be feasible using a Bayesian approach, was not found to be of practical benefit. Although plasma CAI concentrations were maintained within the designated range, grade III toxicity requiring drug discontinuation was still observed. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Bauer, K S AU - Figg, W D AU - Hamilton, J M AU - Jones, E C AU - Premkumar, A AU - Steinberg, S M AU - Dyer, V AU - Linehan, W M AU - Pluda, J M AU - Reed, E AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2324 EP - 2329 VL - 5 IS - 9 SN - 1078-0432, 1078-0432 KW - Androgens KW - 0 KW - Angiogenesis Inhibitors KW - Antineoplastic Agents KW - Triazoles KW - carboxyamido-triazole KW - 99519-84-3 KW - Index Medicus KW - Angiogenesis Inhibitors -- therapeutic use KW - Humans KW - Angiogenesis Inhibitors -- pharmacokinetics KW - Aged KW - Middle Aged KW - Angiogenesis Inhibitors -- adverse effects KW - Male KW - Prostatic Neoplasms -- metabolism KW - Adenocarcinoma -- metabolism KW - Antineoplastic Agents -- pharmacokinetics KW - Neoplasms, Hormone-Dependent -- drug therapy KW - Prostatic Neoplasms -- drug therapy KW - Triazoles -- adverse effects KW - Triazoles -- pharmacokinetics KW - Antineoplastic Agents -- adverse effects KW - Androgens -- physiology KW - Neoplasms, Hormone-Dependent -- metabolism KW - Triazoles -- therapeutic use KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70779261?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+pharmacokinetically+guided+Phase+II+study+of+carboxyamido-triazole+in+androgen-independent+prostate+cancer.&rft.au=Bauer%2C+K+S%3BFigg%2C+W+D%3BHamilton%2C+J+M%3BJones%2C+E+C%3BPremkumar%2C+A%3BSteinberg%2C+S+M%3BDyer%2C+V%3BLinehan%2C+W+M%3BPluda%2C+J+M%3BReed%2C+E&rft.aulast=Bauer&rft.aufirst=K&rft.date=1999-09-01&rft.volume=5&rft.issue=9&rft.spage=2324&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma. AN - 70778096; 10499610 AB - We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Shapiro, J D AU - Harold, N AU - Takimoto, C AU - Hamilton, J M AU - Vaughn, D AU - Chen, A AU - Steinberg, S M AU - Liewehr, D AU - Allegra, C AU - Monahan, B AU - Lash, A AU - Grollman, F AU - Flemming, D AU - Behan, K AU - Johnston, P G AU - Haller, D AU - Quinn, M AU - Morrison, G AU - Grem, J L AD - Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Naval Medical Center, Bethesda, Maryland 20889, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2399 EP - 2408 VL - 5 IS - 9 SN - 1078-0432, 1078-0432 KW - Interferon-alpha KW - 0 KW - Recombinant Proteins KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Leucovorin KW - Q573I9DVLP KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Interferon-alpha -- administration & dosage KW - Humans KW - Leucovorin -- administration & dosage KW - Aged KW - Quality of Life KW - Pilot Projects KW - Fluorouracil -- administration & dosage KW - Granulocyte-Macrophage Colony-Stimulating Factor -- administration & dosage KW - Adult KW - Middle Aged KW - Thymidylate Synthase -- metabolism KW - Female KW - Male KW - Adenocarcinoma -- enzymology KW - Gastrointestinal Neoplasms -- enzymology KW - Gastrointestinal Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Adenocarcinoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70778096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+pilot+study+of+interferon+alpha-2a%2C+fluorouracil%2C+and+leucovorin+given+with+granulocyte-macrophage+colony+stimulating+factor+in+advanced+gastrointestinal+adenocarcinoma.&rft.au=Shapiro%2C+J+D%3BHarold%2C+N%3BTakimoto%2C+C%3BHamilton%2C+J+M%3BVaughn%2C+D%3BChen%2C+A%3BSteinberg%2C+S+M%3BLiewehr%2C+D%3BAllegra%2C+C%3BMonahan%2C+B%3BLash%2C+A%3BGrollman%2C+F%3BFlemming%2C+D%3BBehan%2C+K%3BJohnston%2C+P+G%3BHaller%2C+D%3BQuinn%2C+M%3BMorrison%2C+G%3BGrem%2C+J+L&rft.aulast=Shapiro&rft.aufirst=J&rft.date=1999-09-01&rft.volume=5&rft.issue=9&rft.spage=2399&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Phase II study of high-dose tamoxifen in patients with hormone-refractory prostate cancer. AN - 70777720; 10499606 AB - Micromolar concentrations of tamoxifen inhibit the activity of protein kinase C and were recently shown to inhibit prostate cancer cell growth in preclinical studies. Because micromolar concentrations can be attained with high-dose therapy, the clinical activity of high-dose tamoxifen was evaluated in patients with metastatic adenocarcinoma of the prostate. Between December 1993 and February 1997, 30 patients with hormone-refractory metastatic adenocarcinoma of the prostate were continuously administered tamoxifen at 160 mg/m2/day. Therapy was continued until disease progression. All study patients had failed prior treatment with combined androgen blockade, had castrate levels of testosterone, and were heavily pretreated, having received a median of three prior regimens. The average steady-state plasma concentration of tamoxifen was 2.96+/-1.32 microM (mean +/- SD). Grade 3 neurotoxicity was observed in 29% of patients and was rapidly reversible and readily managed with dose modification. Otherwise, grade 3 toxicities were rare. One partial response (80% decline in prostate-specific antigen) was observed (3.3%), whereas disease stabilization was observed in six patients (20%), for a combined partial response/stable disease response rate of 23%. Median time to progression was 2.1 months, and median survival time was 10.5 months. High-dose tamoxifen therapy was well tolerated and associated with micromolar concentrations of tamoxifen in human plasma, and it demonstrated activity, albeit limited, in a heavily pretreated patient cohort with hormone-refractory prostate cancer. These findings suggest that further investigation of the role of protein kinase C modulation in prostate cancer is warranted. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Bergan, R C AU - Reed, E AU - Myers, C E AU - Headlee, D AU - Brawley, O AU - Cho, H K AU - Figg, W D AU - Tompkins, A AU - Linehan, W M AU - Kohler, D AU - Steinberg, S M AU - Blagosklonny, M V AD - Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2366 EP - 2373 VL - 5 IS - 9 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Drug Administration Schedule KW - Dose-Response Relationship, Drug KW - Aged, 80 and over KW - Humans KW - Quality of Life KW - Aged KW - Middle Aged KW - Drug Resistance, Neoplasm KW - Male KW - Survival Analysis KW - Prostatic Neoplasms -- metabolism KW - Tamoxifen -- blood KW - Adenocarcinoma -- metabolism KW - Adenocarcinoma -- blood KW - Tamoxifen -- pharmacokinetics KW - Tamoxifen -- therapeutic use KW - Antineoplastic Agents, Hormonal -- pharmacokinetics KW - Prostatic Neoplasms -- drug therapy KW - Prostatic Neoplasms -- blood KW - Antineoplastic Agents, Hormonal -- blood KW - Tamoxifen -- adverse effects KW - Adenocarcinoma -- drug therapy KW - Antineoplastic Agents, Hormonal -- adverse effects KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70777720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=A+Phase+II+study+of+high-dose+tamoxifen+in+patients+with+hormone-refractory+prostate+cancer.&rft.au=Bergan%2C+R+C%3BReed%2C+E%3BMyers%2C+C+E%3BHeadlee%2C+D%3BBrawley%2C+O%3BCho%2C+H+K%3BFigg%2C+W+D%3BTompkins%2C+A%3BLinehan%2C+W+M%3BKohler%2C+D%3BSteinberg%2C+S+M%3BBlagosklonny%2C+M+V&rft.aulast=Bergan&rft.aufirst=R&rft.date=1999-09-01&rft.volume=5&rft.issue=9&rft.spage=2366&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-22 N1 - Date created - 1999-11-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP). AN - 70054754; 10493628 AB - Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic peritoneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface for the treatment of peritoneal tumors. This article summarizes the results of 18 patients with peritoneal mesothelioma treated with CHPP. From June 1993 through April 1998, 18 patients with primary peritoneal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgical exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at the National Cancer Institute. Seventeen of 18 patients had malignant peritoneal mesothelioma, 13 with associated ascites. One patient had a symptomatic, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patients who had a recurrence after a prolonged progression-free interval (>6 months) after CHPP underwent re-treatment. CHPP parameters included median cisplatin dose of 530 mg (range, 187-816), perfusate volume 6.0 liter (range, 4-9), flow 1.5 liter/min (range, 1-2), intraperitoneal temperature 41 degrees C (range, 38.7-43.2), and central temperature 38.6 degrees C (range, 36.8-39.7). Median follow-up after CHPP is 19 months (range, 2-56) with no operative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, line sepsis, and clostridium difficile colitis. The major treatment-related toxicity was systemic renal toxicity at doses above what was defined as the maximum tolerated dose of cisplatin. Nine of 10 patients had resolution of their ascites postoperatively. Three patients who developed recurrent ascites (27, 22, and 10 months after initial treatment) were re-treated and had resolution of their ascites with ongoing responses at 24, 6, and 4 months after the second perfusion. The median progression-free survival was 26 months, and the overall 2-year survival was 80%. The median overall survival has not been reached. CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the abdomen and long-term survival, compared with historical controls, can be achieved with aggressive surgical debulking and CHPP. Re-treatment after initial response can result in a second long-term response. JF - Annals of surgical oncology AU - Park, B J AU - Alexander, H R AU - Libutti, S K AU - Wu, P AU - Royalty, D AU - Kranda, K C AU - Bartlett, D L AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 582 EP - 590 VL - 6 IS - 6 SN - 1068-9265, 1068-9265 KW - Antineoplastic Agents KW - 0 KW - Tumor Necrosis Factor-alpha KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Disease-Free Survival KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Aged KW - Adult KW - Treatment Outcome KW - Follow-Up Studies KW - Middle Aged KW - Adolescent KW - Female KW - Male KW - Survival Analysis KW - Mesothelioma -- drug therapy KW - Antineoplastic Agents -- administration & dosage KW - Mesothelioma -- surgery KW - Chemotherapy, Cancer, Regional Perfusion KW - Mesothelioma -- mortality KW - Peritoneal Neoplasms -- surgery KW - Peritoneal Neoplasms -- drug therapy KW - Peritoneal Neoplasms -- mortality KW - Cisplatin -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70054754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Treatment+of+primary+peritoneal+mesothelioma+by+continuous+hyperthermic+peritoneal+perfusion+%28CHPP%29.&rft.au=Park%2C+B+J%3BAlexander%2C+H+R%3BLibutti%2C+S+K%3BWu%2C+P%3BRoyalty%2C+D%3BKranda%2C+K+C%3BBartlett%2C+D+L&rft.aulast=Park&rft.aufirst=B&rft.date=1999-09-01&rft.volume=6&rft.issue=6&rft.spage=582&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-09 N1 - Date created - 1999-11-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Extragonadal teratocarcinoma in chimeric mice. AN - 70050937; 10490215 AB - Chimeric mice often are created through the genetic manipulation of the mouse embryo in the process of developing animal models of disease. These mice have variable percentages of their somatic and germ cells derived from the donor embryonic stem cells and host blastocysts. In the development of mouse models deficient in the breast cancer susceptibility gene 2 (Brca2) or the 70-kd heat shock protein (Hsp70-2), 3-4-week-old chimeras developed single or multiple masses composed of both well-differentiated and poorly differentiated tissues derived from all three germ layers. These cases of extragonadal teratocarcinoma, a rarely reported tumor, may be related to the genetic predisposition of the 129/Ola mouse strain used to generate the embryonic stem cells. JF - Veterinary pathology AU - Blackshear, P AU - Mahler, J AU - Bennett, L M AU - McAllister, K A AU - Forsythe, D AU - Davis, B J AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 457 EP - 460 VL - 36 IS - 5 SN - 0300-9858, 0300-9858 KW - BRCA2 Protein KW - 0 KW - HSP70 Heat-Shock Proteins KW - Neoplasm Proteins KW - Transcription Factors KW - Index Medicus KW - HSP70 Heat-Shock Proteins -- genetics KW - Animals KW - Testis -- pathology KW - Neoplasm Proteins -- genetics KW - Mice, Inbred C57BL KW - Disease Models, Animal KW - Mice KW - Transcription Factors -- genetics KW - Male KW - Teratocarcinoma -- veterinary KW - Genital Neoplasms, Male -- pathology KW - Chimera KW - Genital Neoplasms, Male -- veterinary KW - Rodent Diseases -- pathology KW - Rodent Diseases -- genetics KW - Genital Neoplasms, Male -- genetics KW - Teratocarcinoma -- pathology KW - Teratocarcinoma -- genetics KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70050937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Veterinary+pathology&rft.atitle=Extragonadal+teratocarcinoma+in+chimeric+mice.&rft.au=Blackshear%2C+P%3BMahler%2C+J%3BBennett%2C+L+M%3BMcAllister%2C+K+A%3BForsythe%2C+D%3BDavis%2C+B+J&rft.aulast=Blackshear&rft.aufirst=P&rft.date=1999-09-01&rft.volume=36&rft.issue=5&rft.spage=457&rft.isbn=&rft.btitle=&rft.title=Veterinary+pathology&rft.issn=03009858&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Management of extremity recurrences after complete responses to isolated limb perfusion in patients with melanoma. AN - 70050334; 10493624 AB - Despite high rates of complete responses (CRs) to isolated limb perfusion (ILP) for patients with in-transit melanoma (60% to 90%), extremity recurrences are common. We evaluated our experience with managing these recurrences to determine how best to treat these patients. Between April 1992 and April 1998, 72 patients experienced CRs after hyperthermic ILP using Melphalan, with (n = 46) or without (n = 26) tumor necrosis factor. Of these, 25 patients (35%) experienced initial recurrences in the extremities, and they form the basis of this study. Three patients who underwent repeat ILP for treatment of their recurrences experienced a second CR and recurrence in the extremity (at 9, 15, and 16 months), allowing analysis of 28 cases. For 5 of 20 recurrences managed with excision, 2 of 6 managed with repeat ILP, and 0 of 2 managed with systemic treatment, the patient was free of disease at the last follow-up examination (median follow-up period, 11 months). Isolated extremity recurrences after CRs to ILP occurred in 35% of patients. Initially, these could be managed successfully by excision or repeat ILP for the majority of patients (92%). We recommend excision of small-volume recurrent disease, reserving repeat ILP for patients with increasing numbers of lesions or increasing rapidity of in-field recurrences. JF - Annals of surgical oncology AU - Feldman, A L AU - Alexander, H R AU - Bartlett, D L AU - Fraker, D L AU - Libutti, S K AD - Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 562 EP - 567 VL - 6 IS - 6 SN - 1068-9265, 1068-9265 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Tumor Necrosis Factor-alpha KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Disease-Free Survival KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Humans KW - Aged KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Extremities KW - Aged, 80 and over KW - Melphalan -- administration & dosage KW - Adult KW - Middle Aged KW - Retreatment KW - Female KW - Male KW - Melanoma -- pathology KW - Neoplasm Recurrence, Local -- drug therapy KW - Chemotherapy, Cancer, Regional Perfusion KW - Melanoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70050334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Management+of+extremity+recurrences+after+complete+responses+to+isolated+limb+perfusion+in+patients+with+melanoma.&rft.au=Feldman%2C+A+L%3BAlexander%2C+H+R%3BBartlett%2C+D+L%3BFraker%2C+D+L%3BLibutti%2C+S+K&rft.aulast=Feldman&rft.aufirst=A&rft.date=1999-09-01&rft.volume=6&rft.issue=6&rft.spage=562&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-09 N1 - Date created - 1999-11-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Ann Surg Oncol. 1999 Sep;6(6):524 [10493618] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of open label pulse cyclophosphamide therapy on MRI measures of disease activity in five patients with refractory relapsing-remitting multiple sclerosis. AN - 70047839; 10496187 AB - To evaluate the response to cyclophosphamide (CTX) of five patients who failed an average three treatments with multiple other therapeutic agents, using serial monthly MRI measures. Five patients with relapsing-remitting multiple sclerosis (MS) and documented MRI disease activity were started on monthly pulse intravenous CTX at a dose of 1 g/m2. CTX was administered without an induction phase according to the protocol similar to the treatment of lupus nephritis. The five patients were followed with monthly MRI and clinical evaluation for a mean of 28 months. All the patients showed a rapid reduction in the contrast-enhancing lesion frequency and in three patients there was a decrease in the T2 lesion load within the first 5 months after starting CTX treatment. The administration of CTX during overnight hospitalization was safe and well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some rapidly deteriorating refractory patients and further controlled study should be considered in order to full evaluate this type of treatment as a potential therapy in MS. JF - Journal of neuroimmunology AU - Gobbini, M I AU - Smith, M E AU - Richert, N D AU - Frank, J A AU - McFarland, H F AD - Neuroimmunology Branch of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 142 EP - 149 VL - 99 IS - 1 SN - 0165-5728, 0165-5728 KW - Immunosuppressive Agents KW - 0 KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Drug Evaluation KW - Drug Administration Schedule KW - Injections, Intravenous KW - Humans KW - Adult KW - Treatment Outcome KW - Disease Progression KW - Pilot Projects KW - Middle Aged KW - Male KW - Female KW - Magnetic Resonance Imaging KW - Cyclophosphamide -- administration & dosage KW - Cyclophosphamide -- therapeutic use KW - Brain -- pathology KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- drug therapy KW - Multiple Sclerosis -- drug therapy KW - Multiple Sclerosis -- pathology KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70047839?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroimmunology&rft.atitle=Effect+of+open+label+pulse+cyclophosphamide+therapy+on+MRI+measures+of+disease+activity+in+five+patients+with+refractory+relapsing-remitting+multiple+sclerosis.&rft.au=Gobbini%2C+M+I%3BSmith%2C+M+E%3BRichert%2C+N+D%3BFrank%2C+J+A%3BMcFarland%2C+H+F&rft.aulast=Gobbini&rft.aufirst=M&rft.date=1999-09-01&rft.volume=99&rft.issue=1&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroimmunology&rft.issn=01655728&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-04 N1 - Date created - 1999-10-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of the p63/p73L/p51/p40/CUSP/KET gene in human cancer cell lines using intronic primers. AN - 70041387; 10485447 AB - After the identification of p73, a second homologue of the human p53 tumor suppressor gene has been reported and named p63/p73L/p51/p40/CUSP/KET. We have investigated the hypotheses that: (a) p63 is mutated in diverse types of human cancers; and (b) p63 functions in the same pathway as p53 and p73 in the process of carcinogenesis; therefore, mutations in these three genes would be mutually exclusive. We have analyzed the genomic structure of the p63 gene and have performed mutational analyses on 54 human cell lines using intronic primers flanking each exon. We have confirmed that the human p63 open reading frame encodes the same length of protein as murine p63 that was initially reported to be 39 amino acids longer than human p63. By mutational analysis, we have shown that DLD1 and SKOV3 cells have either heterozygous mutations or polymorphisms in the putative DNA binding domain of p63. In these cell lines, p63 is biallelically expressed. We conclude that mutations in the p63 gene are rare in human cell lines. The fact that DLD1 is abnormal for both p63 and p53 genes suggests that they may not be involved in the same tumor suppressor pathway. JF - Cancer research AU - Hagiwara, K AU - McMenamin, M G AU - Miura, K AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 4165 EP - 4169 VL - 59 IS - 17 SN - 0008-5472, 0008-5472 KW - CKAP4 protein, human KW - 0 KW - DNA-Binding Proteins KW - Membrane Proteins KW - Phosphoproteins KW - TP63 protein, human KW - Trans-Activators KW - Transcription Factors KW - Tumor Suppressor Proteins KW - Index Medicus KW - Base Sequence KW - Tumor Cells, Cultured KW - Genes, p53 KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Phosphoproteins -- genetics KW - Genes, Tumor Suppressor KW - Introns KW - Mutation KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70041387?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Mutational+analysis+of+the+p63%2Fp73L%2Fp51%2Fp40%2FCUSP%2FKET+gene+in+human+cancer+cell+lines+using+intronic+primers.&rft.au=Hagiwara%2C+K%3BMcMenamin%2C+M+G%3BMiura%2C+K%3BHarris%2C+C+C&rft.aulast=Hagiwara&rft.aufirst=K&rft.date=1999-09-01&rft.volume=59&rft.issue=17&rft.spage=4165&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF091627; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship between a GABAA alpha 6 Pro385Ser substitution and benzodiazepine sensitivity. AN - 70037592; 10484961 AB - In humans, interindividual variation in sensitivity to benzodiazepine drugs may correlate with behavioral variation, including vulnerability to disease states such as alcoholism. In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABAA alpha 6 receptor. The authors detected a Pro385Ser [1236C > T] amino acid substitution in the human GABAA alpha 6 that may influence alcohol sensitivity. In this pilot study, they evaluated the contribution of this polymorphism to benzodiazepine sensitivity. Sensitivity to diazepam was assessed in 51 children of alcoholics by using two eye movement measures: peak saccadic velocity and average smooth pursuit gain. Association analysis was performed with saccadic velocity and smooth pursuit gain as dependent variables and comparing Pro385/Ser385 heterozygotes and Pro385/Pro385 homozygotes. The Pro385Ser genotype was associated with less diazepam-induced impairment of saccadic velocity but not with smooth pursuit gain. The Pro385Ser genotype may play a role in benzodiazepine sensitivity and conditions, such as alcoholism, that may be correlated with this trait. JF - The American journal of psychiatry AU - Iwata, N AU - Cowley, D S AU - Radel, M AU - Roy-Byrne, P P AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md., USA. nakao@fujita-hu.ac.jp Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1447 EP - 1449 VL - 156 IS - 9 SN - 0002-953X, 0002-953X KW - Anti-Anxiety Agents KW - 0 KW - Receptors, GABA-A KW - Benzodiazepines KW - 12794-10-4 KW - Ethanol KW - 3K9958V90M KW - Serine KW - 452VLY9402 KW - Proline KW - 9DLQ4CIU6V KW - Diazepam KW - Q3JTX2Q7TU KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Homozygote KW - Polymorphism, Genetic KW - Ethanol -- pharmacology KW - Humans KW - Diazepam -- pharmacology KW - Pilot Projects KW - Alcoholism -- genetics KW - Pursuit, Smooth -- genetics KW - Pursuit, Smooth -- drug effects KW - Child of Impaired Parents KW - Pharmacogenetics KW - Serine -- genetics KW - Rats KW - Proline -- genetics KW - Genotype KW - Anti-Anxiety Agents -- pharmacology KW - Heterozygote KW - Adult KW - Saccades -- genetics KW - Adolescent KW - Saccades -- drug effects KW - Male KW - Female KW - Receptors, GABA-A -- genetics KW - Amino Acid Substitution -- genetics KW - Receptors, GABA-A -- drug effects KW - Benzodiazepines -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70037592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Relationship+between+a+GABAA+alpha+6+Pro385Ser+substitution+and+benzodiazepine+sensitivity.&rft.au=Iwata%2C+N%3BCowley%2C+D+S%3BRadel%2C+M%3BRoy-Byrne%2C+P+P%3BGoldman%2C+D&rft.aulast=Iwata&rft.aufirst=N&rft.date=1999-09-01&rft.volume=156&rft.issue=9&rft.spage=1447&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-27 N1 - Date created - 1999-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Well-done, grilled red meat increases the risk of colorectal adenomas. AN - 70032643; 10485479 AB - Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer. A case-control study of colorectal adenomas was conducted at the National Naval Medical Center (Bethesda, MD) between April 1994 and September 1996. All cases (n = 146) were diagnosed with colorectal adenomas at sigmoidoscopy or colonoscopy and histologically confirmed. Controls (n = 228) were screened with sigmoidoscopy and found not to have colorectal adenomas. The subjects completed a food frequency questionnaire and answered detailed questions on meat-cooking practices. We used frequency and portion size to estimate grams of meat consumed per day for total meat as well as for meat subgroups defined by cooking methods and doneness levels. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, total caloric intake, reason for screening (routine or other), and several established risk factors for colorectal adenomas or cancer, including the use of nonsteroidal anti-inflammatory drugs, physical activity, and pack-years of cigarette smoking. There was an increased risk of 11% per 10 g/day (or 2.5 oz/week) of reported red meat consumption (OR, 1.11; CI, 1.03-1.19). The increased risk was mainly associated with well-done/very well-done red meat, with an excess risk of 29% per 10 g/day (OR, 1.29; CI, 1.08-1.54) versus an excess of 10% per 10 g/day (OR, 1.10; CI, 0.96-1.26) for consumption of rare/medium red meat. High-temperature cooking methods were also associated with increased risk; 26% per 10 g/day (OR, 1.26; CI, 1.06-1.50) of grilled red meat and 15% per 10 g/day (OR, 1.15; CI, 0.97-1.36) of pan-fried red meat consumption. There was an increased risk of colorectal adenomas associated with higher intake of red meat, most of which was due to the subgroup of red meat that was cooked until well done/very well done and/or by high-temperature cooking techniques, such as grilling. These results are consistent with the hypothesis that carcinogenic compounds formed by high-temperature cooking techniques, such as heterocyclic amines and polycyclic aromatic hydrocarbons, may contribute to the risk of developing colorectal tumors. JF - Cancer research AU - Sinha, R AU - Chow, W H AU - Kulldorff, M AU - Denobile, J AU - Butler, J AU - Garcia-Closas, M AU - Weil, R AU - Hoover, R N AU - Rothman, N AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, Maryland 20892, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 4320 EP - 4324 VL - 59 IS - 17 SN - 0008-5472, 0008-5472 KW - Index Medicus KW - Risk Factors KW - Humans KW - Cooking KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Meat KW - Colorectal Neoplasms -- etiology KW - Adenoma -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70032643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Well-done%2C+grilled+red+meat+increases+the+risk+of+colorectal+adenomas.&rft.au=Sinha%2C+R%3BChow%2C+W+H%3BKulldorff%2C+M%3BDenobile%2C+J%3BButler%2C+J%3BGarcia-Closas%2C+M%3BWeil%2C+R%3BHoover%2C+R+N%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1999-09-01&rft.volume=59&rft.issue=17&rft.spage=4320&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A plethora of lesion-replicating DNA polymerases. AN - 70031552; 10485842 JF - Genes & development AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2725 USA. woodgate@helix.nih.gov Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 2191 EP - 2195 VL - 13 IS - 17 SN - 0890-9369, 0890-9369 KW - Bacterial Proteins KW - 0 KW - DinB protein, E coli KW - Escherichia coli Proteins KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA polymerase iota KW - EC 2.7.7.- KW - Nucleotidyltransferases KW - REV1 protein, S cerevisiae KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- metabolism KW - Humans KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - DNA-Directed DNA Polymerase -- metabolism KW - DNA Repair KW - DNA Damage KW - DNA Replication UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70031552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=A+plethora+of+lesion-replicating+DNA+polymerases.&rft.au=Woodgate%2C+R&rft.aulast=Woodgate&rft.aufirst=R&rft.date=1999-09-01&rft.volume=13&rft.issue=17&rft.spage=2191&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-12 N1 - Date created - 1999-10-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of experimental melanin protein-induced uveitis (EMIU) by targeting nitric oxide via phosphatidylcholine-specific phospholipase C. AN - 70027809; 10479388 AB - Experimental melanin protein-induced uveitis (EMIU) is an autoimmune uveitis induced by immunization with uveal melanin protein. Fas and FasL enhancement is reported in rats with EMIU. Tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C, inhibits inducible nitric oxide synthase (iNOS) induction. In two independent experiments, 35 Lewis rats with EMIU received either D609 or PBS daily. The eyes and draining lymph nodes were collected for histology, analyses of nitrite, peroxide, and superoxide dismutase, Fas and FasL immunochemistry, in situ hybridization for iNOS mRNA and in situ apoptosis detection at the peak of the disease. Both experiments showed significant inhibition of EMIU by D609. Decreases in nitrite and peroxide, increase of superoxide dismutase and lower expressions of iNOS mRNA were found in D609-treated, as compared to PBS-treated eyes. There was mild enhancement of Fas and FasL in the eyes and lymph nodes of D609-injected animals. DNA fragmentation was increased in the lymph nodes of D609-treated rats. We conclude that iNOS activation is responsible for NO production in eyes with EMIU. The suppressive effect of D609 on EMIU may result from scavenging NO and activating apoptosis previously inhibited by NO along with other anti-inflammatory effects. Copyright 1999 Academic Press. JF - Journal of autoimmunity AU - Matteson, D M AU - Shen, D F AU - Chan, C C AD - National Eye Institute, Bethesda, Maryland 20892-1857, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 197 EP - 204 VL - 13 IS - 2 SN - 0896-8411, 0896-8411 KW - Bridged-Ring Compounds KW - 0 KW - Eye Proteins KW - Fas Ligand Protein KW - Melanins KW - Membrane Glycoproteins KW - Thiones KW - Tnfsf6 protein, rat KW - Nitric Oxide KW - 31C4KY9ESH KW - tricyclodecane-9-yl-xanthogenate KW - 83373-60-8 KW - Nitric Oxide Synthase KW - EC 1.14.13.39 KW - Nitric Oxide Synthase Type II KW - Nos2 protein, rat KW - Type C Phospholipases KW - EC 3.1.4.- KW - phosphatidylcholine-specific phospholipase C KW - EC 3.1.4.3 KW - Index Medicus KW - Animals KW - Uvea -- pathology KW - Rats, Inbred Lew KW - Melanins -- immunology KW - Rats KW - Down-Regulation KW - Enzyme Induction -- drug effects KW - Eye Proteins -- immunology KW - Apoptosis -- drug effects KW - Female KW - Membrane Glycoproteins -- isolation & purification KW - Type C Phospholipases -- antagonists & inhibitors KW - Thiones -- therapeutic use KW - Autoimmune Diseases -- etiology KW - Autoimmune Diseases -- drug therapy KW - Nitric Oxide -- metabolism KW - Autoimmune Diseases -- chemically induced KW - Uveitis -- immunology KW - Bridged-Ring Compounds -- therapeutic use KW - Uveitis -- etiology KW - Uveitis -- drug therapy KW - Uveitis -- chemically induced KW - Nitric Oxide Synthase -- biosynthesis KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70027809?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+autoimmunity&rft.atitle=Inhibition+of+experimental+melanin+protein-induced+uveitis+%28EMIU%29+by+targeting+nitric+oxide+via+phosphatidylcholine-specific+phospholipase+C.&rft.au=Matteson%2C+D+M%3BShen%2C+D+F%3BChan%2C+C+C&rft.aulast=Matteson&rft.aufirst=D&rft.date=1999-09-01&rft.volume=13&rft.issue=2&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Journal+of+autoimmunity&rft.issn=08968411&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-19 N1 - Date created - 2000-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuropsychiatric toxicity associated with cytokine therapies. AN - 70026722; 10479948 AB - The cytokines interleukin-2 and interferon-alpha are potent biological agents used to treat malignancy, infectious diseases, and neurodegenerative disorders. While these medications show substantial therapeutic promise, the neuropsychiatric toxicity associated with these agents is often treatment-limiting. The pathophysiology of this toxicity is not well delineated, and adverse effects to the central nervous system are often misdiagnosed by clinicians. This report reviews the preclinical and clinical literature describing the morbidity associated with these agents and suggests appropriate clinical management strategies and future directions for research. JF - Psychosomatics AU - Lerner, D M AU - Stoudemire, A AU - Rosenstein, D L AD - Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD 20892-1274, USA. PY - 1999 SP - 428 EP - 435 VL - 40 IS - 5 SN - 0033-3182, 0033-3182 KW - Antineoplastic Agents KW - 0 KW - Antiviral Agents KW - Cytokines KW - Psychotropic Drugs KW - Index Medicus KW - Endocrine System Diseases -- psychology KW - Humans KW - Endocrine System Diseases -- chemically induced KW - Psychotropic Drugs -- therapeutic use KW - Cytokines -- adverse effects KW - Mental Disorders -- drug therapy KW - Mental Disorders -- chemically induced KW - Brain -- pathology KW - Brain -- drug effects KW - Antiviral Agents -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70026722?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychosomatics&rft.atitle=Neuropsychiatric+toxicity+associated+with+cytokine+therapies.&rft.au=Lerner%2C+D+M%3BStoudemire%2C+A%3BRosenstein%2C+D+L&rft.aulast=Lerner&rft.aufirst=D&rft.date=1999-09-01&rft.volume=40&rft.issue=5&rft.spage=428&rft.isbn=&rft.btitle=&rft.title=Psychosomatics&rft.issn=00333182&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-15 N1 - Date created - 1999-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A type 2 diabetes-associated polymorphic ARE motif affecting expression of PPP1R3 is involved in RNA-protein interactions. AN - 70025143; 10479482 AB - We have previously described a polymorphism in the 3' untranslated region (UTR) of the PPP1R3 gene that encodes the muscle-specific glycogen-targeting regulatory PP1 subunit. This polymorphism alters the distance between two putative mRNA-destabilizing ATTTA (AUUUA) motifs and is distinguished by a 10-nucleotide (allele ARE1) vs a 2-nucleotide interval (allele ARE2). ARE2 is associated with insulin resistance as well as increased prevalence of type 2 diabetes in the Pima Indians, and correlates with reduced expression of this subunit in vivo, causing a 10-fold half-life reduction of reporter mRNA in NIH3T3 cells. Gel shift assays, Northwestern blotting, and RNA-protein UV crosslinking revealed three proteins (43, 80, and 139 kDa) binding to the polymorphic ARE region in these cells. The interactions are sequence specific, and can be suppressed by an unlabeled competitor in a dose-dependent manner. The less stable ARE2 allele shows at least 2-fold higher relative protein binding, indicating that the polymorphic ARE region has a mRNA-destabilizing role. We suggest that the increased protein binding to ARE2 contributes to a faster degradation of PPP1R3 mRNA carrying this allele, and the resulting lower concentration of the protein contributes to insulin resistance, thus increasing the risk for development of type 2 diabetes. JF - Molecular genetics and metabolism AU - Xia, J AU - Bogardus, C AU - Prochazka, M AD - Phoenix Epidemiology and Clinical Research Branch, National Institutes of Health, Phoenix, Arizona 85016, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 48 EP - 55 VL - 68 IS - 1 SN - 1096-7192, 1096-7192 KW - 3' Untranslated Regions KW - 0 KW - RNA Probes KW - RNA, Messenger KW - RNA-Binding Proteins KW - PPP1R3A protein, human KW - EC 3.1.3.- KW - Phosphoprotein Phosphatases KW - EC 3.1.3.16 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Polymorphism, Genetic KW - Humans KW - Mice KW - Protein Binding KW - Mutagenesis, Site-Directed KW - Regulatory Sequences, Nucleic Acid KW - Cells, Cultured KW - Cytoplasm -- metabolism KW - Gene Expression Regulation KW - Binding Sites -- genetics KW - Diabetes Mellitus, Type 2 -- enzymology KW - RNA-Binding Proteins -- metabolism KW - RNA, Messenger -- metabolism KW - Phosphoprotein Phosphatases -- metabolism KW - Phosphoprotein Phosphatases -- genetics KW - Diabetes Mellitus, Type 2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025143?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+genetics+and+metabolism&rft.atitle=A+type+2+diabetes-associated+polymorphic+ARE+motif+affecting+expression+of+PPP1R3+is+involved+in+RNA-protein+interactions.&rft.au=Xia%2C+J%3BBogardus%2C+C%3BProchazka%2C+M&rft.aulast=Xia&rft.aufirst=J&rft.date=1999-09-01&rft.volume=68&rft.issue=1&rft.spage=48&rft.isbn=&rft.btitle=&rft.title=Molecular+genetics+and+metabolism&rft.issn=10967192&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. AN - 70019464; 10476001 AB - Three cases of heparin-induced thrombocytopenia (HIT) are reported that were provoked by daily heparin flushes of central venous access devices. Each case had confounding features that delayed recognition of the problem. A review of the literature revealed only 29 previously reported cases of HIT secondary to heparin flushes. However, the true incidence of this problem is unknown. A high index of suspicion and confirmatory laboratory tests are necessary to make the diagnosis. JF - Journal of internal medicine AU - Kadidal, V V AU - Mayo, D J AU - Horne, M K AD - Hematology Service, Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 325 EP - 329 VL - 246 IS - 3 SN - 0954-6820, 0954-6820 KW - Anticoagulants KW - 0 KW - Heparin KW - 9005-49-6 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Female KW - Platelet Count KW - Catheterization, Central Venous KW - Anticoagulants -- adverse effects KW - Thrombocytopenia -- chemically induced KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70019464?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+internal+medicine&rft.atitle=Heparin-induced+thrombocytopenia+%28HIT%29+due+to+heparin+flushes%3A+a+report+of+three+cases.&rft.au=Kadidal%2C+V+V%3BMayo%2C+D+J%3BHorne%2C+M+K&rft.aulast=Kadidal&rft.aufirst=V&rft.date=1999-09-01&rft.volume=246&rft.issue=3&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Journal+of+internal+medicine&rft.issn=09546820&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-20 N1 - Date created - 1999-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). AN - 70015737; 10469617 AB - Prostate cancer is the most common malignancy in males and is the second most common cause of cancer mortality in American men. Polymorphisms have been identified in two genes, the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5-reductase type II gene (SRD5A2) that are involved with androgen biosynthesis and metabolism. The CYP17 A2 allele contains a T-->C transition in the 5' promoter region that creates an additional Sp1-type (CCACC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels. We tested genotypes in 108 prostate cases and 167 controls along with samples (n = 340) from several different ethnic groups. The CYP17 A2 allele (combined A1/A2 and A2/A2 genotypes) occurred at a higher frequency in Caucasian patients with prostate cancer (70%) than in Caucasian clinical control urology patients (57%), suggesting that the A2 allele may convey increased risk for prostate cancer [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.0-3.0]. Blacks and Caucasians had a similar frequency of the A2 genotype (16 and 17%, respectively) while Taiwanese had the highest frequency (27%). The SRD5A2 leucine genotype was most frequent in Taiwanese (28%), intermediate in Caucasians (8.5%) and lowest in Blacks (2.5%). Genotypes having a SRD5A2 leucine allele were somewhat more common in prostate cancer cases (56%) than in controls (49%) (OR = 1.4, 95% CI = 0.8-2.2) but this difference was not significant. These results support the hypothesis that some allelic variants of genes involved in androgen biosynthesis and metabolism may be associated with prostate cancer risk. JF - Carcinogenesis AU - Lunn, R M AU - Bell, D A AU - Mohler, J L AU - Taylor, J A AD - Laboratory of Computational Biology and Risk Assessment, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1727 EP - 1731 VL - 20 IS - 9 SN - 0143-3334, 0143-3334 KW - Isoenzymes KW - 0 KW - Dihydrotestosterone KW - 08J2K08A3Y KW - Testosterone KW - 3XMK78S47O KW - Steroid 17-alpha-Hydroxylase KW - EC 1.14.14.19 KW - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase KW - EC 1.3.99.5 KW - Index Medicus KW - Taiwan KW - Odds Ratio KW - Gene Frequency KW - Testosterone -- metabolism KW - Polymorphism, Genetic KW - Humans KW - North Carolina -- epidemiology KW - Asian Continental Ancestry Group -- genetics KW - European Continental Ancestry Group -- genetics KW - Genotype KW - Risk KW - African Continental Ancestry Group -- genetics KW - Case-Control Studies KW - Genetic Predisposition to Disease KW - Dihydrotestosterone -- metabolism KW - Male KW - Adenocarcinoma -- enzymology KW - Adenocarcinoma -- epidemiology KW - Neoplasms, Hormone-Dependent -- ethnology KW - Adenocarcinoma -- ethnology KW - Prostatic Neoplasms -- epidemiology KW - Neoplasms, Hormone-Dependent -- enzymology KW - Prostatic Neoplasms -- ethnology KW - Steroid 17-alpha-Hydroxylase -- genetics KW - Prostatic Neoplasms -- genetics KW - Prostatic Neoplasms -- enzymology KW - Adenocarcinoma -- genetics KW - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase -- genetics KW - Neoplasms, Hormone-Dependent -- genetics KW - Neoplasms, Hormone-Dependent -- epidemiology KW - Isoenzymes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70015737?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Prostate+cancer+risk+and+polymorphism+in+17+hydroxylase+%28CYP17%29+and+steroid+reductase+%28SRD5A2%29.&rft.au=Lunn%2C+R+M%3BBell%2C+D+A%3BMohler%2C+J+L%3BTaylor%2C+J+A&rft.aulast=Lunn&rft.aufirst=R&rft.date=1999-09-01&rft.volume=20&rft.issue=9&rft.spage=1727&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and safety of high-dose and extended-interval regimens of levofloxacin in human immunodeficiency virus-infected patients. AN - 70013512; 10471591 AB - The pharmacokinetics of levofloxacin, administered in high doses and with extended dosing intervals, was studied in human immunodeficiency virus (HIV)-infected patients. Thirty patients received either 750 mg of the drug or a placebo once daily for 14 days, followed by 750 mg or 1,000 mg of the drug or a placebo three times weekly for an additional 14 days. Levofloxacin disposition was characterized by rapid oral absorption, with peak concentrations occurring approximately 1.5 h after dosing and elimination half-lives from 7.2 to 9.4 h. The overall incidence of any adverse effect was 70% (1,000 mg) to 95% (750 mg) for levofloxacin-treated patients and 71% for those taking the placebo. Levofloxacin pharmacokinetic parameters for HIV-infected patients were consistent with those observed in studies of healthy volunteers. JF - Antimicrobial agents and chemotherapy AU - Piscitelli, S C AU - Spooner, K AU - Baird, B AU - Chow, A T AU - Fowler, C L AU - Williams, R R AU - Natarajan, J AU - Masur, H AU - Walker, R E AD - Departments of Pharmacy, National Institutes of Health, Bethesda, Maryland 20892-1880, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2323 EP - 2327 VL - 43 IS - 9 SN - 0066-4804, 0066-4804 KW - Anti-Infective Agents KW - 0 KW - Levofloxacin KW - 6GNT3Y5LMF KW - Ofloxacin KW - A4P49JAZ9H KW - Index Medicus KW - AIDS/HIV KW - Administration, Oral KW - Drug Administration Schedule KW - CD4 Lymphocyte Count -- drug effects KW - Half-Life KW - Double-Blind Method KW - Area Under Curve KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Intestinal Absorption KW - Male KW - Female KW - Ofloxacin -- administration & dosage KW - Anti-Infective Agents -- adverse effects KW - HIV Infections -- blood KW - Anti-Infective Agents -- pharmacokinetics KW - HIV Infections -- drug therapy KW - Ofloxacin -- adverse effects KW - HIV Infections -- metabolism KW - Anti-Infective Agents -- administration & dosage KW - Ofloxacin -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70013512?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Pharmacokinetics+and+safety+of+high-dose+and+extended-interval+regimens+of+levofloxacin+in+human+immunodeficiency+virus-infected+patients.&rft.au=Piscitelli%2C+S+C%3BSpooner%2C+K%3BBaird%2C+B%3BChow%2C+A+T%3BFowler%2C+C+L%3BWilliams%2C+R+R%3BNatarajan%2C+J%3BMasur%2C+H%3BWalker%2C+R+E&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1999-09-01&rft.volume=43&rft.issue=9&rft.spage=2323&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Antimicrob Agents Chemother. 1996 Nov;40(11):2483-7 [8913450] Nephron. 1976;16(1):31-41 [1244564] Antimicrob Agents Chemother. 1994 May;38(5):1161-4 [8067756] J Pharm Biomed Anal. 1997 Mar;15(6):765-71 [9172102] Antimicrob Agents Chemother. 1997 Aug;41(8):1765-9 [9257757] Drugs. 1997;54 Suppl 2:8-15; discussion 28-9 [9358195] J Antimicrob Chemother. 1997 Oct;40(4):573-7 [9372428] Clin Infect Dis. 1997 Nov;25(5):1213-21 [9402384] Ann Pharmacother. 1998 Feb;32(2):268-9 [9496417] MMWR Morb Mortal Wkly Rep. 1998 Apr 10;47(13):253-7 [9565485] Antimicrob Agents Chemother. 1997 Oct;41(10):2256-60 [9333057] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of the hematoregulatory peptide SK&F 107647 alone and in combination with amphotericin B against disseminated candidiasis in persistently neutropenic rabbits. AN - 70012465; 10471559 AB - The effects of the hematoregulatory peptide SK&F 107647 were examined in a persistently and profoundly neutropenic rabbit model of disseminated candidiasis in order to determine its potential to enhance resistance against infection and its role as an adjunct to conventional antifungal chemotherapy. In healthy animals, SK&F 107647 elicited a time-dependent increase in CD11b-positive monocytes and neutrophils. When administered to neutropenic rabbits infected with Candida albicans, no significant differences in the number of CFU per gram in any of the tissues tested compared with the number in untreated control rabbits were detected. However, when SK&F 107647 was administered in combination with low doses of amphotericin B, there was a significant reduction in organism burden in the lungs, liver, spleen, and kidneys compared with the burdens in the organs of untreated control animals and in the lungs and kidneys compared with the burdens in the lungs and kidneys of animals treated with amphotericin B alone. These data suggest a potential role for this peptide as adjunctive therapy in combination with conventional antifungal agents in the treatment of disseminated candidiasis in the setting of profound and persistent neutropenia. JF - Antimicrobial agents and chemotherapy AU - Lyman, C A AU - Gonzalez, C AU - Schneider, M AU - Lee, J AU - Walsh, T J AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. lymanc@mail.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 2165 EP - 2169 VL - 43 IS - 9 SN - 0066-4804, 0066-4804 KW - Adjuvants, Immunologic KW - 0 KW - Antifungal Agents KW - Oligopeptides KW - Cytarabine KW - 04079A1RDZ KW - SK&F 107647 KW - 155238-94-1 KW - Amphotericin B KW - 7XU7A7DROE KW - Index Medicus KW - Drug Therapy, Combination KW - Animals KW - Neutropenia -- chemically induced KW - Rabbits KW - Cytarabine -- adverse effects KW - Female KW - Candidiasis -- drug therapy KW - Oligopeptides -- therapeutic use KW - Amphotericin B -- therapeutic use KW - Adjuvants, Immunologic -- therapeutic use KW - Antifungal Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70012465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Effects+of+the+hematoregulatory+peptide+SK%26amp%3BF+107647+alone+and+in+combination+with+amphotericin+B+against+disseminated+candidiasis+in+persistently+neutropenic+rabbits.&rft.au=Lyman%2C+C+A%3BGonzalez%2C+C%3BSchneider%2C+M%3BLee%2C+J%3BWalsh%2C+T+J&rft.aulast=Lyman&rft.aufirst=C&rft.date=1999-09-01&rft.volume=43&rft.issue=9&rft.spage=2165&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Infect Dis. 1992 Sep;15(3):508-24 [1520801] Clin Infect Dis. 1998 Jun;26(6):1266-9 [9636844] Antimicrob Agents Chemother. 1992 Aug;36(8):1626-9 [1329623] Clin Infect Dis. 1993 Apr;16(4):528-30 [8513060] J Clin Microbiol. 1987 May;25(5):931-2 [3294892] Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Clin Infect Dis. 1992 Mar;14 Suppl 1:S139-47 [1562687] Antimicrob Agents Chemother. 1991 Dec;35(12):2625-9 [1667256] Clin Infect Dis. 1993 Oct;17(4):705-7 [8268354] Exp Hematol. 1994 Mar;22(3):239-47 [8112423] J Clin Oncol. 1994 Apr;12(4):827-34 [8151325] Antimicrob Agents Chemother. 1994 Mar;38(3):460-4 [7911289] Immunopharmacology. 1994 May-Jun;27(3):199-206 [7520890] Eur J Clin Microbiol Infect Dis. 1995 Aug;14(8):700-3 [8565989] J Infect Dis. 1996 Jan;173(1):203-11 [8537660] Cytokine. 1996 Jan;8(1):42-8 [8742065] Infect Dis Clin North Am. 1996 Jun;10(2):365-400 [8803625] Infect Immun. 1997 Feb;65(2):564-70 [9009314] J Med Vet Mycol. 1997 Jul-Aug;35(4):243-7 [9292420] Antimicrob Agents Chemother. 1992 Jun;36(6):1225-9 [1416821] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice. AN - 70003171; 10469630 AB - 4-Aminobiphenyl (4-ABP), a potent carcinogen in rodents (liver cancer) and human (bladder cancer), is found as an environmental contaminant and in tobacco smoke. Hemoglobin adducts and lung DNA adducts of 4-ABP are found in tobacco smokers. In vitro metabolism studies with human and rat liver microsomes have shown that CYP1A2 is primarily responsible for catalyzing N-hydroxylation, the initial step in the metabolic activation of 4-ABP. To determine whether this P450 is a rate limiting pathway for hepatocarcinogenesis, CYP1A2-null mice were analyzed at 16 months of age and were compared with wild-type mice in their response to 4-ABP using the neonatal mouse bioassay and two different doses of the carcinogen. Overall differences in incidences of hepatocellular adenoma, carcinoma and preneoplastic foci were not significant between either genotypes or 4-ABP doses used, whereas small, but significant, differences were found for specific types of foci. These results suggest that while CYP1A2 levels may not be rate limiting for 4-ABP metabolism to produce tumors and foci, it may modulate the induction process of some types of liver foci in either a positive or negative manner. In vitro studies using CYP1A2-null and wild-type mouse liver microsomes revealed that CYP1A2 is not the sole P450 required for 4-ABP N-hydroxylation and that another, yet to be identified, P450 is likely to be involved. JF - Carcinogenesis AU - Kimura, S AU - Kawabe, M AU - Ward, J M AU - Morishima, H AU - Kadlubar, F F AU - Hammons, G J AU - Fernandez-Salguero, P AU - Gonzalez, F J AD - Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA. shioko@helix.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1825 EP - 1830 VL - 20 IS - 9 SN - 0143-3334, 0143-3334 KW - Aminobiphenyl Compounds KW - 0 KW - Carcinogens, Environmental KW - Receptors, Aryl Hydrocarbon KW - 2-aminodiphenyl KW - 8LQM58EBRY KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Humans KW - Mice KW - Precancerous Conditions -- enzymology KW - Mice, Knockout KW - Hydroxylation KW - Rats KW - Animals, Newborn KW - Stomach -- pathology KW - Adenoma -- enzymology KW - Biotransformation KW - Precancerous Conditions -- chemically induced KW - Adenoma -- chemically induced KW - Mice, Inbred C57BL KW - Carcinoma -- enzymology KW - Crosses, Genetic KW - Receptors, Aryl Hydrocarbon -- genetics KW - Receptors, Aryl Hydrocarbon -- deficiency KW - Species Specificity KW - Stomach -- enzymology KW - Male KW - Female KW - Organ Size -- drug effects KW - Carcinoma -- chemically induced KW - Cytochrome P-450 CYP1A2 -- physiology KW - Aminobiphenyl Compounds -- pharmacokinetics KW - Cytochrome P-450 CYP1A2 -- genetics KW - Aminobiphenyl Compounds -- toxicity KW - Microsomes, Liver -- enzymology KW - Liver Neoplasms, Experimental -- enzymology KW - Liver Neoplasms, Experimental -- chemically induced KW - Cytochrome P-450 CYP1A2 -- deficiency KW - Carcinogens, Environmental -- toxicity KW - Carcinogens, Environmental -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70003171?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=CYP1A2+is+not+the+primary+enzyme+responsible+for+4-aminobiphenyl-induced+hepatocarcinogenesis+in+mice.&rft.au=Kimura%2C+S%3BKawabe%2C+M%3BWard%2C+J+M%3BMorishima%2C+H%3BKadlubar%2C+F+F%3BHammons%2C+G+J%3BFernandez-Salguero%2C+P%3BGonzalez%2C+F+J&rft.aulast=Kimura&rft.aufirst=S&rft.date=1999-09-01&rft.volume=20&rft.issue=9&rft.spage=1825&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of hamster pregnancy on female protein, a homolog of serum amyloid P component. AN - 69996482; 10460699 AB - Pentraxins such as human serum amyloid P component (SAP) and C reactive protein (CRP) represent an ancient family of proteins that are ubiquitous in nature and have evolved with little change in structure or regulation. The pentraxin in the Syrian hamster (Mesocricetus auratus) is unique because it is preferentially expressed in the female at high constitutive levels and accordingly called female protein (FP) or FP(SAP) due to its close homology with human SAP. The high levels of FP in female serum (100-fold greater than male serum) suggested its role in hamster pregnancy, one of the shortest of any eutherian mammal. We determined the serum FP concentration in pregnant Syrian hamsters and found a marked decrease (>80%) at term with the nadir at parturition with subsequent increase. A similar downregulation of FP was found in the normal female Syrian hamster after injury (acute phase response), so in both cases the assumed beneficial effects were achieved with less, rather than more pentraxin, a paradoxical pentraxin response. The fall in serum FP concentration could represent a response to protect the fetus from the high and potentially toxic level of FP normally found in the female, that is harmful because of its association with amyloidosis. An FP that is 97.5% identical to Syrian hamster FP is found in the Turkish hamster (Mesocricetus brandti), although serum levels in females are much lower, and amyloid is very rare. During pregnancy/parturition of Turkish hamsters, the serum level of FP remained remarkably constant. In a more distantly related hamster, the Armenian hamster (Cricetulus migratorius), serum FP actually increased during pregnancy and at parturition in a manner similar to that found in the Armenian hamster during an acute phase response. The heterogeneity of FP kinetics during pregnancy in these three species of hamster indicates pleomorphic gene structure for regulation of their similar FPs, and suggests that this protein may have a different function in the pregnancy of each species. JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) AU - Coe, J E AU - Vomachka, A J AU - Ross, M J AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA. jcoe@atlas.niaid.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 369 EP - 375 VL - 221 IS - 4 SN - 0037-9727, 0037-9727 KW - Alpha-Globulins KW - 0 KW - Serum Amyloid P-Component KW - female protein, hamster KW - Progesterone KW - 4G7DS2Q64Y KW - C-Reactive Protein KW - 9007-41-4 KW - Index Medicus KW - Phylogeny KW - Animals KW - Labor, Obstetric KW - Progesterone -- pharmacology KW - Humans KW - Gestational Age KW - Gene Expression Regulation KW - Acute-Phase Reaction KW - Species Specificity KW - Female KW - Pregnancy KW - Cricetinae KW - Serum Amyloid P-Component -- analysis KW - Alpha-Globulins -- analysis KW - Serum Amyloid P-Component -- metabolism KW - C-Reactive Protein -- analysis KW - Alpha-Globulins -- metabolism KW - C-Reactive Protein -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69996482?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.atitle=Effect+of+hamster+pregnancy+on+female+protein%2C+a+homolog+of+serum+amyloid+P+component.&rft.au=Coe%2C+J+E%3BVomachka%2C+A+J%3BRoss%2C+M+J&rft.aulast=Coe&rft.aufirst=J&rft.date=1999-09-01&rft.volume=221&rft.issue=4&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.issn=00379727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-10 N1 - Date created - 1999-09-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of an interneuronal population that mediates recurrent inhibition of motoneurons in the developing chick spinal cord. AN - 69990430; 10460262 AB - Studies on the development of synaptic specificity, embryonic activity, and neuronal specification in the spinal cord have all been limited by the absence of a functionally identified interneuron class (defined by its unique set of connections). Here, we identify an interneuron population in the embryonic chick spinal cord that appears to be the avian equivalent of the mammalian Renshaw cell (R-interneurons). These cells receive monosynaptic nicotinic, cholinergic input from motoneuron recurrent collaterals. They make predominately GABAergic connections back onto motoneurons and to other R-interneurons but project rarely to other spinal interneurons. The similarity between the connections of the developing R-interneuron, shortly after circuit formation, and the mature mammalian Renshaw cell raises the possibility that R-interneuronal connections are formed precisely from the onset. Using a newly developed optical approach, we identified the location of R-interneurons in a column, dorsomedial to the motor nucleus. Functional characterization of the R-interneuron population provides the basis for analyses that have so far only been possible for motoneurons. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Wenner, P AU - O'Donovan, M J AD - Section on Developmental Neurobiology, Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 7557 EP - 7567 VL - 19 IS - 17 KW - Receptors, Cholinergic KW - 0 KW - Receptors, Nicotinic KW - gamma-Aminobutyric Acid KW - 56-12-2 KW - Mecamylamine KW - 6EE945D3OK KW - Strychnine KW - H9Y79VD43J KW - Bicuculline KW - Y37615DVKC KW - Index Medicus KW - Bicuculline -- pharmacology KW - Animals KW - Mammals KW - Chick Embryo KW - Morphogenesis KW - gamma-Aminobutyric Acid -- physiology KW - Mecamylamine -- pharmacology KW - Receptors, Nicotinic -- physiology KW - Electric Stimulation KW - Axons -- physiology KW - Nerve Endings -- physiology KW - Evoked Potentials KW - Receptors, Cholinergic -- physiology KW - Strychnine -- pharmacology KW - Cell Communication KW - Species Specificity KW - Nerve Endings -- drug effects KW - Synapses -- physiology KW - Motor Neurons -- physiology KW - Interneurons -- physiology KW - Interneurons -- cytology KW - Motor Neurons -- cytology KW - Spinal Cord -- embryology KW - Spinal Cord -- cytology KW - Interneurons -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69990430?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Identification+of+an+interneuronal+population+that+mediates+recurrent+inhibition+of+motoneurons+in+the+developing+chick+spinal+cord.&rft.au=Wenner%2C+P%3BO%27Donovan%2C+M+J&rft.aulast=Wenner&rft.aufirst=P&rft.date=1999-09-01&rft.volume=19&rft.issue=17&rft.spage=7557&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=1529-2401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of stress genes by low doses of gamma rays. AN - 69989379; 10453082 AB - Using cells of a human myeloid tumor cell line (ML-1), we have detected induction of several stress-responsive genes by doses of gamma rays below 50 cGy. We found a linear dose-response relationship for induction of CDKN1A (formerly known as CIP1/WAF1) and GADD45 mRNA levels over the range of 2-50 cGy, with no evidence of a threshold for induction. Although exposures to 2 and 5 cGy did not result in any detectable reduction in cloning efficiency or increased apoptosis in ML-1 cells, these exposures did produce a transient delay of cells in the phases of the cell cycle in addition to the observed up-regulation of CDKN1A and GADD45. The relative induction of genes such as CDKN1A by radiation doses that produce little toxicity indicates that surviving cells do contribute significantly to the observed stress responses. These studies should provide insight into the molecular responses to physiologically relevant doses that cannot necessarily be extrapolated from high-dose studies. JF - Radiation research AU - Amundson, S A AU - Do, K T AU - Fornace, A J AD - National Institutes of Health, National Cancer Institute, Division of Basic Science, Bethesda, Maryland 20892, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 225 EP - 231 VL - 152 IS - 3 SN - 0033-7587, 0033-7587 KW - Activating Transcription Factors KW - 0 KW - Blood Proteins KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Nuclear Proteins KW - Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Transcription Factors KW - bcl-2-Associated X Protein KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Space life sciences KW - Protein Biosynthesis KW - Cell Survival -- genetics KW - Humans KW - Apoptosis -- radiation effects KW - Leukemia, Myeloid -- genetics KW - Dose-Response Relationship, Radiation KW - RNA, Messenger -- genetics KW - Transcription Factors -- genetics KW - Transcription Factors -- biosynthesis KW - Blood Proteins -- genetics KW - Proto-Oncogene Proteins -- biosynthesis KW - Apoptosis -- genetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Blood Proteins -- biosynthesis KW - Leukemia, Myeloid -- metabolism KW - Leukemia, Myeloid -- pathology KW - Cell Survival -- radiation effects KW - Proto-Oncogene Proteins -- genetics KW - Cyclins -- biosynthesis KW - Gamma Rays KW - Gene Expression Regulation, Leukemic -- radiation effects KW - Proteins -- genetics KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69989379?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Induction+of+stress+genes+by+low+doses+of+gamma+rays.&rft.au=Amundson%2C+S+A%3BDo%2C+K+T%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=1999-09-01&rft.volume=152&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oral nalmefene therapy reduces scratching activity due to the pruritus of cholestasis: a controlled study. AN - 69987797; 10459118 AB - Intravenous naloxone frequently ameliorates the pruritus of cholestasis, but its low oral bioavailability precludes its use as a long-term therapy. Nalmefene is an orally bioavailable opiate antagonist. We assessed the efficacy of oral nalmefene in ameliorating the pruritus of cholestasis. In a prospective controlled study conducted in a tertiary referral hospital, 11 patients with generalized pruritus complicating chronic liver disease were randomized to receive either nalmefene or placebo in a double-blinded fashion for 2-month periods. Scratching activity was measured continuously for 24-hour periods at baseline and at the end of each treatment period. Data on 8 patients who received at least 1 course of nalmefene were available for comparison with corresponding control data, which consisted of observations obtained during a course of placebo and/or at baseline. Nalmefene therapy was associated with a 75% reduction in the geometric mean hourly scratching activity (P <.01) and a decrease in the mean of a visual analogue score of the perception of pruritus in all 8 patients (mean decrease 77%, P <.01). Oral administration of nalmefene can ameliorate pruritus complicating chronic liver disease. JF - Journal of the American Academy of Dermatology AU - Bergasa, N V AU - Alling, D W AU - Talbot, T L AU - Wells, M C AU - Jones, E A AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 431 EP - 434 VL - 41 IS - 3 Pt 1 SN - 0190-9622, 0190-9622 KW - Antipruritics KW - 0 KW - Narcotic Antagonists KW - Tablets KW - Naltrexone KW - 5S6W795CQM KW - nalmefene KW - TOV02TDP9I KW - Index Medicus KW - Administration, Oral KW - Double-Blind Method KW - Humans KW - Adult KW - Pain Measurement KW - Time Factors KW - Cholestasis -- complications KW - Pruritus -- drug therapy KW - Narcotic Antagonists -- administration & dosage KW - Naltrexone -- administration & dosage KW - Narcotic Antagonists -- adverse effects KW - Naltrexone -- adverse effects KW - Naltrexone -- analogs & derivatives KW - Antipruritics -- administration & dosage KW - Pruritus -- etiology KW - Antipruritics -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69987797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Dermatology&rft.atitle=Oral+nalmefene+therapy+reduces+scratching+activity+due+to+the+pruritus+of+cholestasis%3A+a+controlled+study.&rft.au=Bergasa%2C+N+V%3BAlling%2C+D+W%3BTalbot%2C+T+L%3BWells%2C+M+C%3BJones%2C+E+A&rft.aulast=Bergasa&rft.aufirst=N&rft.date=1999-09-01&rft.volume=41&rft.issue=3+Pt+1&rft.spage=431&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Dermatology&rft.issn=01909622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-28 N1 - Date created - 1999-09-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):324-5 [10906663] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. AN - 69986546; 10454578 AB - The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB)-responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process. JF - Molecular and cellular biology AU - Kawamoto, T AU - Sueyoshi, T AU - Zelko, I AU - Moore, R AU - Washburn, K AU - Negishi, M AD - Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 6318 EP - 6322 VL - 19 IS - 9 SN - 0270-7306, 0270-7306 KW - DNA Primers KW - 0 KW - Receptors, Cytoplasmic and Nuclear KW - Trans-Activators KW - Transcription Factors KW - constitutive androstane receptor KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Steroid Hydroxylases KW - EC 1.14.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp2b10 protein, mouse KW - Cytochrome P450 Family 2 KW - Phenobarbital KW - YQE403BP4D KW - Index Medicus KW - Animals KW - Mice, Inbred ICR KW - Cell Nucleus -- metabolism KW - DNA Primers -- genetics KW - Humans KW - Liver -- metabolism KW - Mice KW - Biological Transport, Active -- drug effects KW - Base Sequence KW - Gene Expression Regulation, Enzymologic KW - Liver -- drug effects KW - Enhancer Elements, Genetic KW - In Vitro Techniques KW - Okadaic Acid -- pharmacology KW - Immunohistochemistry KW - Male KW - Cell Line KW - Trans-Activators -- metabolism KW - Phenobarbital -- pharmacology KW - Cytochrome P-450 Enzyme System -- genetics KW - Receptors, Cytoplasmic and Nuclear -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69986546?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Phenobarbital-responsive+nuclear+translocation+of+the+receptor+CAR+in+induction+of+the+CYP2B+gene.&rft.au=Kawamoto%2C+T%3BSueyoshi%2C+T%3BZelko%2C+I%3BMoore%2C+R%3BWashburn%2C+K%3BNegishi%2C+M&rft.aulast=Kawamoto&rft.aufirst=T&rft.date=1999-09-01&rft.volume=19&rft.issue=9&rft.spage=6318&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-10 N1 - Date created - 1999-09-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1999 Mar 5;274(10):6043-6 [10037683] Nature. 1998 Oct 8;395(6702):543-4 [9783576] Cancer Res. 1982 Dec;42(12):4875-917 [6814745] Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 [6828386] EMBO J. 1987 Nov;6(11):3333-40 [3123217] Mol Endocrinol. 1991 Sep;5(9):1215-28 [1663212] Biochem J. 1992 Feb 1;281 ( Pt 3):577-92 [1536639] Mol Cell Biol. 1994 Mar;14(3):1544-52 [8114692] Endocrinology. 1995 Dec;136(12):5685-93 [7588324] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4845-50 [8643491] Biochem J. 1996 Nov 1;319 ( Pt 3):657-67 [8920964] J Biol Chem. 1997 Feb 28;272(9):5774-82 [9038191] J Pharmacol Exp Ther. 1997 Aug;282(2):1122-9 [9262383] J Biol Chem. 1997 Nov 21;272(47):29423-5 [9367997] J Biochem Mol Toxicol. 1998;12(1):3-9 [9414482] Biochem J. 1998 Mar 1;330 ( Pt 2):889-95 [9480906] Endocrinology. 1998 Apr;139(4):1653-61 [9528946] J Biol Chem. 1998 Apr 3;273(14):8528-36 [9525968] Mol Pharmacol. 1998 Apr;53(4):597-601 [9547348] Mol Cell Biol. 1998 Oct;18(10):5652-8 [9742082] Nature. 1998 Oct 8;395(6702):612-5 [9783588] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differing effects of N-methyl-D-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine monkeys. AN - 69983652; 10454475 AB - The antiparkinsonian and antidyskinetic profile of two N-methyl-D-aspartate (NMDA) receptor antagonists, a competitive antagonist, (R)-4-oxo-5-phosphononorvaline (MDL 100,453), and a novel noncompetitive allosteric site antagonist, 4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piper idi ne (Co 101244/PD 174494), was assessed in six levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine-lesioned parkinsonian monkeys. The effects on motor function of these two drugs, alone and in combination with levodopa, were then correlated with NMDA subtype selectivity and apparent affinity for four diheteromeric NMDA receptor subunit combinations expressed in Xenopus oocytes. MDL 100, 453 (300 mg/kg s.c.) by itself increased global motor activity (p =. 0005 versus vehicle) and administered 15 min after a low dose of levodopa/benserazide s.c., MDL 100,453 (50, 300 mg/kg s.c.) showed dose-dependent potentiation of antiparkinsonian responses and also produced dyskinesias. Following injection of a fully effective dose of levodopa, MDL 100,453 (300 mg/kg s.c.) also produced a 25% increase in mean dyskinesia score (p =.04). In contrast, Co 101244 did not change motor activity by itself and only showed a tendency to potentiate the antiparkinsonian response when given in combination with a low dose of levodopa, which did not attain statistical significance. However, with a high dose of levodopa, Co 101244 (0.1, 1 mg/kg s.c.) displayed antidyskinetic effects (67 and 71% reduction, respectively) while sparing levodopa motor benefit. In vitro, MDL 100,453 was an NMDA glutamate-site antagonist, with approximately 5- to 10-fold selectivity for the NR1A/NR2A subtype combination (K(b) = 0.6 microM) versus NR1A in combination with 2B, 2C, or 2D. In contrast, the allosteric site antagonist Co 101244 showed approximately 10,000-fold selectivity for the NR1A/NR2B (IC(50) = 0.026 microM) versus the other three subunit combinations tested. Taken together, the data suggest that the NR2 subunit selectivity profile of NMDA receptor antagonists can play an important role in predicting behavioral outcome and offer more evidence that NR2B-selective NMDA receptor antagonists may be useful agents in the treatment of Parkinson's disease. JF - The Journal of pharmacology and experimental therapeutics AU - Blanchet, P J AU - Konitsiotis, S AU - Whittemore, E R AU - Zhou, Z L AU - Woodward, R M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. blanchet@medent.umontreal.ca Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1034 EP - 1040 VL - 290 IS - 3 SN - 0022-3565, 0022-3565 KW - Antiparkinson Agents KW - 0 KW - Dopamine Agents KW - Excitatory Amino Acid Antagonists KW - Receptors, N-Methyl-D-Aspartate KW - 4-oxo-5-phosphononorvaline KW - 129938-34-7 KW - Levodopa KW - 46627O600J KW - Valine KW - HG18B9YRS7 KW - Index Medicus KW - Animals KW - Macaca fascicularis KW - Valine -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Parkinson Disease, Secondary -- drug therapy KW - Parkinson Disease, Secondary -- physiopathology KW - Rats KW - Xenopus laevis KW - Oocytes -- metabolism KW - Oocytes -- drug effects KW - Valine -- analogs & derivatives KW - Female KW - Male KW - Levodopa -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- biosynthesis KW - Dopamine Agents -- toxicity KW - Dyskinesia, Drug-Induced -- drug therapy KW - MPTP Poisoning KW - Dopamine Agents -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- antagonists & inhibitors KW - Antiparkinson Agents -- pharmacology KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Receptors, N-Methyl-D-Aspartate -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69983652?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Differing+effects+of+N-methyl-D-aspartate+receptor+subtype+selective+antagonists+on+dyskinesias+in+levodopa-treated+1-methyl-4-phenyl-tetrahydropyridine+monkeys.&rft.au=Blanchet%2C+P+J%3BKonitsiotis%2C+S%3BWhittemore%2C+E+R%3BZhou%2C+Z+L%3BWoodward%2C+R+M%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1999-09-01&rft.volume=290&rft.issue=3&rft.spage=1034&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-21 N1 - Date created - 1999-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multisecond oscillations in firing rate in the globus pallidus: synergistic modulation by D1 and D2 dopamine receptors. AN - 69979492; 10454529 AB - The firing rates of many basal ganglia neurons recorded in awake rats oscillate at seconds-to-minutes time scales, and the D1/D2 agonist apomorphine has been shown to robustly modulate these oscillations. The use of selective D1 and D2 antagonists suggested that both these receptor subfamilies are involved in apomorphine's effects. In the present study, spectral analysis revealed that baseline multisecond oscillations were significantly periodic in 71% of globus pallidus neurons. Baseline oscillations had a wide range of periods within the analyzed range, with a population mean of 32 +/- 2 s. Administration of the D1 agonist SKF 81297 (6-chloroPB) at 1.0 or 5.0 mg/kg significantly changed these oscillations, reducing means of spectral peak periods to 14 to 16 s (i.e., increasing oscillatory frequency). This effect was attenuated by D2 antagonist pretreatment. The D2 agonist quinpirole did not cause a significant population change in multisecond periodicities. The strongest effects on multisecond periodicities occurred after combined treatment with SKF 81297 and quinpirole. Low, ineffective doses of SKF 81297 and quinpirole, when combined, produced a significant increase in oscillatory frequency. Also, when quinpirole was administered after an already effective dose of SKF 81297, quinpirole shifted oscillations to an even faster range (typically to periods of <10 s). The dopaminergic control of multisecond periodicities in globus pallidus firing rate demonstrates D1/D2 receptor synergism, in that the effects of D1 agonists are potentiated by and partially dependent on D2 receptor activity. Modulation of multisecond oscillations in firing rate represents a novel means by which dopamine can influence globus pallidus physiology. JF - The Journal of pharmacology and experimental therapeutics AU - Ruskin, D N AU - Bergstrom, D A AU - Walters, J R AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. dnruskin@helix.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1493 EP - 1501 VL - 290 IS - 3 SN - 0022-3565, 0022-3565 KW - Benzazepines KW - 0 KW - Dopamine Agonists KW - Receptors, Dopamine D1 KW - Receptors, Dopamine D2 KW - SK&F 81297 KW - 71636-61-8 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Animals KW - Benzazepines -- pharmacology KW - Dose-Response Relationship, Drug KW - Apomorphine -- pharmacology KW - Neurons -- drug effects KW - Basal Ganglia -- physiology KW - Electrophysiology KW - Rats KW - Rats, Sprague-Dawley KW - Neurons -- physiology KW - Drug Synergism KW - Time Factors KW - Basal Ganglia -- drug effects KW - Oscillometry KW - Receptors, Dopamine D1 -- physiology KW - Dopamine Agonists -- pharmacology KW - Globus Pallidus -- drug effects KW - Receptors, Dopamine D2 -- physiology KW - Globus Pallidus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69979492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Multisecond+oscillations+in+firing+rate+in+the+globus+pallidus%3A+synergistic+modulation+by+D1+and+D2+dopamine+receptors.&rft.au=Ruskin%2C+D+N%3BBergstrom%2C+D+A%3BWalters%2C+J+R&rft.aulast=Ruskin&rft.aufirst=D&rft.date=1999-09-01&rft.volume=290&rft.issue=3&rft.spage=1493&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-21 N1 - Date created - 1999-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preclinical evaluation of newly approved and potential antiepileptic drugs against cocaine-induced seizures. AN - 69979126; 10454489 AB - Seizures and status epilepticus are among the neurological complications of cocaine overdose in humans. The aim of the present study was to evaluate the protective effectiveness and therapeutic index (separation between anticonvulsive and side effect profiles) of 14 newly approved and potential antiepileptic drugs using a murine model of acute cocaine toxicity and the inverted-screen test for behavioral side effect testing. Cocaine (75 mg/kg i.p.) produces clonic seizures (approximately 90% of mice), and conventional antiepileptic drugs have been reported to be either ineffective or only effective at doses producing significant sedative/ataxic effects. Clobazam, flunarizine, lamotrigine, topiramate, and zonisamide were ineffective against seizures up to doses producing significant motor impairment. In contrast, felbamate, gabapentin, loreclezole, losigamone, progabide, remacemide, stiripentol, tiagabine, and vigabatrin produced dose-dependent protection against cocaine-induced convulsions with varied separations between their anticonvulsant and side effect profiles: the protective index values (toxic TD(50)/anticonvulsive ED(50)) ranged from 1.26 (felbamate) to 7.67 (loreclezole), and gabapentin had the highest (protective index >152). Thus, several drugs were identified with greater protective efficacy and reduced motor impairment compared with classic antiepileptic drugs. Based on the proposed mechanism of action of these new anticonvulsants, it is noteworthy that 1) drugs that enhance gamma-aminobutyric acid-mediated neuronal inhibition in a manner distinct from barbiturates and benzodiazepines offer the best protective/behavioral side effect profiles, and 2) functional antagonists of Na(+) and Ca(2+) channels are generally ineffective. Overall, this study provides the first description of the effectiveness of new antiepileptic drugs against experimentally induced cocaine seizures and points to several drugs that deserve clinical scrutiny for this indication. JF - The Journal of pharmacology and experimental therapeutics AU - Gasior, M AU - Ungard, J T AU - Witkin, J M AD - Drug Development Group, Behavioral Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. mgasior@intra.nida.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1148 EP - 1156 VL - 290 IS - 3 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Dopamine Uptake Inhibitors KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Dose-Response Relationship, Drug KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Mice KW - Drug Evaluation, Preclinical -- methods KW - Male KW - Seizures -- chemically induced KW - Dopamine Uptake Inhibitors -- toxicity KW - Anticonvulsants -- toxicity KW - Cocaine -- toxicity KW - Seizures -- prevention & control KW - Anticonvulsants -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69979126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Preclinical+evaluation+of+newly+approved+and+potential+antiepileptic+drugs+against+cocaine-induced+seizures.&rft.au=Gasior%2C+M%3BUngard%2C+J+T%3BWitkin%2C+J+M&rft.aulast=Gasior&rft.aufirst=M&rft.date=1999-09-01&rft.volume=290&rft.issue=3&rft.spage=1148&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-21 N1 - Date created - 1999-09-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eotaxin potentiates antigen-dependent basophil IL-4 production. AN - 69978740; 10453034 AB - Basophils are a major source of IL-4, which is a critical factor in the generation of allergic inflammation. Eotaxin induces chemotaxis mediated through the CC chemokine receptor 3 (CCR3) present on basophils as well as eosinophils and Th2 cells, thereby promoting cell recruitment. To determine whether eotaxin has other proinflammatory activity, we examined the effect of eotaxin on basophil IL-4 expression by flow cytometry. Eotaxin alone had no effect on basophil IL-4 production, but further increased allergen-stimulated IL-4 expression. Eotaxin also enhanced IL-4 release from purified basophils 2- to 4-fold, as determined by ELISA (p < 0.01). Addition of eotaxin to cultures resulted in a 40-fold left shift in the dose response to Ag. This effect was obtained with physiologic concentrations of eotaxin (10 ng/ml), was abrogated by an Ab to the CCR3 receptor, and was noted with other chemokine ligands of CCR3. Additionally, eotaxin augmented IL-3 priming of basophil IL-4 production in a synergistic manner (p < 0.01). In contrast, no priming was observed with either IL-5 or GM-CSF. These results establish a novel function for eotaxin and other chemokine ligands of CCR3: the potentiation of Ag-mediated IL-4 production in basophils, and suggest a potential nonchemotactic role for CC chemokines in the pathogenesis and amplification of inflammation. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Devouassoux, G AU - Metcalfe, D D AU - Prussin, C AD - Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 2877 EP - 2882 VL - 163 IS - 5 SN - 0022-1767, 0022-1767 KW - Adjuvants, Immunologic KW - 0 KW - Antigens KW - CCL11 protein, human KW - CCR3 protein, human KW - Chemokine CCL11 KW - Chemokines, CC KW - Chemotactic Factors, Eosinophil KW - Cytokines KW - Interleukin-3 KW - Receptors, CCR3 KW - Receptors, Chemokine KW - Interleukin-4 KW - 207137-56-2 KW - Abridged Index Medicus KW - Index Medicus KW - Hypersensitivity -- immunology KW - Interleukin-3 -- pharmacology KW - Humans KW - Dose-Response Relationship, Immunologic KW - Receptors, Chemokine -- physiology KW - Drug Synergism KW - Asthma -- immunology KW - Cytokines -- pharmacology KW - Antigens -- physiology KW - Interleukin-4 -- biosynthesis KW - Chemotactic Factors, Eosinophil -- pharmacology KW - Adjuvants, Immunologic -- pharmacology KW - Basophils -- metabolism KW - Basophils -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69978740?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Eotaxin+potentiates+antigen-dependent+basophil+IL-4+production.&rft.au=Devouassoux%2C+G%3BMetcalfe%2C+D+D%3BPrussin%2C+C&rft.aulast=Devouassoux&rft.aufirst=G&rft.date=1999-09-01&rft.volume=163&rft.issue=5&rft.spage=2877&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-14 N1 - Date created - 1999-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment. AN - 69974985; 10453025 AB - Mice deficient in lymphotoxin (LT)-alpha lack peripheral lymph nodes and Peyer's patches and have profound defects in development of follicular dendritic cell networks, germinal center formation, and T/B cell segregation in the spleen. Although LTalpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LTalpha for NK cell functions is largely unknown. To address this issue, we have assessed NK cell functions in LTalpha-deficient mice by evaluating tumor models with known requirements for NK cells to control their growth and metastasis. Syngeneic B16F10 melanoma cells inoculated s.c. grew more rapidly in LTalpha-/- mice than in the wild-type littermates, and the formation of experimental pulmonary metastases was significantly enhanced in LTalpha-/- mice. Although LTalpha-/- mice exhibited almost a normal total number of NK cells in spleen, they showed an impaired recruitment of NK cells to lung and liver. Additionally, lytic NK cells were not efficiently produced from LTalpha-/- bone marrow cells in vitro in the presence of IL-2 and IL-15. These data suggest that LTalpha signaling may be involved in the maturation and recruitment of NK cells and may play an important role in antitumor surveillance. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ito, D AU - Back, T C AU - Shakhov, A N AU - Wiltrout, R H AU - Nedospasov, S A AD - Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Science Applications International Corp.-Frederick, National Cancer Institute-Frederic Cancer Research and Development Center, MD 21702, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 2809 EP - 2815 VL - 163 IS - 5 SN - 0022-1767, 0022-1767 KW - Lymphotoxin-alpha KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Spleen -- cytology KW - Carcinoma, Lewis Lung KW - Melanoma, Experimental KW - Immunologic Deficiency Syndromes -- genetics KW - Bone Marrow Cells -- immunology KW - Mice KW - Mice, Knockout KW - Immunologic Deficiency Syndromes -- immunology KW - Lymphocyte Activation -- genetics KW - Hematopoietic Stem Cells -- immunology KW - Cell Division -- immunology KW - Organ Specificity -- genetics KW - Mice, Inbred C57BL KW - Spleen -- immunology KW - Organ Specificity -- immunology KW - Cell Division -- genetics KW - Mutagenesis, Site-Directed KW - Lymphotoxin-alpha -- genetics KW - Cell Movement -- immunology KW - Lung Neoplasms -- secondary KW - Lung Neoplasms -- immunology KW - Lung Neoplasms -- genetics KW - Cytotoxicity, Immunologic -- genetics KW - Cell Movement -- genetics KW - Killer Cells, Natural -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69974985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.genre=dissertations+%26+theses&rft.jtitle=&rft.atitle=&rft.au=Gitau%2C+Samson+Njuguna&rft.aulast=Gitau&rft.aufirst=Samson&rft.date=1994-01-01&rft.volume=&rft.issue=&rft.spage=&rft.isbn=&rft.btitle=&rft.title=A+comparative+study+of+the+transmission%2C+actualization+and+stabilization+of+oral+traditions%3A+An+examination+of+traditions+of+circumcision+in+Africa+and+ancient+Israel&rft.issn=&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-14 N1 - Date created - 1999-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of two rapid assays for detection of Clostridium difficile toxin A in stool specimens. AN - 69972687; 10449503 AB - Rapid laboratory diagnosis of Clostridium difficile-associated diarrhea (CDAD) is highly desirable in the setting of hospital cost containment. We tested 654 stool specimens to compare the performance of two assays for rapid detection of toxin A, the Immunocard Toxin A test (Meridian Diagnostics, Inc.) and the Culturette Brand Toxin CD enzyme immunoassay (EIA) (Becton Dickinson Microbiology Systems), with a cytotoxin assay (Cytotoxi Test; Advanced Clinical Diagnostics) and culture on cycloserine-cefoxitin-fructose agar followed by determination of the production of toxins A and B. A chart review was performed for patients whose stool specimens provided positive results on one to three of the assays. With the "gold standard" of all four assays positive or chart review evidence of CDAD, 97 (14.8%) stool specimens were positive by one or more assays and 557 (85.2%) were negative by all methods. Total agreement for all assays was 90.5% (592 of 654). The sensitivity, specificity, positive predictive value, and negative predictive value for toxigenic culture were 94.7, 98.6, 87.1, and 99.5%, respectively, for toxigenic culture; 87.7, 98.6, 86.2, and 98.8%, respectively, for the cytotoxin assay; 71.9, 99.3, 91.1, and 97.3%, respectively, for the Immunocard; and 68.4, 99.1, 88.6, and 96.9%, respectively, for the Culturette EIA. While easy to perform and highly specific, these rapid assays do not appear to be sufficient for accurate diagnosis of CDAD. JF - Journal of clinical microbiology AU - Fedorko, D P AU - Engler, H D AU - O'Shaughnessy, E M AU - Williams, E C AU - Reichelderfer, C J AU - Smith, W I AD - Microbiology Service, Clinical Pathology Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. dfedorko@nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 3044 EP - 3047 VL - 37 IS - 9 SN - 0095-1137, 0095-1137 KW - Bacterial Toxins KW - 0 KW - Enterotoxins KW - tcdA protein, Clostridium difficile KW - Index Medicus KW - Humans KW - Immunoenzyme Techniques KW - Diarrhea -- diagnosis KW - Feces -- microbiology KW - Clostridium difficile -- pathogenicity KW - Enterotoxins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69972687?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+microbiology&rft.atitle=Evaluation+of+two+rapid+assays+for+detection+of+Clostridium+difficile+toxin+A+in+stool+specimens.&rft.au=Fedorko%2C+D+P%3BEngler%2C+H+D%3BO%27Shaughnessy%2C+E+M%3BWilliams%2C+E+C%3BReichelderfer%2C+C+J%3BSmith%2C+W+I&rft.aulast=Fedorko&rft.aufirst=D&rft.date=1999-09-01&rft.volume=37&rft.issue=9&rft.spage=3044&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-02 N1 - Date created - 1999-09-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Diagn Microbiol Infect Dis. 1988 Jun;10(2):85-91 [3066571] J Clin Microbiol. 1992 May;30(5):1085-8 [1583104] Infect Immun. 1992 Nov;60(11):4633-9 [1398977] J Clin Microbiol. 1993 Apr;31(4):963-7 [8463404] Clin Microbiol Rev. 1993 Jul;6(3):251-65 [8358706] N Engl J Med. 1994 Jan 27;330(4):257-62 [8043060] Gastroenterology. 1998 Dec;115(6):1329-34 [9834258] J Clin Microbiol. 1996 Nov;34(11):2718-21 [8897171] Clin Infect Dis. 1997 Mar;24(3):324-33 [9114180] J Clin Microbiol. 1997 May;35(5):1258-9 [9114419] J Clin Microbiol. 1997 Nov;35(11):3007 [9350782] Clin Infect Dis. 1998 Feb;26(2):410-2 [9502463] Eur J Clin Microbiol Infect Dis. 1996 Apr;15(4):330-6 [8781886] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Child psychopathology risk factors for drug abuse: overview. AN - 69964703; 10446678 AB - Introduces the special section on Child Psychopathology Risk Factors for Substance Use Disorders. This article summarizes important principles, the current literature, contributions to this section, and issues for future research. Psychopathological conditions are strongly associated with substance use disorders, and some childhood psychopathological conditions may constitute precursors to this comorbidity. Conduct disorder constitutes a strong risk factor for substance use disorders, and bipolar disorder, although more rare, may also constitute a significant risk. Data for other child psychiatric conditions are mixed or lacking; however, important subgroups may be at risk and merit further attention. Underlying characteristics, such as temperament and self-regulation, merit further study as possible explanatory variables. Such studies hold the key for targeting and improving preventive and therapeutic interventions. JF - Journal of clinical child psychology AU - Weinberg, N Z AU - Glantz, M D AD - National Institute on Drug Abuse, Bethesda, MD 20892-9589, USA. nw46w@nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 290 EP - 297 VL - 28 IS - 3 SN - 0047-228X, 0047-228X KW - Index Medicus KW - Psychology, Child KW - Risk Factors KW - Humans KW - Child KW - Comorbidity KW - Substance-Related Disorders -- etiology KW - Substance-Related Disorders -- psychology KW - Mental Disorders -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69964703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+child+psychology&rft.atitle=Child+psychopathology+risk+factors+for+drug+abuse%3A+overview.&rft.au=Weinberg%2C+N+Z%3BGlantz%2C+M+D&rft.aulast=Weinberg&rft.aufirst=N&rft.date=1999-09-01&rft.volume=28&rft.issue=3&rft.spage=290&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+child+psychology&rft.issn=0047228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic and DNA binding properties of purified WRN protein: high affinity binding to single-stranded DNA but not to DNA damage induced by 4NQO. AN - 69964186; 10446247 AB - Mutations in the WRN gene result in Werner syndrome, an autosomal recessive disease in which many characteristics of aging are accelerated. A probable role in some aspect of DNA metabolism is suggested by the primary sequence of the WRN gene product. A recombinant His-tagged WRN protein (WRNp) was overproduced in insect cells using the baculovirus system and purified to near homogeneity by several chromatographic steps. This purification scheme removes both nuclease and topoisomerase contaminants that persist following a single Ni(2+)affinity chromatography step and allows for unambiguous interpretation of WRNp enzymatic activities on DNA substrates. Purified WRNp has DNA-dependent ATPase and helicase activities consistent with its homology to the RecQ subfamily of proteins. The protein also binds with higher affinity to single-stranded DNA than to double-stranded DNA. However, WRNp has no higher affinity for various types of DNA damage, including adducts formed during 4NQO treatment, than for undamaged DNA. Our results confirm that WRNp has a role in DNA metabolism, although this role does not appear to be the specific recognition of damage in DNA. JF - Nucleic acids research AU - Orren, D K AU - Brosh, R M AU - Nehlin, J O AU - Machwe, A AU - Gray, M D AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 3557 EP - 3566 VL - 27 IS - 17 KW - DNA, Complementary KW - 0 KW - DNA, Single-Stranded KW - Recombinant Proteins KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - DNA KW - 9007-49-2 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Recombinant Proteins -- isolation & purification KW - Baculoviridae -- genetics KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Humans KW - Adenosine Triphosphatases -- metabolism KW - Time Factors KW - Hydrolysis KW - DNA, Complementary -- analysis KW - DNA, Single-Stranded -- metabolism KW - DNA Helicases -- chemistry KW - 4-Nitroquinoline-1-oxide -- pharmacology KW - DNA Helicases -- metabolism KW - DNA Damage KW - DNA Helicases -- isolation & purification KW - DNA -- metabolism KW - DNA Helicases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69964186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Enzymatic+and+DNA+binding+properties+of+purified+WRN+protein%3A+high+affinity+binding+to+single-stranded+DNA+but+not+to+DNA+damage+induced+by+4NQO.&rft.au=Orren%2C+D+K%3BBrosh%2C+R+M%3BNehlin%2C+J+O%3BMachwe%2C+A%3BGray%2C+M+D%3BBohr%2C+V+A&rft.aulast=Orren&rft.aufirst=D&rft.date=1999-09-01&rft.volume=27&rft.issue=17&rft.spage=3557&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion errors generated during replication of CAG repeats. AN - 69959927; 10446236 AB - Triplet repeat sequence instability is associated with hereditary neurological diseases and with certain types of cancer. Here we study one form of this instability, deletion of triplet repeats during replication of template (CAG)(n)sequences by DNA polymerases. To monitor loss of triplet codons, we inserted (CAG)(9)and (CAG)(17)repeats into the lacZ sequence in M13mp2 and changed one repeat to a TAG codon to yield DNA substrates with colorless plaque phenotypes. Templates containing these inserts within gaps were copied and errors were scored as blue plaque Lac revertants whose DNA was sequenced to determine if loss of the TAG codon resulted from substitutions or deletions. DNA synthesis by either DNA polymerase beta or exonuclease-deficient T7 DNA polymerase produced deletions involving loss of from 1 to 8 of 9 or 15 of 17 repeats. Thus, these polymerases utilize misaligned template-primers containing from 3 to 45 extra template strand nucleotides. Deletion frequencies were much higher than substitution frequencies at the TAG codon in certain repeats, indicating that triplet repeats are at high risk for mutation in the absence of error correction. Proofreading-proficient T7 DNA polymerase generated deletions at 2- to 10-fold lower frequencies than did its exonuclease-deficient derivative. This suggests that misaligned triplet repeat sequences are subject to proofreading, but at reduced efficiency compared to editing of single-base mismatches. JF - Nucleic acids research AU - Kroutil, L C AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, USA. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 3481 EP - 3486 VL - 27 IS - 17 KW - Thioredoxins KW - 52500-60-4 KW - DNA Polymerase beta KW - EC 2.7.7.- KW - bacteriophage T7 induced DNA polymerase KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Index Medicus KW - Lac Operon -- genetics KW - Base Sequence KW - DNA Repair KW - Humans KW - Molecular Sequence Data KW - Thioredoxins -- metabolism KW - Escherichia coli -- enzymology KW - DNA Polymerase beta -- metabolism KW - Mutagenesis KW - DNA-Directed DNA Polymerase -- metabolism KW - Trinucleotide Repeats -- genetics KW - DNA Replication KW - Sequence Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69959927?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Deletion+errors+generated+during+replication+of+CAG+repeats.&rft.au=Kroutil%2C+L+C%3BKunkel%2C+T+A&rft.aulast=Kroutil&rft.aufirst=L&rft.date=1999-09-01&rft.volume=27&rft.issue=17&rft.spage=3481&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=1362-4962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss. AN - 69941373; 10433913 AB - All vertebrates have an egg shell that surrounds ovulated eggs and plays critical roles in gamete recognition. This extracellular matrix is known as the zona pellucida in eutherian mammals and consists of three glycoproteins, ZP1, ZP2 and ZP3 in the mouse. To investigate the role of ZP1 in fertilization and early development, we have used targeted mutagenesis in embryonic stem cells to create mouse lines (Zp1(tm/tm)) lacking ZP1. Although a zona pellucida composed of ZP2 and ZP3 was formed around growing Zp1(tm/tm) oocytes, the matrix was more loosely organized than zonae around normal oocytes. In some Zp1 null follicles, this structural abnormality resulted in ectopic clusters of granulosa cells, lodged between the zona matrix and the oolemma, that perturbed normal folliculogenesis. Comparable numbers of eggs were ovulated from Zp1 null females and normal females following hormonal stimulation. However, after mating with males, fewer two-cell embryos were recovered from Zp1 null females, and their litters were significantly smaller than those produced by normal mice. Therefore, although mouse ZP1 is not essential for sperm binding or fertilization, it is required for the structural integrity of the zona pellucida to minimize precocious hatching and reduced fecundity. JF - Development (Cambridge, England) AU - Rankin, T AU - Talbot, P AU - Lee, E AU - Dean, J AD - Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health Bethesda, Maryland 20892, USA. tr44x@nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 3847 EP - 3855 VL - 126 IS - 17 SN - 0950-1991, 0950-1991 KW - Egg Proteins KW - 0 KW - Membrane Glycoproteins KW - Receptors, Cell Surface KW - Zona Pellucida Glycoproteins KW - Zp1 protein, mouse KW - Zp2 protein, mouse KW - Zp3 protein, mouse KW - Index Medicus KW - Animals KW - Ovary -- abnormalities KW - Fetal Death -- genetics KW - Embryonic and Fetal Development -- physiology KW - Mice KW - Pregnancy KW - Mice, Knockout KW - In Situ Hybridization KW - Embryonic and Fetal Development -- genetics KW - Fertility -- genetics KW - Female KW - Male KW - Microscopy, Electron, Scanning KW - Zona Pellucida -- physiology KW - Egg Proteins -- physiology KW - Membrane Glycoproteins -- physiology KW - Egg Proteins -- genetics KW - Zona Pellucida -- ultrastructure KW - Membrane Glycoproteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69941373?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Abnormal+zonae+pellucidae+in+mice+lacking+ZP1+result+in+early+embryonic+loss.&rft.au=Rankin%2C+T%3BTalbot%2C+P%3BLee%2C+E%3BDean%2C+J&rft.aulast=Rankin&rft.aufirst=T&rft.date=1999-09-01&rft.volume=126&rft.issue=17&rft.spage=3847&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-28 N1 - Date created - 1999-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Using pooled exposure assessment to improve efficiency in case-control studies. AN - 69512592; 11314998 AB - Assays can be so expensive that interesting hypotheses become impractical to study epidemiologically. One need not, however, perform an assay for everyone providing a biological specimen. We propose pooling equal-volume aliquots from randomly grouped sets of cases and randomly grouped sets of controls, and then assaying the smaller number of pooled samples. If an effect modifier is of concern, the pooling can be done within strata defined by that variable. For covariates assessed on individuals (e.g., questionnaire data), set-based counterparts are calculated by adding the values for the individuals in each set. The pooling set then becomes the unit of statistical analysis. We show that, with appropriate specification of a set-based logistic model, standard software yields a valid estimated exposure odds ratio, provided the multiplicative formulation is correct. Pooling minimizes the depletion of irreplaceable biological specimens and can enable additional exposures to be studied economically. Statistical power suffers very little compared with the usual, individual-based analysis. In settings where high assay costs constrain the number of people an investigator can afford to study, specimen pooling can make it possible to study more people and hence improve the study's statistical power with no increase in cost. JF - Biometrics AU - Weinberg, C R AU - Umbach, D M AD - Biostatistics Branch, MD A3-03, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. weinberg@niehs.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 718 EP - 726 VL - 55 IS - 3 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Animals KW - Odds Ratio KW - Random Allocation KW - Logistic Models KW - Humans KW - Environmental Exposure KW - Environmental Monitoring -- statistics & numerical data KW - Biometry KW - Case-Control Studies UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69512592?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Using+pooled+exposure+assessment+to+improve+efficiency+in+case-control+studies.&rft.au=Weinberg%2C+C+R%3BUmbach%2C+D+M&rft.aulast=Weinberg&rft.aufirst=C&rft.date=1999-09-01&rft.volume=55&rft.issue=3&rft.spage=718&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modeling tumor onset and multiplicity using transition models with latent variables. AN - 69507389; 11315036 AB - We describe a method for modeling carcinogenicity from animal studies where the data consist of counts of the number of tumors present over time. The research is motivated by applications to transgenic rodent studies, which have emerged as an alternative to chronic bioassays for screening possible carcinogens. In transgenic mouse studies, the endpoint of interest is frequently skin papilloma, with weekly examinations determining how many papillomas each animal has at a particular point in time. It is assumed that each animal has two unobservable latent variables at each time point. The first indicates whether or not the tumors are in a multiplying state and the second is the potential number of additional tumors if the tumors are in a multiplying state. The product of these variables follows a zero-inflated Poisson distribution, and the EM algorithm can be used to maximize the observed-data pseudo-likelihood, based on the latent variables. A generalized estimating equations robust variance estimator adjusts for dependency among outcomes within individual animals. The method is applied to testing for a dose-related trend in both tumor incidence and multiplicity in carcinogenicity studies. JF - Biometrics AU - Dunson, D B AU - Haseman, J K AD - Biostatistics Branch, NIEHS, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 965 EP - 970 VL - 55 IS - 3 SN - 0006-341X, 0006-341X KW - Carcinogens KW - 0 KW - Benzene KW - J64922108F KW - Index Medicus KW - Skin Neoplasms -- genetics KW - Animals KW - Biometry KW - Skin Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Benzene -- toxicity KW - Algorithms KW - Mice KW - Papilloma -- genetics KW - Mice, Transgenic KW - Papilloma -- chemically induced KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Neoplasms, Experimental -- genetics KW - Models, Statistical KW - Models, Biological KW - Carcinogenicity Tests -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69507389?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Modeling+tumor+onset+and+multiplicity+using+transition+models+with+latent+variables.&rft.au=Dunson%2C+D+B%3BHaseman%2C+J+K&rft.aulast=Dunson&rft.aufirst=D&rft.date=1999-09-01&rft.volume=55&rft.issue=3&rft.spage=965&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-08-16 N1 - Date created - 2001-04-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. AN - 69434730; 10677042 AB - There is great interest in discovering new targets for pain therapy since current methods of analgesia are often only partially successful. Although protein kinase C (PKC) enhances nociceptor function, it is not known which PKC isozymes contribute. Here, we show that epinephrine-induced mechanical and thermal hyperalgesia and acetic acid-associated hyperalgesia are markedly attenuated in PKCepsilon mutant mice, but baseline nociceptive thresholds are normal. Moreover, epinephrine-, carrageenan-, and nerve growth factor- (NGF-) induced hyperalgesia in normal rats, and epinephrine-induced enhancement of tetrodotoxin-resistant Na+ current (TTX-R I(Na)) in cultured rat dorsal root ganglion (DRG) neurons, are inhibited by a PKCepsilon-selective inhibitor peptide. Our findings indicate that PKCepsilon regulates nociceptor function and suggest that PKCepsilon inhibitors could prove useful in the treatment of pain. JF - Neuron AU - Khasar, S G AU - Lin, Y H AU - Martin, A AU - Dadgar, J AU - McMahon, T AU - Wang, D AU - Hundle, B AU - Aley, K O AU - Isenberg, W AU - McCarter, G AU - Green, P G AU - Hodge, C W AU - Levine, J D AU - Messing, R O AD - Department of Internal Medicine and Oral Surgery, National Institutes of Health/University of California, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 253 EP - 260 VL - 24 IS - 1 SN - 0896-6273, 0896-6273 KW - Analgesics KW - 0 KW - Enzyme Inhibitors KW - Isoenzymes KW - Sodium Channels KW - Tetrodotoxin KW - 4368-28-9 KW - Carrageenan KW - 9000-07-1 KW - Nerve Growth Factor KW - 9061-61-4 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Acetic Acid KW - Q40Q9N063P KW - Epinephrine KW - YKH834O4BH KW - Index Medicus KW - Hyperalgesia -- genetics KW - Animals KW - Hyperalgesia -- etiology KW - Sodium Channels -- physiology KW - Mice KW - Rats KW - Hot Temperature KW - Analgesia KW - Tetrodotoxin -- pharmacology KW - Sodium Channels -- drug effects KW - Protein Kinase C -- metabolism KW - Protein Kinase C -- genetics KW - Nociceptors -- physiology KW - Mutation KW - Isoenzymes -- genetics KW - Signal Transduction KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69434730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuron&rft.atitle=A+novel+nociceptor+signaling+pathway+revealed+in+protein+kinase+C+epsilon+mutant+mice.&rft.au=Khasar%2C+S+G%3BLin%2C+Y+H%3BMartin%2C+A%3BDadgar%2C+J%3BMcMahon%2C+T%3BWang%2C+D%3BHundle%2C+B%3BAley%2C+K+O%3BIsenberg%2C+W%3BMcCarter%2C+G%3BGreen%2C+P+G%3BHodge%2C+C+W%3BLevine%2C+J+D%3BMessing%2C+R+O&rft.aulast=Khasar&rft.aufirst=S&rft.date=1999-09-01&rft.volume=24&rft.issue=1&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Neuron&rft.issn=08966273&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-25 N1 - Date created - 2000-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial. AN - 69417103; 10650806 AB - Although the use of salvage chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial, pretreated symptomatic patients often need some kind of treatment to achieve symptoms relief. Gemcitabine is one of the most active new drugs in advanced NSCLC and preliminary reports suggest that it is active also in patients previously treated with platinum compounds. to evaluate activity and toxicity and the effect on quality of life of gemcitabine in platinum-pretreated patients with advanced NSCLC. single-stage phase 2 trial with p0 = 5%, p1 = 20%, alfa = 5%, beta = 10%; 34 patients required and 4 objective responses expected to warrant further studies. Gemcitabine was administered at dose of 1000 mg/m2, i.v., d 18-15, every 4 weeks, for a maximum of 6 cycles. Quality of life was measured by EORTC C-30 and LC-13 questionnaires. from September 1996 to July 1998, 30 patients have been enrolled. There were 6 (20% exact 95% CI 8-39%) partial responses (2 responses were in pts with brain metastases and 2 in patients progressed during first-line chemotherapy). All patients (but one died because myocardial infarction, progressed; median time to progression was 10 weeks (95% CI 7-12); 28 patients died; median survival was 22 weeks (95% CI 17-29). Quality of life analysis showed no significant change but for the improvement of cough after 3 cycles of chemotherapy. There was no severe toxicity. gemcitabine is active as second line for patients with advanced NSCLC who received platinum-based first line treatment. In view of such results randomized trials comparing gemcitabine versus best supportive care are warranted. JF - Anticancer research AU - Gridelli, C AU - Perrone, F AU - Gallo, C AU - Rossi, A AU - Barletta, E AU - Barzelloni, M L AU - Creazzola, S AU - Gatani, T AU - Fiore, F AU - Guida, C AU - Scognamiglio, F AD - National Cancer Institute, Italy. cgridelli@sirio-oncology.it PY - 1999 SP - 4535 EP - 4538 VL - 19 IS - 5C SN - 0250-7005, 0250-7005 KW - Antimetabolites, Antineoplastic KW - 0 KW - Deoxycytidine KW - 0W860991D6 KW - gemcitabine KW - B76N6SBZ8R KW - Index Medicus KW - Humans KW - Adult KW - Treatment Outcome KW - Quality of Life KW - Aged KW - Middle Aged KW - Male KW - Female KW - Deoxycytidine -- analogs & derivatives KW - Lung Neoplasms -- drug therapy KW - Deoxycytidine -- therapeutic use KW - Carcinoma, Non-Small-Cell Lung -- drug therapy KW - Antimetabolites, Antineoplastic -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69417103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anticancer+research&rft.atitle=Single-agent+gemcitabine+as+second-line+treatment+in+patients+with+advanced+non+small+cell+lung+cancer+%28NSCLC%29%3A+a+phase+II+trial.&rft.au=Gridelli%2C+C%3BPerrone%2C+F%3BGallo%2C+C%3BRossi%2C+A%3BBarletta%2C+E%3BBarzelloni%2C+M+L%3BCreazzola%2C+S%3BGatani%2C+T%3BFiore%2C+F%3BGuida%2C+C%3BScognamiglio%2C+F&rft.aulast=Gridelli&rft.aufirst=C&rft.date=1999-09-01&rft.volume=19&rft.issue=5C&rft.spage=4535&rft.isbn=&rft.btitle=&rft.title=Anticancer+research&rft.issn=02507005&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-22 N1 - Date created - 2000-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Atovaquone suspension in HIV-infected volunteers: pharmacokinetics, pharmacodynamics, and TMP-SMX interaction study. AN - 69372021; 10610011 AB - To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV). Open-label, nonrandomized study. Two clinical research centers. Twenty-two HIV-infected volunteers with a median CD4 cell count of 37 cells/mm3. Patients received atovaquone suspension fasting or fed for 2-week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long-term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim-sulfamethoxazole (TMP-SMX). Average steady-state atovaquone concentrations at 500 mg were 6.7 +/- 3.2 microg/ml fasted and 11.3 +/- 5.0 microg/ml with food; at 750 mg, 9.9 +/- 7.1 microg/ml fasted and 12.5 +/- 5.9 microg/ml with food; at 1000 mg, 9.7 +/- 4.3 microg/ml fasted and 13.6 +/- 5.0 microg/ml with food; and at 1500 mg, 21.1 +/- 5.0 microg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3- to 1.7-fold increase in values. Average steady-state concentrations were less than 10 microg/ml in 21% and more than 15 microg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 microg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP-SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%). Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia. JF - Pharmacotherapy AU - Falloon, J AU - Sargent, S AU - Piscitelli, S C AU - Bechtel, C AU - LaFon, S W AU - Sadler, B AU - Walker, R E AU - Kovacs, J A AU - Polis, M A AU - Davey, R T AU - Lane, H C AU - Masur, H AD - National Institute of Allergy and Infectious Diseases and the Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1880, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 1050 EP - 1056 VL - 19 IS - 9 SN - 0277-0008, 0277-0008 KW - Antifungal Agents KW - 0 KW - Naphthoquinones KW - Trimethoprim, Sulfamethoxazole Drug Combination KW - 8064-90-2 KW - Atovaquone KW - Y883P1Z2LT KW - Index Medicus KW - AIDS/HIV KW - Pneumonia, Pneumocystis -- prevention & control KW - Humans KW - Trimethoprim, Sulfamethoxazole Drug Combination -- pharmacokinetics KW - Food-Drug Interactions KW - Adult KW - Middle Aged KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Fasting KW - AIDS-Related Opportunistic Infections -- metabolism KW - Male KW - Female KW - Naphthoquinones -- pharmacokinetics KW - Antifungal Agents -- pharmacokinetics KW - Antifungal Agents -- adverse effects KW - Naphthoquinones -- administration & dosage KW - Naphthoquinones -- adverse effects KW - Antifungal Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69372021?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacotherapy&rft.atitle=Atovaquone+suspension+in+HIV-infected+volunteers%3A+pharmacokinetics%2C+pharmacodynamics%2C+and+TMP-SMX+interaction+study.&rft.au=Falloon%2C+J%3BSargent%2C+S%3BPiscitelli%2C+S+C%3BBechtel%2C+C%3BLaFon%2C+S+W%3BSadler%2C+B%3BWalker%2C+R+E%3BKovacs%2C+J+A%3BPolis%2C+M+A%3BDavey%2C+R+T%3BLane%2C+H+C%3BMasur%2C+H&rft.aulast=Falloon&rft.aufirst=J&rft.date=1999-09-01&rft.volume=19&rft.issue=9&rft.spage=1050&rft.isbn=&rft.btitle=&rft.title=Pharmacotherapy&rft.issn=02770008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-04 N1 - Date created - 2000-02-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Frederick J. de Serres: the years at the Research Triangle Park (1972-1995). AN - 69340566; 10610430 JF - Mutation research AU - Malling, H V AD - NIEHS, Laboratory of Toxicology, Environmental Toxicology Program, Research Triangle Park, NC 27709-2233, USA. malling@niehs.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 69 EP - 75 VL - 437 IS - 2 SN - 0027-5107, 0027-5107 KW - Index Medicus KW - History of medicine KW - de Serres KW - United States KW - Neurospora crassa -- genetics KW - Animals KW - History, 20th Century KW - Toxicology -- history KW - Research -- history KW - Humans KW - North Carolina KW - National Institutes of Health (U.S.) KW - Genetics, Microbial -- history KW - Mutation KW - Genetics -- history UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69340566?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=Frederick+J.+de+Serres%3A+the+years+at+the+Research+Triangle+Park+%281972-1995%29.&rft.au=Malling%2C+H+V&rft.aulast=Malling&rft.aufirst=H&rft.date=1999-09-01&rft.volume=437&rft.issue=2&rft.spage=69&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-09 N1 - Date created - 1999-12-09 N1 - Date revised - 2017-01-13 N1 - People - de Serres N1 - Last updated - 2017-01-18 N1 - SubjectsTermNotLitGenreText - de Serres ER - TY - JOUR T1 - Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. AN - 69282184; 10559937 AB - The generation of animals lacking SMAD proteins, which transduce signals from transforming growth factor-beta (TGF-beta), has made it possible to explore the contribution of the SMAD proteins to TGF-beta activity in vivo. Here we report that, in contrast to predictions made on the basis of the ability of exogenous TGF-beta to improve wound healing, Smad3-null (Smad3ex8/ex8) mice paradoxically show accelerated cutaneous wound healing compared with wild-type mice, characterized by an increased rate of re-epithelialization and significantly reduced local infiltration of monocytes. Smad3ex8/ex8 keratinocytes show altered patterns of growth and migration, and Smad3ex8/ex8 monocytes exhibit a selectively blunted chemotactic response to TGF-beta. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of tissue repair and in the modulation of keratinocyte and monocyte function in vivo. JF - Nature cell biology AU - Ashcroft, G S AU - Yang, X AU - Glick, A B AU - Weinstein, M AU - Letterio, J L AU - Mizel, D E AU - Anzano, M AU - Greenwell-Wild, T AU - Wahl, S M AU - Deng, C AU - Roberts, A B AD - Laboratory of Cell Regulation and Carcinogenesis, NCI, Bethesda, Maryland 20892-5055, USA. Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 260 EP - 266 VL - 1 IS - 5 SN - 1465-7392, 1465-7392 KW - DNA-Binding Proteins KW - 0 KW - Smad3 Protein KW - Smad3 protein, mouse KW - Trans-Activators KW - Transforming Growth Factor beta KW - Index Medicus KW - Skin -- injuries KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Mice KW - Chemotaxis KW - Mice, Knockout KW - Keratinocytes -- physiology KW - Transforming Growth Factor beta -- physiology KW - Monocytes -- physiology KW - Monocytes -- cytology KW - Cells, Cultured KW - Keratinocytes -- cytology KW - Gene Expression Regulation KW - Bone Marrow Cells -- cytology KW - Transforming Growth Factor beta -- genetics KW - Signal Transduction KW - Bone Marrow Cells -- physiology KW - Male KW - Cell Adhesion KW - Cell Division KW - Wounds and Injuries -- physiopathology KW - Inflammation -- physiopathology KW - Trans-Activators -- deficiency KW - Wounds and Injuries -- pathology KW - Wounds and Injuries -- genetics KW - DNA-Binding Proteins -- genetics KW - Wound Healing -- genetics KW - Inflammation -- genetics KW - Wound Healing -- physiology KW - DNA-Binding Proteins -- deficiency KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- physiology KW - Trans-Activators -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69282184?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+cell+biology&rft.atitle=Mice+lacking+Smad3+show+accelerated+wound+healing+and+an+impaired+local+inflammatory+response.&rft.au=Ashcroft%2C+G+S%3BYang%2C+X%3BGlick%2C+A+B%3BWeinstein%2C+M%3BLetterio%2C+J+L%3BMizel%2C+D+E%3BAnzano%2C+M%3BGreenwell-Wild%2C+T%3BWahl%2C+S+M%3BDeng%2C+C%3BRoberts%2C+A+B&rft.aulast=Ashcroft&rft.aufirst=G&rft.date=1999-09-01&rft.volume=1&rft.issue=5&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=Nature+cell+biology&rft.issn=14657392&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-06 N1 - Date created - 1999-12-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Nat Cell Biol. 1999 Sep;1(5):E117-9 [10559949] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 tumor suppressor gene mutations in transformed cutaneous T-cell lymphoma: a study of 12 cases. AN - 69240493; 10551408 AB - The transformation of cutaneous T-cell lymphoma (t-CTCL) is an uncommon phenomenon that is associated with histopathologic changes and follows an aggressive course. The factors contributing to this transformation are poorly understood. The aim of this study was to analyze the p53 status in t-CTCL and to correlate it with disease outcome. The p53 status was investigated by immunohistochemistry, single-strand conformation polymorphism (SSCP) and DNA sequencing in 12 patients with t-CTCL. Eight mutations were detected; including four in exon 5, one in exon 6 and three in exon 7. Five were point mutations and three were deletions. Paired samples from nontransformed patch and plaque lesions showed no p53 over-expression. Eight disease-related deaths were reported, six to 23 months after transformation, all of which had p53 mutations. Three other patients with wild phenotype (WT-p53) were last reported alive with the disease 19-33 months after transformation (p < 0.0002). One other case had a p53 mutation but a short period of follow-up. Our results suggest that phenotypic changes of t-CTCL are frequently associated with genotype alterations in the p53 gene. Because 70% of the mutations detected were either G to C transversions or deletions, nucleotide-pairing mismatch and not DNA damage by UVB represents a likely mechanism for mutagenesis. Furthermore, the data may help in the design of gene transfer therapies that target the p53 molecule. JF - Journal of cutaneous pathology AU - Marrogi, A J AU - Khan, M A AU - Vonderheid, E C AU - Wood, G S AU - McBurney, E AD - Department of Surgery, LSU School of Medicine, New Orleans, Louisiana, USA. Marrogia@mail.nih.gov Y1 - 1999/09// PY - 1999 DA - September 1999 SP - 369 EP - 378 VL - 26 IS - 8 SN - 0303-6987, 0303-6987 KW - DNA, Neoplasm KW - 0 KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Molecular Structure KW - Models, Molecular KW - Humans KW - Aged KW - DNA, Neoplasm -- analysis KW - Sequence Analysis, DNA KW - Polymorphism, Single-Stranded Conformational KW - Child, Preschool KW - Polymerase Chain Reaction KW - Tumor Suppressor Protein p53 -- analysis KW - Survival Rate KW - Aged, 80 and over KW - Adult KW - Middle Aged KW - Mutation KW - Female KW - Immunoenzyme Techniques KW - Male KW - Skin Neoplasms -- genetics KW - Lymphoma, T-Cell, Cutaneous -- mortality KW - Cell Transformation, Neoplastic -- pathology KW - Genes, p53 KW - Cell Transformation, Neoplastic -- chemistry KW - Lymphoma, T-Cell, Cutaneous -- genetics KW - Skin Neoplasms -- pathology KW - Lymphoma, T-Cell, Cutaneous -- chemistry KW - Skin Neoplasms -- chemistry KW - Lymphoma, T-Cell, Cutaneous -- pathology KW - Cell Transformation, Neoplastic -- genetics KW - Skin Neoplasms -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69240493?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cutaneous+pathology&rft.atitle=p53+tumor+suppressor+gene+mutations+in+transformed+cutaneous+T-cell+lymphoma%3A+a+study+of+12+cases.&rft.au=Marrogi%2C+A+J%3BKhan%2C+M+A%3BVonderheid%2C+E+C%3BWood%2C+G+S%3BMcBurney%2C+E&rft.aulast=Marrogi&rft.aufirst=A&rft.date=1999-09-01&rft.volume=26&rft.issue=8&rft.spage=369&rft.isbn=&rft.btitle=&rft.title=Journal+of+cutaneous+pathology&rft.issn=03036987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-18 N1 - Date created - 1999-11-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine induces cell death, lipid peroxidation and DNA base damage in a catecholaminergic cell line derived from the central nervous system AN - 20150965; 10262818 AB - Dopamine can be autoxidized to superoxides and quinones. Superoxides can form hydroxyl radicals that are highly reactive with lipids, proteins and DNA leading to neuronal damage and cell death. We used a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system to evaluate the effects of dopamine on cell death, lipid peroxidation and DNA base damage. Dopamine produces cell death in CATH.a cells and this is associated with an increase in annexin binding, which is an early indicator of apoptosis. Incubation of CATH.a cells with deferoximine, an iron chealator, partially antagonizes dopamineinduced cell death. In CATH.a cells, dopamine produces an increase in both lipid peroxidation, as measured bycis-parinaric acid fluorescence, and DNA oxidative base damage, as measured by 8-hydroxy-2'-deoxyguanosine formation. Cell death was inhibited 84--92% by the hydrophilic antioxidants, dithiothreitol, L-cysteine, and N-acetylcysteine. The lipophilic vitamins, retinol and vitamin E and the vitamin E analog, Trolox, inhibited dopamine-induced cell death by 18--33%. The lipophilic antioxidants probucol, propyl glycol and butylated hydroxyanisone had no inhibitory effect on dopamine-induced cell death. These data suggest that damage to DNA and lipids may be partially responsible for dopamine-induced cell death in CATH.a cells. JF - Neurotoxicity Research AU - Masserano, Joseph M AU - Baker, Ivory AU - Venable, Diane AU - Gong, Li AU - Zullo, Steven J AU - Merril, Carl R AU - Wyatt, Richard Jed AD - Neuropsychiatry Branch, National Institute of Mental Health, 15 North Drive, MSC 2668, Building 15-K, Room 201, 20892-2668 Bethesda, MD, USA, MASSERAJ@intra.nimh.nih.gov Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 171 EP - 179 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 1 IS - 3 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; CSA Neurosciences Abstracts KW - Central nervous system KW - Apoptosis KW - Fluorescence KW - Antioxidants KW - Data processing KW - Free radicals KW - Lipophilic KW - Lipid peroxidation KW - DNA damage KW - Vitamin E KW - Dopamine KW - Annexins KW - Superoxide KW - Vitamin A KW - Neurotoxicity KW - Quinone KW - DNA KW - Acetylcysteine KW - Dithiothreitol KW - Iron KW - N 14840:Antisense, Nucleotide Analogs KW - N3 11028:Neuropharmacology & toxicology KW - X 24360:Metals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20150965?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Dopamine+induces+cell+death%2C+lipid+peroxidation+and+DNA+base+damage+in+a+catecholaminergic+cell+line+derived+from+the+central+nervous+system&rft.au=Masserano%2C+Joseph+M%3BBaker%2C+Ivory%3BVenable%2C+Diane%3BGong%2C+Li%3BZullo%2C+Steven+J%3BMerril%2C+Carl+R%3BWyatt%2C+Richard+Jed&rft.aulast=Masserano&rft.aufirst=Joseph&rft.date=1999-09-01&rft.volume=1&rft.issue=3&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033288 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - Central nervous system; Data processing; Antioxidants; Fluorescence; Apoptosis; Free radicals; Lipid peroxidation; Lipophilic; DNA damage; Vitamin E; Dopamine; Annexins; Vitamin A; Superoxide; Quinone; Neurotoxicity; DNA; Acetylcysteine; Dithiothreitol; Iron DO - http://dx.doi.org/10.1007/BF03033288 ER - TY - JOUR T1 - RESPONSE: Re: Relationship Between p53 Mutations and Inducible Nitric Oxide Synthase Expression in Human Colorectal Cancer. AN - 1859309443; 10469758 JF - Journal of the National Cancer Institute AU - Ambs AU - Harris AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD. Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 1510 EP - 1511 VL - 91 IS - 17 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859309443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=RESPONSE%3A+Re%3A+Relationship+Between+p53+Mutations+and+Inducible+Nitric+Oxide+Synthase+Expression+in+Human+Colorectal+Cancer.&rft.au=Ambs%3BHarris&rft.aulast=Ambs&rft.aufirst=&rft.date=1999-09-01&rft.volume=91&rft.issue=17&rft.spage=1510&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=1460-2105&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1999-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronicity of Maternal Depressive Symptoms, Maternal Sensitivity, and Child Functioning at 36 Months AN - 1791715122 JF - Developmental Psychology Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 1297 CY - Washington PB - American Psychological Association VL - 35 IS - 5 SN - 0012-1649 KW - Psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1791715122?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apio&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+Psychology&rft.atitle=Chronicity+of+Maternal+Depressive+Symptoms%2C+Maternal+Sensitivity%2C+and+Child+Functioning+at+36+Months&rft.au=&rft.aulast=&rft.aufirst=&rft.date=1999-09-01&rft.volume=35&rft.issue=5&rft.spage=1297&rft.isbn=&rft.btitle=&rft.title=Developmental+Psychology&rft.issn=00121649&rft_id=info:doi/ DB - Periodicals Index Online N1 - Last updated - 2016-05-27 ER - TY - CONF T1 - Role of gene knockout mice in understanding the mechanisms of chemical toxicity and carcinogenesis AN - 17559757; 4738363 AB - Most chemical carcinogens require metabolic activation to electrophilic metabolites that are capable of binding to DNA and causing gene mutation. Carcinogen metabolism is carried out by large groups of xenobiotic-metabolizing enzymes that include the phase I cytochromes P450 (P450) and phase II enzymes that include various transferases. During the past 10 years, considerable attention has been focused on the role of P450s in human cancer susceptibility. Polymorphisms in expression of P450s and transferases exist in humans and these might render increased susceptibility or resistance to cancer. Thus it is important to understanding how P450s participate in the carcinogenesis process and to determine if they are indeed the rate limiting and critical interface between the chemical and its biological activity. Since there are marked species differences in expressions and catalytic activities of the multiple P450 forms that activate carcinogens, this validation process becomes especially difficult. To address the role of P450s in whole animal carcinogenesis, mice were produced that lack the P450s known to catalyze carcinogen activation. Mouse lines having disruption of genes encoding P450s CYP1A2, CYP2E1, and CYP1B1 were developed by use of gene disruption in empbryonic stem cells. Mice lacking expression of microsomal epoxide hydrolase and NADPH:quinone oxidoreductase were also made. These mice exhibit no grossly abnormal phenotypes, suggesting that the xenobiotic-metabolizing enzymes have no critical roles in mammalian development and physiological homeostasis. This explains the occurrence of polymorphisms in humans and other mammalian species. However, these null mice do show differences in sensitivities to acute chemical toxicities, thus establishing the importance of xenobiotic metabolism in activation pathways that lead to cell death. Rodent bioassays using null mice and known genotoxic carcinogens should establish whether these enzymes are required for carcinogenesis in an intact animal model. These studies will also provide a framework for the production of transgenic mice and carcinogen bioassay protocols that may be more predictive for identifying human carcinogens and validate the molecular epidemiology studies ongoing in humans that seek to establish a role for polymorphisms in cancer risk. JF - Cancer Letters AU - Gonzalez, F J AU - Kimura, S Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 199 EP - 204 PB - Elsevier, [URL:http://www.elsevier.com/inca/publications/store/5/0/6/0/5/0/] VL - 143 IS - 2 KW - mechanism KW - knockout mice KW - Toxicology Abstracts KW - Genes KW - Carcinogenesis KW - Cytochrome P450 KW - Xenobiotics KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17559757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Letters&rft.atitle=Role+of+gene+knockout+mice+in+understanding+the+mechanisms+of+chemical+toxicity+and+carcinogenesis&rft.au=Gonzalez%2C+F+J%3BKimura%2C+S&rft.aulast=Gonzalez&rft.aufirst=F&rft.date=1999-09-01&rft.volume=143&rft.issue=2&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/10.1016%2FS0304-3835%2899%2900125-1 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0304-3835(99)00125-1 ER - TY - CONF T1 - Mammary gland carcinogenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in rats: possible mechanisms AN - 17559240; 4738365 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) is a heterocyclic amine derived from cooked meat. Mammary gland cancer can be induced in female Sprague-Dawley rats by administration of several oral doses of PhIP. The mechanism of mammary gland carcinogenesis by PhIP in this rat model is not fully understood but appears to involve several factors. One factor is the formation of PhIP-DNA adducts in the mammary gland after metabolic activation of PhIP. Possible target cell populations include the epithelial cells of the mammary gland terminal end buds (TEBs), putative sites of origin of carcinomas. Another factor involved in the mammary carcinogenicity of PhIP may be an increased proliferation in epithelial cells of the TEBs which occurs after a carcinogenic dose of PhIP is administered. This proliferation would be likely to enhance the fixation of mutations from PhIP-DNA adducts in target cells and facilitate the initiation of carcinogenesis. PhIP exposure also transiently inhibits the development of the mammary gland by retarding the differentiation of TEBs to alveolar buds and lobules. As a consequence, more TEBs are available for neoplastic transformation. Recent studies in rats have also shown that PhIP increases the levels of serum prolactin, a well-recognized promoter of mammary gland cancer, which may further explain the targeting of PhIP to the mammary gland. The results to date indicate that PhIP has multiple effects on the mammary gland and hormone status in rats that could potentially play a role in its ability to induce mammary gland cancer. JF - Cancer Letters AU - Snyderwine, E G Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 211 EP - 215 PB - Elsevier, [URL:http://www.elsevier.com/inca/publications/store/5/0/6/0/5/0/] VL - 143 IS - 2 KW - rats KW - mechanism KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - Toxicology Abstracts KW - Meat KW - Mammary gland KW - Food KW - Carcinogenesis KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17559240?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Letters&rft.atitle=Mammary+gland+carcinogenesis+by+2-amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5D+pyridine+in+rats%3A+possible+mechanisms&rft.au=Snyderwine%2C+E+G&rft.aulast=Snyderwine&rft.aufirst=E&rft.date=1999-09-01&rft.volume=143&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/10.1016%2FS0304-3835%2899%2900127-5 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0304-3835(99)00127-5 ER - TY - CONF T1 - Role of well-done, grilled red meat, heterocyclic amines (HCAs) in the etiology of human cancer AN - 17558348; 4738361 AB - High-temperature cooking techniques and doneness level of red meat are linked to cancer of various sites, particularly colorectal cancer. In a colorectal adenoma study, we found an elevated risk for red meat consumption that was mainly due to an association with well-done/very well-done red meat. High-temperature cooking methods (i.e. grilling) were also associated with increased risk. We are currently using an HCA database linked to this questionnaire to estimate MeIQx, DiMeIQx and PhIP consumption and determine their association with risk of colorectal adenoma. Similar results on red meat doneness and fried meat were found in a case-control study of lung cancer. Thus, initial positive findings are stimulating the development of a more refined questionnaire instrument and its validation using food diaries, 24-h recalls, biomarkers of internal dose and direct food measurements. Furthermore, the use of these exposure assessment approaches are being used in large prospective studies world wide and should help clarify the role of doneness, cooking practices and pyrolysis products in the etiology of human cancer. JF - Cancer Letters AU - Sinha, R AU - Rothman, N Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 189 EP - 194 PB - Elsevier, [URL:http://www.elsevier.com/inca/publications/store/5/0/6/0/5/0/] VL - 143 IS - 2 KW - man KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline KW - Colorectal cancer KW - heterocyclic amines KW - Toxicology Abstracts KW - Meat KW - Food KW - Cooking KW - Cancer KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17558348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Letters&rft.atitle=Role+of+well-done%2C+grilled+red+meat%2C+heterocyclic+amines+%28HCAs%29+in+the+etiology+of+human+cancer&rft.au=Sinha%2C+R%3BRothman%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1999-09-01&rft.volume=143&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Cancer+Letters&rft.issn=03043835&rft_id=info:doi/10.1016%2FS0304-3835%2899%2900123-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1016/S0304-3835(99)00123-8 ER - TY - JOUR T1 - Monitoring cocaine use in substance-abuse-treatment patients by sweat and urine testing AN - 17439284; 4651443 AB - Sweat and urine specimens were collected from 44 methadone-maintenance patients to evaluate the use of sweat testing to monitor cocaine use. Paired sweat patches that were applied and removed weekly (on Tuesdays) were compared with 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays. All patches (N = 930) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay (cutoff concentration 10 ng/mL); a subset of patches (N = 591) was also analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine, benzoylecgonine (BZE), and ecgonine methyl ester (EME) (cutoff concentration 5 ng/mL). Urine specimens were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL) and subsets were analyzed by TDx (semiquantitative, LOD 30 ng/mL) and by GC-MS for cocaine (LOD 5 ng/mL). Results were evaluated to (1) determine the relative amounts of cocaine and its metabolites in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for cocaine in sweat; and (4) compare the detection of cocaine use by sweat and urine testing. Cocaine was detected by GC-MS in 99% of ELISA-positive sweat patches; median concentrations of cocaine, BZE, and EME were 378, 78.7, and 74 ng/mL, respectively. Agreement in duplicate patches was approximately 90% by ELISA analysis. The sensitivity, specificity, and efficiency of sweat ELISA cocaine results as compared with sweat GC-MS results were 93.6%, 91.3%, and 93.2%, respectively. The sensitivity, specificity, and efficiency between ELISA sweat patch and EMIT urine results were 97.6%, 60.5%, and 77.7%, respectively. These results support the use of sweat patches for monitoring cocaine use, though further evaluation is needed. JF - Journal of Analytical Toxicology AU - Preston, K L AU - Huestis, MA AU - Wong, C J AU - Umbricht, A AU - Goldberger, BA AU - Cone, E J AD - National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 313 EP - 322 VL - 23 IS - 5 SN - 0146-4760, 0146-4760 KW - Toxicology Abstracts KW - Gas chromatography KW - Urine KW - Sweat KW - Drug abuse KW - Cocaine KW - Mass spectroscopy KW - X 24222:Analytical procedures KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17439284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Analytical+Toxicology&rft.atitle=Monitoring+cocaine+use+in+substance-abuse-treatment+patients+by+sweat+and+urine+testing&rft.au=Preston%2C+K+L%3BHuestis%2C+MA%3BWong%2C+C+J%3BUmbricht%2C+A%3BGoldberger%2C+BA%3BCone%2C+E+J&rft.aulast=Preston&rft.aufirst=K&rft.date=1999-09-01&rft.volume=23&rft.issue=5&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Journal+of+Analytical+Toxicology&rft.issn=01464760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cocaine; Drug abuse; Urine; Sweat; Gas chromatography; Mass spectroscopy ER - TY - JOUR T1 - Anthrax toxins AN - 17424183; 4648359 AB - Though its lethal effects were ascribed to an exotoxin almost half a century ago, the pathogenesis of anthrax has yet to be satisfactorily explained. Subsequent work has led to the molecular identification and enzymatic characterization of three proteins that constitute two anthrax toxins. Protective antigen binds an as yet unknown cell receptor and mediates the entry of the other two components to the cytoplasm via the endosomal pathway. Edema factor, so named for its ability to induce edema, is a Ca super(2+) /calmodulin-dependent adenylate cyclase. Lethal factor, the dominant virulence factor associated with the toxin, proteolytically inactivates mitogen-activated protein kinase kinases, key players in signal transduction. We describe the fascinating work that has led to these discoveries and discuss their relevance to our understanding of the pathogenesis of anthrax. JF - Cellular and Molecular Life Sciences AU - Duesbery, N S AU - Woude, GFV AD - Division of Basic Sciences, NCI-FCRDC, P.O. Box B, Frederick, (Maryland 21702, USA), woude@ncifcrf.gov Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 1599 EP - 1609 VL - 55 IS - 12 SN - 1420-682X, 1420-682X KW - edema factor KW - lethal factor KW - protective antigen KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Reviews KW - Anthrax KW - Bacillus anthracis KW - Toxins KW - Exotoxins KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17424183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+Molecular+Life+Sciences&rft.atitle=Anthrax+toxins&rft.au=Duesbery%2C+N+S%3BWoude%2C+GFV&rft.aulast=Duesbery&rft.aufirst=N&rft.date=1999-09-01&rft.volume=55&rft.issue=12&rft.spage=1599&rft.isbn=&rft.btitle=&rft.title=Cellular+and+Molecular+Life+Sciences&rft.issn=1420682X&rft_id=info:doi/10.1007%2Fs000180050399 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Exotoxins; Toxins; Reviews; Anthrax DO - http://dx.doi.org/10.1007/s000180050399 ER - TY - JOUR T1 - Comparison of the spectra of genetic damage in formaldehyde-induced ad-3 mutations between DNA repair-proficient and -deficient heterokaryons of Neurospora crassa AN - 17403245; 4626629 AB - The mutagenic effects of formaldehyde (FA) have been compared in DNA repair-proficient (heterokaryon 12) and DNA repair-deficient (heterokaryon 59) two-component heterokaryons of Neurospora crassa. The data from forward-mutation experiments were used to compare the spectra of FA-induced specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region and on the FA-induced inactivation of heterokaryotic conidia. Previous studies have demonstrated that specific-locus mutations at these two loci result from five major genotypic classes, namely two classes of gene/point mutations (ad-3A super(R) and ad-3B super(R)), and three classes of multilocus deletion mutations ([ad-3A] super(IR), [ad-3B] super(IR), and [ad-3A ad-3B] super(IR)). Genetic analysis of ad-3 mutants recovered from both heterokaryons after FA treatment demonstrates that predominantly gene/point mutations were found in H-12 (93.2% ad-3 super(R), 6.8% [ad-3] super(IR)) and a significantly higher frequency of multilocus deletion mutations in H-59 (62.8% ad-3 super(R), 37.0% [ad-3] super(IR)). The data from our experiments with FA on H-12 demonstrate and confirm the data from other assays that FA is a weak mutagen in this DNA repair-proficient strain. However, the data from our experiments with the DNA repair-deficient strain H-59 demonstrate that comparable concentrations of FA cause more pronounced inactivation of heterokaryotic conidia and, at the highest concentration tested, about a 35-fold higher frequency of ad-3 mutations. In addition, FA induced a 5.4-fold higher frequency of ad-3 mutations resulting from multilocus deletion mutation in H-59 than in H-12. Based on our earlier studies with X-ray-induced multilocus deletion mutations, it is this class of FA-induced ad-3 mutations that might be most expected to show deleterious heterozygous effects. The implications of the present data base from our experiments with Neurospora are that the mutagenic (and possibly the carcinogenic) effect of FA exposure might well vary in different human population subgroups. JF - Mutation Research-Reviews in Mutation Research AU - de Serres, FJ AU - Brockman, HE AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Systems Toxicology Branch, Environmental Toxicology Program, National Institute of Environmental Health Sciences Research Triangle Park, NC USA Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 151 EP - 163 PB - Elsevier Science VL - 437 IS - 2 SN - 1383-5742, 1383-5742 KW - ad-3 gene KW - adenine-3 gene KW - formaldehyde KW - Genetics Abstracts; Toxicology Abstracts KW - Heterokaryons KW - DNA damage KW - Neurospora crassa KW - Mutagenicity KW - Formaldehyde KW - DNA repair KW - Mutagenesis KW - X 24155:Biochemistry KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17403245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Comparison+of+the+spectra+of+genetic+damage+in+formaldehyde-induced+ad-3+mutations+between+DNA+repair-proficient+and+-deficient+heterokaryons+of+Neurospora+crassa&rft.au=de+Serres%2C+FJ%3BBrockman%2C+HE&rft.aulast=de+Serres&rft.aufirst=FJ&rft.date=1999-09-01&rft.volume=437&rft.issue=2&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/10.1016%2FS1383-5742%2899%2900081-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neurospora crassa; Formaldehyde; DNA damage; DNA repair; Mutagenicity; Heterokaryons; Mutagenesis DO - http://dx.doi.org/10.1016/S1383-5742(99)00081-2 ER - TY - JOUR T1 - Flicker Image Comparison of 2-D Gel Images for Putative Protein Identification using the 2DWG Meta-Database AN - 17402876; 4631097 AB - With the availability of two-dimensional (2-D) gel electrophoresis databases that have many characterized proteins, it may be possible to compare a researcher's gel images with those in relevant databases. This may lead to the putative identification of unknown protein spots in a researcher's gel with those characterized in a given database, saving the researcher time and money by suggesting monoclonal antibodies to try in confirming these identifications. We have developed two tools to help with this comparison: (1) Flicker, http://www.lecb.ncifcrf.gov/flicker/, a Java applet program running in the researcher's Web browser, to visually compare their gels against gels on the Internet; and (2) the 2DWG meta-database, http://www.lecb.ncifcrf.gov/2dwgDB/, a searchable database of locations of 2-D electrophoretic gel images found on the Internet. Recent I additions to Flicker allow users to click on a protein spot in a gel that is linked to a federated 2D gel database, such as SWISS-2DPAGE, and have it retrieve a report from that Web database for that protein. JF - Molecular Biotechnology AU - Lemkin, P F AU - Thornwall, G AD - IPS/LECB NCI/FCRDC, Frederick, MD 21702, USA, lemkin@ncifcrf.gov Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 159 EP - 172 VL - 12 IS - 2 SN - 1073-6085, 1073-6085 KW - identification KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Databases KW - Monoclonal antibodies KW - Proteins KW - Computer applications KW - Gel electrophoresis KW - W2 32080:Bioinformatics and computer applications KW - W3 33080:Bioinformatics and computer applications KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17402876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Biotechnology&rft.atitle=Flicker+Image+Comparison+of+2-D+Gel+Images+for+Putative+Protein+Identification+using+the+2DWG+Meta-Database&rft.au=Lemkin%2C+P+F%3BThornwall%2C+G&rft.aulast=Lemkin&rft.aufirst=P&rft.date=1999-09-01&rft.volume=12&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Molecular+Biotechnology&rft.issn=10736085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Computer applications; Gel electrophoresis; Databases; Monoclonal antibodies; Proteins ER - TY - JOUR T1 - Rhabdomyosarcoma - working out the pathways AN - 17399496; 4622387 AB - Rhabdomyosarcomas constitute a collection of childhood malignancies thought to arise as a consequence of regulatory disruption of skeletal muscle progenitor cell growth and differentiation. Our understanding of the pathogenesis of this neoplasm has recently benefited from the study of normal and malignant myogenic cells in vitro, facilitating the identification of diagnostic cytogenetic markers and the elucidation of mechanisms by which myogenesis is regulated. It is now appreciated that the delicate balance between proliferation and differentiation, mutually exclusive yet intimately associated processes, is normally controlled in large part through the action of a multitude of growth factors, whose signals are interpreted by members of the MyoD family of helix - loop - helix proteins, and key regulatory cell cycle factors. The latter have proven to be frequent targets of mutational events that subvert myogenesis and promote the development of rhabdomyosarcoma. Although significant progress has been made in the treatment of rhabdomyosarcoma, patients presenting with metastatic disease or certain high risk features are still faced with a dismal prognosis. Only now are genetically engineered mouse models becoming available that are certain to provide fresh insights into the molecular/genetic pathways by which rhabdomyosarcomas arise and progress, and to suggest novel avenues of therapeutic opportunity. JF - Oncogene AU - Merlino, G AU - Helman, L J AD - Molecular Genetics Section, Laboratory of Molecular Biology, National Cancer Institute, N.I.H. Building 37, Room 2E24, Bethesda, Maryland, MD 20892-4255, USA Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 5340 EP - 5348 VL - 18 IS - 38 SN - 0950-9232, 0950-9232 KW - animal models KW - mice KW - man KW - MyoD protein KW - helix-loop-helix proteins KW - rhabdomyosarcoma KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Reviews KW - Cell cycle KW - Skeletal muscle KW - W3 33056:Animal models of human disease KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17399496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Rhabdomyosarcoma+-+working+out+the+pathways&rft.au=Merlino%2C+G%3BHelman%2C+L+J&rft.aulast=Merlino&rft.aufirst=G&rft.date=1999-09-01&rft.volume=18&rft.issue=38&rft.spage=5340&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Mouse Models of Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Skeletal muscle; Cell cycle; Gene therapy ER - TY - JOUR T1 - Development of a flexible and specific gene delivery system for production of murine tumor models AN - 17399468; 4622377 AB - To develop models of human cancer we have expressed the avian retroviral receptor, TVA, under a variety of mammalian promoters in transgenic mice, thus rendering mice susceptible to infection with avian leukosis virus-derived gene vectors. TV A-based retroviral gene transfer offers advantages over current murine models of human cancer. A single transgenic mouse line can be used to evaluate multiple genetic lesions, individually and in combination. Furthermore, mutant genes are introduced somatically into animals, as occurs in the majority of naturally occurring tumors. Because the avian viral vectors replicate only in avian cells, the viral receptor in infected transgenic mouse cells remains available for multiple rounds of infection with different ASLV vectors. We discuss the theoretical and practical aspects of using recombinant avian retroviruses with TVA transgenic mice to generate cancer models. JF - Oncogene AU - Fisher, G H AU - Orsulic, S AU - Holland, E AU - Hively, W P AU - Li, Y AU - Lewis, B C AU - Williams, BO AU - Varmus, HE AD - Varmus Lab, NIH-NCI-DBS, 49 Convent Drive, Building 49, 4A56, Bethesda, Maryland, MD 20892, USA Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 5253 EP - 5260 VL - 18 IS - 38 SN - 0950-9232, 0950-9232 KW - transgenic mice KW - avian leukosis virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Gene transfer KW - Tumors KW - Cancer KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17399468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Development+of+a+flexible+and+specific+gene+delivery+system+for+production+of+murine+tumor+models&rft.au=Fisher%2C+G+H%3BOrsulic%2C+S%3BHolland%2C+E%3BHively%2C+W+P%3BLi%2C+Y%3BLewis%2C+B+C%3BWilliams%2C+BO%3BVarmus%2C+HE&rft.aulast=Fisher&rft.aufirst=G&rft.date=1999-09-01&rft.volume=18&rft.issue=38&rft.spage=5253&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Mouse Models of Cancer. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumors; Gene transfer; Expression vectors; Cancer; Gene therapy ER - TY - JOUR T1 - Temperature and air pollution as risk factors for cerebral vascular diseases in Tokyo for 65+ males and females for July-August, 1980-1995 AN - 17394698; 4617363 AB - Cerebral vascular diseases include cerebral hemorrhage, cerebral infarction and cerebral ischemia. Analysis of the numbers of emergency transport cases/million for these three diseases for July-August, 1980-1995 indicated that 65+ males and females have the highest number of emergency transport cases and the highest frequency of occurrence. Regression models for each disease included maximum daily temperatures, T sub(max), and daily average NO sub(2) and O sub(3) concentrations as model co-variates. Generalized linear models (GLMs) and a generalized estimating equation (GEE) method were used to compute estimates of model parameters. For cerebral hemorrhage, T sub(max) with a lag time of 4 days was the primary risk factor and there was no difference in response between males and females. For cerebral infarction, same day average NO sub(2) concentration was the significant risk factor. The number of emergency transports for cerebral infarction for males was greater than for females. For cerebral ischemia, same day T sub(max) and O sub(3) were the significant risk factors. The number of emergency transports for cerebral ischemia was slightly greater for males than for females. The underlying mechanisms for these observations was not clear but they may be related to greater heat and air quality stress that can adversely affect cardiovascular and respiratory system functions. JF - World Resource Review AU - Piver, W T AU - Ando, M AU - Ye, F AU - Portier, C AD - National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709 USA Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 337 EP - 345 VL - 11 IS - 3 SN - 1042-8011, 1042-8011 KW - Japan, Tokyo KW - cerebrovascular system KW - elderly KW - Risk Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Pollution effects KW - Public health KW - Mortality KW - Temperature KW - Air pollution KW - R2 23060:Medical and environmental health KW - H 12000:Epidemiology and Public Health KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17394698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=World+Resource+Review&rft.atitle=Temperature+and+air+pollution+as+risk+factors+for+cerebral+vascular+diseases+in+Tokyo+for+65%2B+males+and+females+for+July-August%2C+1980-1995&rft.au=Piver%2C+W+T%3BAndo%2C+M%3BYe%2C+F%3BPortier%2C+C&rft.aulast=Piver&rft.aufirst=W&rft.date=1999-09-01&rft.volume=11&rft.issue=3&rft.spage=337&rft.isbn=&rft.btitle=&rft.title=World+Resource+Review&rft.issn=10428011&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Temperature; Air pollution; Pollution effects; Public health; Mortality ER - TY - JOUR T1 - Role of the Sporulation Protein BofA in Regulating Activation of the Bacillus subtilis Developmental Transcription Factor sigma super(K) AN - 17379431; 4596981 AB - During sporulation, the Bacillus subtilis transcription factor sigma super(K) is activated by regulated proteolytic processing. I have used a system that facilitates the analysis of the contributions of a modified form of the processing enzyme, SpoIVFB-GFP and the regulatory proteins BofA and SpoIVFA to the conversion of pro- sigma super(K) to sigma super(K). The results show that in the presence of BofA, SpoIVFA levels increase by greater than 20-fold SpoIVFA is substantially stabilized, and pro- sigma super(K) processing is inhibited. In addition, enhanced accumulation of the SpoIVFA protein in the absence of BofA (achieved through the use of an ftsH null mutation) substantially inhibits pro- sigma super(K) processing. These results suggest that during growth, increased accumulation of the SpoIVFA protein inhibits the activity of SpoIVFB-GFP and regulates the activation of sigma super(K). JF - Journal of Bacteriology AU - Resnekov, O AD - Section on Microbial Genetics, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, Building 6B-304, National Institutes of Health, 6 Center Dr., MSC 2785, Bethesda, MD 20892-2785, resnekov@biosun.harvard.edu Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 5384 EP - 5388 VL - 181 IS - 17 SN - 0021-9193, 0021-9193 KW - BofA protein KW - sigma factor sK KW - Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - Bacillus subtilis KW - Transcription factors KW - Gene regulation KW - Sporulation KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17379431?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Role+of+the+Sporulation+Protein+BofA+in+Regulating+Activation+of+the+Bacillus+subtilis+Developmental+Transcription+Factor+sigma+super%28K%29&rft.au=Resnekov%2C+O&rft.aulast=Resnekov&rft.aufirst=O&rft.date=1999-09-01&rft.volume=181&rft.issue=17&rft.spage=5384&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus subtilis; Gene regulation; Transcription factors; Proteolysis; Sporulation ER - TY - JOUR T1 - Genomic Plasticity in Natural Populations of Bordetella pertussis AN - 17377881; 4597019 AB - We determined the genomic organization of 14 clinical strains of Bordetella pertussis isolated over an 18-month period in Alberta, Canada. The maps of these 14 strains, while demonstrating general similarity of gene order, display a number of examples of genomic rearrangements in the form of large chromosomal inversions. JF - Journal of Bacteriology AU - Stibitz, S AU - Yang, M AD - Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, stibitz@helix.nih.gov Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 5512 EP - 5515 VL - 181 IS - 17 SN - 0021-9193, 0021-9193 KW - Canada, Alberta KW - Microbiology Abstracts B: Bacteriology KW - Genomes KW - Bordetella pertussis KW - Genetic mapping KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17377881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Genomic+Plasticity+in+Natural+Populations+of+Bordetella+pertussis&rft.au=Stibitz%2C+S%3BYang%2C+M&rft.aulast=Stibitz&rft.aufirst=S&rft.date=1999-09-01&rft.volume=181&rft.issue=17&rft.spage=5512&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bordetella pertussis; Genetic mapping; Genomes ER - TY - JOUR T1 - Retroviral Transfer of Human MDR1 Gene to Hematopoietic Cells: Effects of Drug Selection and of Transcript Splicing on Expression of Encoded P-Glycoprotein AN - 17341822; 4611507 AB - Protection of hematopoietic cells of patients undergoing anticancer chemotherapy by MDR1 gene transfer is currently being studied in clinical trials. From animal studies, it has been suggested that aberrant splicing due to cryptic donor and acceptor sites in the MDR1 cDNA could be a major reason for failure to obtain high-level expression of P-glycoprotein in bone marrow. We investigated effects of drug selection on protein expression levels and on splicing of MDR1 transcripts in murine bone marrow cells (BMCs) in vitro. To this end, retroviruses were generated through an identical plasmid, pHaMDR1/A, introduced into different packaging cells. GP + E86- but not PA317-derived producer cells were found to express truncated in addition to full-length message. In BMCs transduced with GP + E86-derived viruses, both messages were increased after treatment with colchicine or daunomycin. Similar results were obtained with NIH 3T3 fibroblasts. However, transduced and drug-selected BMCs displayed the spliced transcript even if the respective PA317-derived producer cells contained no truncated RNA as detected in transduced NIH 3T3 fibroblasts. Short-term drug selection in BMCs transduced with either ecotropic or amphotropic retroviruses resulted in a striking increase in P-glycoprotein expression. Thus, aberrant splicing failed to abrogate P-glycoprotein expression in BMCs. We also studied a vector in which MDR1 was coexpressed with glucocerebrosidase, using an internal ribosomal entry site. Although chemoprotection was less efficient than with pHaMDR1/A, augmentation of protein expression was observed at low selecting drug concentrations. Our study shows that drug selection can partially compensate for inefficient transduction of hematopoietic cells, and may help to develop strategies by which unstable expression of transduced genes can be overcome. JF - Human Gene Therapy AU - Licht, T AU - Aran, J M AU - Goldenberg, S K AU - Vieira, W D AU - Gottesman, M M AU - Pastan, IRA AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA, pasta@helix.nih.gov Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 2173 EP - 2185 VL - 10 IS - 13 SN - 1043-0342, 1043-0342 KW - MDR1 gene KW - Mdr1 gene KW - P-glycoprotein KW - glucocerebrosidase KW - man KW - mice KW - plasmid pHaMDR1/A KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Bone marrow KW - Daunomycin KW - Splicing KW - Gene transfer KW - Colchicine KW - Drugs KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17341822?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+Transfer+of+Human+MDR1+Gene+to+Hematopoietic+Cells%3A+Effects+of+Drug+Selection+and+of+Transcript+Splicing+on+Expression+of+Encoded+P-Glycoprotein&rft.au=Licht%2C+T%3BAran%2C+J+M%3BGoldenberg%2C+S+K%3BVieira%2C+W+D%3BGottesman%2C+M+M%3BPastan%2C+IRA&rft.aulast=Licht&rft.aufirst=T&rft.date=1999-09-01&rft.volume=10&rft.issue=13&rft.spage=2173&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950017167 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Daunomycin; Splicing; Drugs; Gene transfer; Colchicine; Bone marrow DO - http://dx.doi.org/10.1089/10430349950017167 ER - TY - JOUR T1 - Strand opening by the UvrA sub(2)B complex allows dynamic recognition of DNA damage AN - 17341570; 4619938 AB - Repair proteins alter the local DNA structure during nucleotide excision repair (NER). However, the precise role of DNA melting remains unknown. A series of DNA substrates containing a unique site- specific BPDE-guanine adduct in a region of non- complementary bases were examined for incision by the Escherichia coli UvrBC endonuclease in the presence or absence of UvrA. UvrBC formed a pre- incision intermediate with a DNA substrate containing a 6-base bubble structure with 2 unpaired bases 5' and 3 unpaired bases 3' to the adduct. Formation of this bubble served as a dynamic recognition step in damage processing. UvrB or UvrBC may form one of three stable repair intermediates with DNA substrates, depending upon the state of the DNA surrounding the modified base. The dual incisions were strongly determined by the distance between the adduct and the double- stranded-single-stranded DNA junction of the bubble, and required homologous double-stranded DNA at both incision sites. Remarkably, in the absence of UvrA, UvrBC nuclease can make both 3' and 5' incisions on substrates with bubbles of 3-6 nucleotides, and an uncoupled 5' incision on bubbles of greater than or equal to greater than or equal to 10 nucleotides. These data support the hypothesis that the E.coli and human NER systems recognize and process DNA damage in a highly conserved manner. JF - EMBO Journal AU - Zou, Y AU - Van Houten, B AD - Sealy Center for Molecular Science and Department of Human Biological Chemistry & Genetics, University of Texas Medical Branch, Galveston, TX 77555, USA, vanhout1@niehs.nih.gov Y1 - 1999/09/01/ PY - 1999 DA - 1999 Sep 01 SP - 4889 EP - 4901 VL - 18 IS - 17 SN - 0261-4189, 0261-4189 KW - UvrA protein KW - UvrB protein KW - UvrC protein KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA adducts KW - DNA repair KW - DNA damage KW - Nucleotide excision repair KW - Escherichia coli KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24240:Miscellaneous KW - N 14712:DNases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17341570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Strand+opening+by+the+UvrA+sub%282%29B+complex+allows+dynamic+recognition+of+DNA+damage&rft.au=Zou%2C+Y%3BVan+Houten%2C+B&rft.aulast=Zou&rft.aufirst=Y&rft.date=1999-09-01&rft.volume=18&rft.issue=17&rft.spage=4889&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA repair; DNA damage; Nucleotide excision repair; DNA adducts ER - TY - JOUR T1 - Sulfated polysaccharide-directed recruitment of mammalian host proteins: A novel strategy in microbial pathogenesis AN - 17321938; 4601529 AB - Fundamental to the virulence of microbial pathogens is their capacity for adaptation and survival within variable, and often hostile, environments encountered in the host. We describe a novel, extragenomic mechanism of surface modulation which may amplify the adaptive and pathogenic potential of numerous bacterial species, including Staphylococcus, Yersinia, and pathogenic Neisseria species, as well as Helicobacter pylori and Streptococcus pyogenes. The mechanism involves specific bacterial recruitment of heparin, glycosaminoglycans, or related sulfated polysaccharides, which in turn serve as universal binding sites for a diverse array of mammalian heparin binding proteins, including adhesive glycoproteins (vitronectin and fibronectin), inflammatory (MCP-3, PF-4, and MIP-1 alpha ) and immunomodulatory (gamma interferon) intermediates, and fibro-blast growth factor. This strategy impacts key aspects of microbial pathogenicity as exemplified by increased bacterial invasion of epithelial cells and inhibition of chemokine-induced chemotaxis. Our findings illustrate a previously unrecognized form of parasitism that complements classical virulence strategies encoded within the microbial genome. JF - Infection and Immunity AU - Duensing, ThD AU - Wing, J S AU - Van Putten, JPM AD - Rocky Mountain Laboratories, 903 South Fourth St., Hamilton, MT 59840, USA, jos_van_putten@nih.gov Y1 - 1999/09// PY - 1999 DA - Sep 1999 SP - 4463 EP - 4468 VL - 67 IS - 9 SN - 0019-9567, 0019-9567 KW - Glycosaminoglycans KW - Vitronectin KW - Microbiology Abstracts B: Bacteriology KW - Helicobacter pylori KW - Neisseria KW - Fibronectin KW - Staphylococcus KW - Chemotaxis KW - Parasitism KW - Yersinia KW - Streptococcus pyogenes KW - Fibroblasts KW - Virulence KW - Growth factors KW - Heparin KW - J 02730:Carbohydrates UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17321938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Sulfated+polysaccharide-directed+recruitment+of+mammalian+host+proteins%3A+A+novel+strategy+in+microbial+pathogenesis&rft.au=Duensing%2C+ThD%3BWing%2C+J+S%3BVan+Putten%2C+JPM&rft.aulast=Duensing&rft.aufirst=ThD&rft.date=1999-09-01&rft.volume=67&rft.issue=9&rft.spage=4463&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Neisseria; Staphylococcus; Streptococcus pyogenes; Yersinia; Growth factors; Virulence; Heparin; Parasitism; Chemotaxis; Fibronectin; Fibroblasts ER - TY - JOUR T1 - Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice. AN - 70019515; 10468635 AB - Muscarinic acetylcholine receptors (M(1)-M(5)) regulate many key functions of the central and peripheral nervous system. Primarily because of the lack of receptor subtype-selective ligands, the precise physiological roles of the individual muscarinic receptor subtypes remain to be elucidated. Interestingly, the M(4) receptor subtype is expressed abundantly in the striatum and various other forebrain regions. To study its potential role in the regulation of locomotor activity and other central functions, we used gene-targeting technology to create mice that lack functional M(4) receptors. Pharmacologic analysis of M(4) receptor-deficient mice indicated that M(4) receptors are not required for muscarinic receptor-mediated analgesia, tremor, hypothermia, and salivation. Strikingly, M(4) receptor-deficient mice showed an increase in basal locomotor activity and greatly enhanced locomotor responses (as compared with their wild-type littermates) after activation of D1 dopamine receptors. These results indicate that M(4) receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels. Our findings offer new perspectives for the treatment of Parkinson's disease and other movement disorders that are characterized by an imbalance between muscarinic cholinergic and dopaminergic neurotransmission. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gomeza, J AU - Zhang, L AU - Kostenis, E AU - Felder, C AU - Bymaster, F AU - Brodkin, J AU - Shannon, H AU - Xia, B AU - Deng, C AU - Wess, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Y1 - 1999/08/31/ PY - 1999 DA - 1999 Aug 31 SP - 10483 EP - 10488 VL - 96 IS - 18 SN - 0027-8424, 0027-8424 KW - Dopamine Agonists KW - 0 KW - Receptor, Muscarinic M4 KW - Receptors, Dopamine D1 KW - Receptors, Muscarinic KW - Quinpirole KW - 20OP60125T KW - Oxotremorine KW - 5RY0UWH1JL KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Tremor -- physiopathology KW - Animals KW - Salivation -- drug effects KW - Apomorphine -- pharmacology KW - Mice KW - Radioligand Assay KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology KW - Tremor -- chemically induced KW - Mice, Knockout KW - Analgesia KW - Quinpirole -- pharmacology KW - Corpus Striatum -- physiology KW - Hypothermia -- physiopathology KW - Dopamine Agonists -- pharmacology KW - Prosencephalon -- physiology KW - Receptors, Muscarinic -- genetics KW - Oxotremorine -- pharmacology KW - Receptors, Dopamine D1 -- physiology KW - Motor Activity -- physiology KW - Motor Activity -- drug effects KW - Receptors, Muscarinic -- physiology KW - Brain -- physiology KW - Receptors, Muscarinic -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70019515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Enhancement+of+D1+dopamine+receptor-mediated+locomotor+stimulation+in+M%284%29+muscarinic+acetylcholine+receptor+knockout+mice.&rft.au=Gomeza%2C+J%3BZhang%2C+L%3BKostenis%2C+E%3BFelder%2C+C%3BBymaster%2C+F%3BBrodkin%2C+J%3BShannon%2C+H%3BXia%2C+B%3BDeng%2C+C%3BWess%2C+J&rft.aulast=Gomeza&rft.aufirst=J&rft.date=1999-08-31&rft.volume=96&rft.issue=18&rft.spage=10483&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-07 N1 - Date created - 1999-10-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1990 Dec 7;250(4986):1429-32 [2147780] J Pharmacol Exp Ther. 1991 Feb;256(2):727-33 [1994002] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4205-9 [1827915] J Neurosci. 1991 Oct;11(10):3218-26 [1941081] Psychopharmacology (Berl). 1991;105(3):335-9 [1839178] Trends Pharmacol Sci. 1992 Feb;13(2):61-9 [1561715] J Neurochem. 1992 Jul;59(1):245-51 [1319468] J Neurosci. 1992 Sep;12(9):3591-600 [1527598] Mol Pharmacol. 1993 Feb;43(2):149-57 [8429821] Eur J Pharmacol. 1985 Oct 29;117(1):81-8 [3841316] Prog Neurobiol. 1986;26(2):119-46 [3704168] Neuropharmacology. 1986 May;25(5):455-63 [3488514] Proc Natl Acad Sci U S A. 1990 Jan;87(1):230-4 [2296581] Trends Pharmacol Sci. 1989 Dec;Suppl:75-9 [2694528] Proc Natl Acad Sci U S A. 1990 Sep;87(18):7050-4 [2402490] Life Sci. 1993;52(5-6):441-8 [8441326] J Pharmacol Exp Ther. 1993 Jul;266(1):329-38 [8101218] Pharmacol Ther. 1993 Jun;58(3):319-79 [7504306] Prog Brain Res. 1993;98:95-101 [8248542] J Neurosci. 1994 May;14(5 Pt 2):3351-63 [8182478] Trends Neurosci. 1994 Jun;17(6):228-33 [7521083] Cell. 1994 Nov 18;79(4):729-42 [7954836] Ann N Y Acad Sci. 1995 May 10;757:186-93 [7611674] J Neurochem. 1995 Sep;65(3):1124-30 [7643090] Nat Genet. 1995 Sep;11(1):33-9 [7550311] J Neurosci. 1995 Dec;15(12):8167-76 [8613751] Cell. 1996 Mar 22;84(6):911-21 [8601314] Trends Neurosci. 1996 May;19(5):177-81 [8723200] Br J Pharmacol. 1996 May;118(2):283-8 [8735628] Br J Pharmacol. 1996 Jun;118(4):827-8 [8799550] Crit Rev Neurobiol. 1996;10(1):69-99 [8853955] Life Sci. 1997;60(13-14):969-76 [9121363] J Pharmacol Exp Ther. 1997 May;281(2):876-83 [9152397] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13311-6 [9371842] J Neurosci. 1998 May 1;18(9):3470-9 [9547254] Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1692-7 [9990086] J Pharmacol Exp Ther. 1999 Mar;288(3):1143-50 [10027852] Comment In: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12222-3 [10535900] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The beta-globin promoter is important for recruitment of erythroid Krüppel-like factor to the locus control region in erythroid cells. AN - 70003536; 10468560 AB - Erythroid Krüppel-like factor (EKLF), which binds to the CACCC box in the beta-globin promoter, is required for the expression of the beta-globin gene in adult erythroid cells. It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region (LCR) 5'HS3. Some evidence suggests that the LCR and the beta-globin promoter interact in adult erythroid cells, and the network of protein-protein interactions that exists between these two elements may regulate how EKLF is recruited to the LCR. In this report, we use the PIN*POINT assay to study the role of the promoter on the recruitment of EKLF to 5'HS2 and 5'HS3 of the LCR. We find that recruitment of EKLF to 5'HS2 requires the TATA box, but recruitment to 5'HS3 depends on the CACCC and TATA boxes of the beta-globin promoter. Furthermore, recruitment of EKLF to 5'HS3 only occurred in beta-globin-expressing murine erythroid leukemia cells, whereas recruitment of EKLF to 5'HS2 occurred in both gamma-globin-expressing K562 cells and murine erythroid leukemia cells. Unlike EKLF, Sp1, which also binds to CACCC boxes, is not recruited to 5'HS3. We have also examined how one 5'HS affects the recruitment of EKLF to another 5'HS. We have found that the recruitment of EKLF to 5'HS3 depends on the presence of 5'HS2 in cis, but the recruitment to 5'HS2 does not depend on 5'HS3. Based on these results, we present a model that illustrates how EKLF may be recruited to the beta-globin locus. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Lee, J S AU - Lee, C H AU - Chung, J H AD - Molecular Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/08/31/ PY - 1999 DA - 1999 Aug 31 SP - 10051 EP - 10055 VL - 96 IS - 18 SN - 0027-8424, 0027-8424 KW - Codon KW - 0 KW - DNA-Binding Proteins KW - Kruppel-Like Transcription Factors KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Transcription Factors KW - erythroid Kruppel-like factor KW - Globins KW - 9004-22-2 KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - Humans KW - Mice KW - K562 Cells KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Leukemia, Experimental KW - Tumor Cells, Cultured KW - Transfection KW - Introns KW - Molecular Sequence Data KW - Zinc Fingers KW - TATA Box KW - Phosphoproteins -- metabolism KW - Promoter Regions, Genetic KW - Transcription Factors -- metabolism KW - Locus Control Region KW - Globins -- genetics KW - Erythrocytes -- metabolism KW - Globins -- biosynthesis KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70003536?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+beta-globin+promoter+is+important+for+recruitment+of+erythroid+Kr%C3%BCppel-like+factor+to+the+locus+control+region+in+erythroid+cells.&rft.au=Lee%2C+J+S%3BLee%2C+C+H%3BChung%2C+J+H&rft.aulast=Lee&rft.aufirst=J&rft.date=1999-08-31&rft.volume=96&rft.issue=18&rft.spage=10051&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-07 N1 - Date created - 1999-10-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1995 Jan 27;270(4):1955-9 [7829533] Philos Trans R Soc Lond B Biol Sci. 1996 Apr 29;351(1339):491-9 [8735271] Curr Opin Genet Dev. 1996 Aug;6(4):488-95 [8791532] Cell. 1996 Oct 4;87(1):105-14 [8858153] Dev Dyn. 1996 Jul;206(3):248-59 [8896981] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12267-71 [8901569] EMBO J. 1996 Nov 1;15(21):5888-96 [8918466] Genes Dev. 1996 Nov 15;10(22):2894-902 [8918890] Development. 1996 Dec;122(12):3991-9 [9012519] Cell. 1997 Oct 3;91(1):13-5 [9335330] Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):969-74 [9448269] Mol Cell Biol. 1998 Jul;18(7):4188-96 [9632803] Ann N Y Acad Sci. 1998 Jun 30;850:45-53 [9668526] Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60 [9707565] Genes Dev. 1998 Sep 15;12(18):2863-73 [9744863] Genes Cells. 1998 Jul;3(7):415-29 [9753424] Cell. 1998 Oct 2;95(1):93-104 [9778250] Mol Cell. 1998 Oct;2(4):447-55 [9809066] Mol Cell Biol. 1999 Apr;19(4):3062-72 [10082573] Cell. 1987 Dec 24;51(6):1079-90 [3319186] Proc Natl Acad Sci U S A. 1989 Apr;86(8):2554-8 [2704733] EMBO J. 1990 Jan;9(1):233-40 [2295312] EMBO J. 1990 Jul;9(7):2169-77 [2357965] Genes Dev. 1990 Oct;4(10):1637-49 [2249769] Blood. 1991 May 15;77(10):2272-84 [1709381] Genes Dev. 1991 Aug;5(8):1387-94 [1714415] Mol Cell Biol. 1993 May;13(5):2776-86 [7682653] Mol Cell Biol. 1993 Jul;13(7):3990-8 [8321206] Nucleic Acids Res. 1994 Mar 25;22(6):1006-11 [8152905] Cell. 1994 Apr 8;77(1):5-8 [8156597] Mol Cell Biol. 1995 Feb;15(2):852-60 [7823951] Nature. 1995 May 25;375(6529):318-22 [7753195] Eur J Biochem. 1995 Jul 15;231(2):271-81 [7635138] Nature. 1995 Sep 21;377(6546):209-13 [7675106] Genes Dev. 1995 Sep 15;9(18):2203-13 [7557375] Genes Dev. 1995 Dec 15;9(24):3083-96 [8543153] Cell. 1996 Jan 26;84(2):179-82 [8565061] J Biol Chem. 1996 May 17;271(20):11871-8 [8662652] Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6605-9 [8692864] Nature. 1995 May 25;375(6529):316-8 [7753194] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A physiological model for ligand-induced accumulation of alpha sub(2u) globulin in male rat kidney. Roles of protein synthesis and lysosomal degradation in the renal dosimetry of 2,4,4-trimethyl-2-pentanol AN - 17402114; 4627645 AB - A physiologically based pharmacokinetic (PBPK) model was constructed for the disposition of 2,4,4-trimethyl-2-pentanol (TMP-2-OH) in male rats and its induction of accumulation of renal alpha sub(2u)-globulin ( alpha 2u). The model included diffusion-restricted delivery of TMP-2-OH to compartments representing liver, lung, fat, kidney, GI tract, aggregated rapidly perfused tissues, and aggregated slowly perfused tissues. Metabolism by oxidation and glucuronidation was included for liver and kidneys. Rates of hepatic alpha 2u production and resorption by renal proximal tubules were taken from the literature. Degradation of liganded alpha 2u by renal lysosomal cathepsins was modeled with a K sub(m) value corresponding to the measured 30% reduction in proteolytic efficiency and with free and bound forms of alpha 2u competing for access to the enzymes. Increased pinocytotic uptake of alpha 2u into the kidney induces cathepsin activity. A model that ascribed renal alpha 2u accumulation solely to reduced lysosomal proteolysis failed to reproduce the observed accumulation. The model could reproduce experimental observations if a transient increase in hepatic synthesis of alpha 2u, stimulated by the presence of liganded alpha 2u in the blood, and accelerated secretion of the protein from the liver were assumed. This model reproduces time course data of blood and kidney TMP-2-OH and renal alpha 2u concentrations, suggesting that renal accumulation of alpha 2u is not simply a consequence of reduced proteolytic degradation but may also involve a transient increase in hepatic alpha 2u production. The model predicts increased delivery of TMP-2-OH to the kidney and consequent increased renal production of potentially toxic TMP-2-OH metabolites than would be the case if no alpha 2u were present. Induced lysosomal activity and increased production of toxic metabolites may both contribute to the nephrotoxicity observed in male rats exposed to an alpha 2u ligand or its precursor. JF - Toxicology AU - Kohn, M C AU - Melnick, R L AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop A3-06, Research Triangle Park, NC 27709, USA, kohn@valiant.niehs.nih.gov Y1 - 1999/08/31/ PY - 1999 DA - 1999 Aug 31 SP - 89 EP - 105 VL - 136 IS - 2-3 SN - 0300-483X, 0300-483X KW - rats KW - pharmacokinetics KW - 2,4,4-Trimethyl-2-pentanol KW - Toxicology Abstracts KW - Protein biosynthesis KW - Dosimetry KW - Kidney KW - Lysosomes KW - Models KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17402114?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology&rft.atitle=A+physiological+model+for+ligand-induced+accumulation+of+alpha+sub%282u%29+globulin+in+male+rat+kidney.+Roles+of+protein+synthesis+and+lysosomal+degradation+in+the+renal+dosimetry+of+2%2C4%2C4-trimethyl-2-pentanol&rft.au=Kohn%2C+M+C%3BMelnick%2C+R+L&rft.aulast=Kohn&rft.aufirst=M&rft.date=1999-08-31&rft.volume=136&rft.issue=2-3&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=Toxicology&rft.issn=0300483X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Kidney; Lysosomes; Protein biosynthesis; Dosimetry; Models ER - TY - JOUR T1 - Transmission of drug-resistant strains of HIV-1: unfortunate, but inevitable. AN - 70011580; 10475176 JF - Lancet (London, England) AU - Cohen, O J AU - Fauci, A S AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/08/28/ PY - 1999 DA - 1999 Aug 28 SP - 697 EP - 698 VL - 354 IS - 9180 SN - 0140-6736, 0140-6736 KW - Anti-HIV Agents KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Phenotype KW - Genotype KW - Humans KW - Microbial Sensitivity Tests KW - HIV-1 -- genetics KW - HIV Infections -- virology KW - Anti-HIV Agents -- therapeutic use KW - HIV Infections -- transmission KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - HIV-1 -- drug effects KW - Drug Resistance, Multiple -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70011580?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Transmission+of+drug-resistant+strains+of+HIV-1%3A+unfortunate%2C+but+inevitable.&rft.au=Cohen%2C+O+J%3BFauci%2C+A+S&rft.aulast=Cohen&rft.aufirst=O&rft.date=1999-08-28&rft.volume=354&rft.issue=9180&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-21 N1 - Date created - 1999-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Lancet. 1999 Aug 28;354(9180):729-33 [10475184] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein receptor and TG phosphorylation. AN - 69987270; 10455190 AB - Follicular thyroglobulin (TG) decreases expression of the thyroid-restricted transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, thereby suppressing expression of the sodium iodide symporter, thyroid peroxidase, TG, and thyrotropin receptor genes (Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A. , and Kohn, L. D. (1997) Proc. Natl. Acad. Sci. U. S. A. 95, 8251-8256). The ability of highly purified 27, 19, or 12 S follicular TG to suppress thyroid-restricted gene expression correlates with their ability to bind to FRTL-5 thyrocytes and is inhibited by a specific antibody to the thyroid apical membrane asialoglycoprotein receptor (ASGPR), which is related to the ASGPR of liver cells. Phosphorylating serine/threonine residues of TG, by autophosphorylation or protein kinase A, eliminates TG suppression and enhances transcript levels of the thyroid-restricted genes 2-fold in the absence of a change in TG binding to the ASGPR. Follicular TG suppression of thyroid-restricted genes is thus mediated by the ASPGR on the thyrocyte apical membrane and regulated by a signal system wherein phosphorylation of serine/threonine residues on the bound ligand is an important component. These data provide a hitherto unsuspected role for the ASGPR in transcriptional signaling, aside from its role in endocytosis. They establish a functional role for phosphorylated serine/threonine residues on the TG molecule. JF - The Journal of biological chemistry AU - Ulianich, L AU - Suzuki, K AU - Mori, A AU - Nakazato, M AU - Pietrarelli, M AU - Goldsmith, P AU - Pacifico, F AU - Consiglio, E AU - Formisano, S AU - Kohn, L D AD - Metabolic Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/08/27/ PY - 1999 DA - 1999 Aug 27 SP - 25099 EP - 25107 VL - 274 IS - 35 SN - 0021-9258, 0021-9258 KW - Asialoglycoprotein Receptor KW - 0 KW - Nuclear Proteins KW - RNA, Messenger KW - Receptors, Cell Surface KW - Recombinant Proteins KW - Transcription Factors KW - thyroid nuclear factor 1 KW - Phosphoserine KW - 17885-08-4 KW - Okadaic Acid KW - 1W21G5Q4N2 KW - Thyroglobulin KW - 9010-34-8 KW - Iodide Peroxidase KW - EC 1.11.1.8 KW - Index Medicus KW - Animals KW - Nuclear Proteins -- genetics KW - RNA, Messenger -- drug effects KW - Transcription Factors -- genetics KW - Genes, MHC Class I -- drug effects KW - Phosphoserine -- metabolism KW - Protein Binding KW - Rats KW - Phosphorylation KW - Promoter Regions, Genetic -- drug effects KW - Transfection KW - Okadaic Acid -- pharmacology KW - Suppression, Genetic KW - Iodide Peroxidase -- genetics KW - Cell Line KW - Receptors, Cell Surface -- metabolism KW - Thyroglobulin -- chemistry KW - Thyroid Gland -- drug effects KW - Gene Expression Regulation -- drug effects KW - Thyroglobulin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69987270?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Follicular+thyroglobulin+%28TG%29+suppression+of+thyroid-restricted+genes+involves+the+apical+membrane+asialoglycoprotein+receptor+and+TG+phosphorylation.&rft.au=Ulianich%2C+L%3BSuzuki%2C+K%3BMori%2C+A%3BNakazato%2C+M%3BPietrarelli%2C+M%3BGoldsmith%2C+P%3BPacifico%2C+F%3BConsiglio%2C+E%3BFormisano%2C+S%3BKohn%2C+L+D&rft.aulast=Ulianich&rft.aufirst=L&rft.date=1999-08-27&rft.volume=274&rft.issue=35&rft.spage=25099&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ATP-dependent activation of K(Ca) and ROMK-type K(ATP) channels in human submandibular gland ductal cells. AN - 69982805; 10455193 AB - [Ca(2+)](i) and membrane current were measured in human submandibular gland ductal (HSG) cells to determine the regulation of salivary cell function by ATP. 1-10 microM ATP activated internal Ca(2+) release, outward Ca(2+)-dependent K(+) channel (K(Ca)), and inward store-operated Ca(2+) current (I(SOC)). The subsequent addition of 100 microM ATP activated an inwardly rectifying K(+) current, without increasing [Ca(2+)](i). The K(+) current was also stimulated by ATP in cells treated with thapsigargin in a Ca(2+)-free medium and was blocked by glibenclamide and tolbutamide, but not by charybdotoxin. This suggests the involvement of a Ca(2+)-independent, sulfonylurea-sensitive K(+) channel (K(ATP)). UTP mimicked the low [ATP] effects, while benzoyl-ATP activated internal Ca(2+) release, a Ca(2+) influx pathway, and K(Ca). Thus, ATP acts via P(2U) (P2Y(2)) and P(2Z) (P2X(7)) receptors to increase [Ca(2+)](i) and activate K(Ca), but not K(ATP). Importantly, (i) ROMK1 and the cystic fibrosis transmembrane regulator protein (but not SUR1, SUR2A, or SUR2B) and (ii) cAMP-stimulated Cl(-) and K(+) currents were detected in HSG cells. These data demonstrate for the first time that a ROMK-type K(ATP) channel is present in salivary gland duct cells that is regulated by extracellular ATP and possibly by the cystic fibrosis transmembrane regulator. This reveals a potentially novel mechanism for K(+) secretion in these cells. JF - The Journal of biological chemistry AU - Liu, X AU - Singh, B B AU - Ambudkar, I S AD - Secretory Physiology Section, Gene Therapy and Therapeutics Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/08/27/ PY - 1999 DA - 1999 Aug 27 SP - 25121 EP - 25129 VL - 274 IS - 35 SN - 0021-9258, 0021-9258 KW - CFTR protein, human KW - 0 KW - KCNJ1 protein, human KW - Potassium Channels KW - Potassium Channels, Inwardly Rectifying KW - RNA, Messenger KW - Charybdotoxin KW - 115422-61-2 KW - Cystic Fibrosis Transmembrane Conductance Regulator KW - 126880-72-6 KW - Thapsigargin KW - 67526-95-8 KW - Lanthanum KW - 6I3K30563S KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Tolbutamide KW - 982XCM1FOI KW - Cyclic AMP KW - E0399OZS9N KW - Calcium KW - SY7Q814VUP KW - Uridine Triphosphate KW - UT0S826Z60 KW - Index Medicus KW - Thapsigargin -- pharmacology KW - Cystic Fibrosis Transmembrane Conductance Regulator -- metabolism KW - Uridine Triphosphate -- pharmacology KW - Patch-Clamp Techniques KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Lanthanum -- pharmacology KW - Humans KW - Tolbutamide -- pharmacology KW - Cyclic AMP -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Charybdotoxin -- pharmacology KW - Calcium -- metabolism KW - Potassium Channels -- metabolism KW - Submandibular Gland -- metabolism KW - Adenosine Triphosphate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69982805?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=ATP-dependent+activation+of+K%28Ca%29+and+ROMK-type+K%28ATP%29+channels+in+human+submandibular+gland+ductal+cells.&rft.au=Liu%2C+X%3BSingh%2C+B+B%3BAmbudkar%2C+I+S&rft.aulast=Liu&rft.aufirst=X&rft.date=1999-08-27&rft.volume=274&rft.issue=35&rft.spage=25121&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuronal sensitivity to tetanus toxin requires gangliosides. AN - 69981705; 10455200 AB - Tetanus toxin produces spastic paralysis in situ by blocking inhibitory neurotransmitter release in the spinal cord. Although di- and trisialogangliosides bind tetanus toxin, their role as productive toxin receptors remains unclear. We examined toxin binding and action in spinal cord cell cultures grown in the presence of fumonisin B(1), an inhibitor of ganglioside synthesis. Mouse spinal cord neurons grown for 3 weeks in culture in 20 microM fumonisin B(1) develop dendrites, axons, and synaptic terminals similar to untreated neurons, even though thin layer chromatography shows a greater than 90% inhibition of ganglioside synthesis. Absence of tetanus and cholera toxin binding by toxin-horseradish peroxidase conjugates or immunofluorescence further indicates loss of mono- and polysialogangliosides. In contrast to control cultures, tetanus toxin added to fumonisin B(1)-treated cultures does not block potassium-stimulated glycine release, inhibit activity-dependent uptake of FM1-43, or abolish immunoreactivity for vesicle-associated membrane protein, the toxin substrate. Supplementing fumonisin B(1)-treated cultures with mixed brain gangliosides completely restores the ability of tetanus toxin to bind to the neuronal surface and to block neurotransmitter release. These data demonstrate that fumonisin B(1) protects against toxin-induced synaptic blockade and that gangliosides are a necessary component of the receptor mechanism for tetanus toxin. JF - The Journal of biological chemistry AU - Williamson, L C AU - Bateman, K E AU - Clifford, J C AU - Neale, E A AD - Laboratory of Developmental Neurobiology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892-4480, USA. Y1 - 1999/08/27/ PY - 1999 DA - 1999 Aug 27 SP - 25173 EP - 25180 VL - 274 IS - 35 SN - 0021-9258, 0021-9258 KW - Carboxylic Acids KW - 0 KW - Enzyme Inhibitors KW - FM1 43 KW - Fumonisins KW - Gangliosides KW - Membrane Proteins KW - Peptide Fragments KW - Pyridinium Compounds KW - Quaternary Ammonium Compounds KW - R-SNARE Proteins KW - Tetanus Toxin KW - fumonisin B1 KW - 3ZZM97XZ32 KW - Oxidoreductases KW - EC 1.- KW - dihydroceramide desaturase KW - EC 1.3.1.- KW - Glycine KW - TE7660XO1C KW - Index Medicus KW - Quaternary Ammonium Compounds -- metabolism KW - Animals KW - Microscopy, Phase-Contrast KW - Glycine -- metabolism KW - Membrane Proteins -- metabolism KW - Mice KW - Oxidoreductases -- antagonists & inhibitors KW - Protein Binding KW - Cell Size -- drug effects KW - Pyridinium Compounds -- metabolism KW - Cells, Cultured KW - Enzyme Inhibitors -- pharmacology KW - Fluorescent Antibody Technique KW - Gangliosides -- pharmacology KW - Neurons -- drug effects KW - Spinal Cord -- drug effects KW - Carboxylic Acids -- pharmacology KW - Tetanus Toxin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69981705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Neuronal+sensitivity+to+tetanus+toxin+requires+gangliosides.&rft.au=Williamson%2C+L+C%3BBateman%2C+K+E%3BClifford%2C+J+C%3BNeale%2C+E+A&rft.aulast=Williamson&rft.aufirst=L&rft.date=1999-08-27&rft.volume=274&rft.issue=35&rft.spage=25173&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Replication protein A stimulates proliferating cell nuclear antigen-dependent repair of abasic sites in DNA by human cell extracts. AN - 69985410; 10460157 AB - Base excision repair (BER) pathway is the major cellular process for removal of endogenous base lesions and apurinic/apyrimidinic (AP) sites in DNA. There are two base excision repair subpathways in mammalian cells, characterized by the number of nucleotides synthesized into the excision patch. They are the "single-nucleotide" (one nucleotide incorporated) and the "long-patch" (several nucleotides incorporated) BER pathways. Proliferating cell nuclear antigen (PCNA) is known to be an essential factor in long-patch base excision repair. We have studied the role of replication protein A (RPA) in PCNA-dependent, long-patch BER of AP sites in human cell extracts. PCNA and RPA were separated from the other BER proteins by fractionation of human whole-cell extract on a phosphocellulose column. The protein fraction PC-FII (phosphocellulose fraction II), which does not contain RPA and PCNA but otherwise contains all core BER proteins required for PCNA-dependent BER (AP endonuclease, DNA polymerases delta, beta and DNA ligase, and FEN1 endonuclease), had reduced ability to repair plasmid DNA containing AP sites. Purified PCNA or RPA, when added separately, could only partially restore the PC-FII repair activity of AP sites. However, additions of both proteins together greatly stimulated AP site repair by PC-FII. These results demonstrate a role for RPA in PCNA-dependent BER of AP sites. JF - Biochemistry AU - Dianov, G L AU - Jensen, B R AU - Kenny, M K AU - Bohr, V A AD - Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. dianovg@grc.nia.nih.gov Y1 - 1999/08/24/ PY - 1999 DA - 1999 Aug 24 SP - 11021 EP - 11025 VL - 38 IS - 34 SN - 0006-2960, 0006-2960 KW - Cation Exchange Resins KW - 0 KW - DNA-Binding Proteins KW - Proliferating Cell Nuclear Antigen KW - RPA1 protein, human KW - Replication Protein A KW - Cellulose KW - 9004-34-6 KW - DNA KW - 9007-49-2 KW - phosphocellulose KW - 9015-14-9 KW - Deoxyribonuclease IV (Phage T4-Induced) KW - EC 3.1.21.2 KW - Carbon-Oxygen Lyases KW - EC 4.2.- KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - EC 4.2.99.18 KW - Index Medicus KW - Cell Fractionation KW - Cellulose -- analogs & derivatives KW - Base Sequence KW - Chromatography, Gel KW - Humans KW - Molecular Sequence Data KW - Drug Synergism KW - Carbon-Oxygen Lyases -- metabolism KW - DNA Repair KW - Proliferating Cell Nuclear Antigen -- physiology KW - DNA -- metabolism KW - Lymphocytes -- enzymology KW - Lymphocytes -- metabolism KW - DNA-Binding Proteins -- physiology KW - Proliferating Cell Nuclear Antigen -- isolation & purification KW - DNA-Binding Proteins -- isolation & purification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69985410?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Replication+protein+A+stimulates+proliferating+cell+nuclear+antigen-dependent+repair+of+abasic+sites+in+DNA+by+human+cell+extracts.&rft.au=Dianov%2C+G+L%3BJensen%2C+B+R%3BKenny%2C+M+K%3BBohr%2C+V+A&rft.aulast=Dianov&rft.aufirst=G&rft.date=1999-08-24&rft.volume=38&rft.issue=34&rft.spage=11021&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. AN - 69981144; 10458725 AB - Coadministration of phentermine and fenfluramine (phen/fen) effectively treats obesity and possibly addictive disorders. The association of fenfluramine and certain other anorexic agents with serious side effects, such as cardiac valvulopathy and primary pulmonary hypertension (PPH), limits the clinical utility of these drugs. Development of new medications that produce neurochemical effects like phen/fen without causing unwanted side effects would be a significant therapeutic breakthrough. We tested the hypothesis that fenfluramine (and other anorexic agents) might increase the risk of PPH through interactions with serotonin (5-HT) transporters. Because 5-HT transporter proteins in the lung and brain are identical, we examined, in rat brain, the effects of selected drugs on 5-HT efflux in vivo and monoamine transporters in vitro as a generalized index of transporter function. Our data show that drugs known or suspected to increase the risk of PPH (eg, aminorex, fenfluramine, and chlorphentermine) are 5-HT transporter substrates, whereas drugs that have not been shown to increase the risk of PPH are less potent in this regard. We speculate that medications that are 5-HT transporter substrates get translocated into pulmonary cells where, depending on the degree of drug retention, their intrinsic drug toxicity, and individual susceptibility, PPH could develop as a response to high levels of these drugs or metabolites. Emerging evidence suggests that it is possible to develop transporter substrates devoid of adverse side effects. Such medications could have therapeutic application in the management of obesity, drug dependence, depression, and other disorders. JF - Circulation AU - Rothman, R B AU - Ayestas, M A AU - Dersch, C M AU - Baumann, M H AD - Clinical Psychopharmacology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Md, USA. rrothman@intra.nida.nih.gov Y1 - 1999/08/24/ PY - 1999 DA - 1999 Aug 24 SP - 869 EP - 875 VL - 100 IS - 8 KW - Appetite Depressants KW - 0 KW - Carrier Proteins KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Serotonin Plasma Membrane Transport Proteins KW - Slc6a4 protein, rat KW - Fenfluramine KW - 2DS058H2CF KW - Aminorex KW - 2SH16612I9 KW - Serotonin KW - 333DO1RDJY KW - Chlorphentermine KW - NHW07912O7 KW - Dopamine KW - VTD58H1Z2X KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Microdialysis KW - Animals KW - Rats, Sprague-Dawley KW - Dopamine -- metabolism KW - Brain -- metabolism KW - Male KW - Aminorex -- metabolism KW - Hypertension, Pulmonary -- chemically induced KW - Fenfluramine -- metabolism KW - Carrier Proteins -- metabolism KW - Serotonin -- metabolism KW - Appetite Depressants -- metabolism KW - Chlorphentermine -- metabolism KW - Membrane Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69981144?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Aminorex%2C+fenfluramine%2C+and+chlorphentermine+are+serotonin+transporter+substrates.+Implications+for+primary+pulmonary+hypertension.&rft.au=Rothman%2C+R+B%3BAyestas%2C+M+A%3BDersch%2C+C+M%3BBaumann%2C+M+H&rft.aulast=Rothman&rft.aufirst=R&rft.date=1999-08-24&rft.volume=100&rft.issue=8&rft.spage=869&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-13 N1 - Date created - 1999-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene. AN - 69971475; 10446164 AB - Microsomal epoxide hydrolase (mEH) is a conserved enzyme that is known to hydrolyze many drugs and carcinogens, and a few endogenous steroids and bile acids. mEH-null mice were produced and found to be fertile and have no phenotypic abnormalities thus indicating that mEH is not critical for reproduction and physiological homeostasis. mEH has also been implicated in participating in the metabolic activation of polycyclic aromatic hydrocarbon carcinogens. Embryonic fibroblast derived from the mEH-null mice were unable to produce the proximate carcinogenic metabolite of 7,12-dimethylbenz[a]anthracene (DMBA), a widely studied experimental prototype for the polycylic aromatic hydrocarbon class of chemical carcinogens. They were also resistant to DMBA-mediated toxicity. Using the two-stage initiation-promotion skin cancer bioassay, the mEH-null mice were found to be highly resistant to DMBA-induced carcinogenesis. In a complete carcinogenesis bioassay, the mEH mice were totally resistant to tumorigenesis. These data establish in an intact animal model that mEH is a key genetic determinant in DMBA carcinogenesis through its role in production of the ultimate carcinogenic metabolite of DMBA, the 3,4-diol-1,2-epoxide. JF - The Journal of biological chemistry AU - Miyata, M AU - Kudo, G AU - Lee, Y H AU - Yang, T J AU - Gelboin, H V AU - Fernandez-Salguero, P AU - Kimura, S AU - Gonzalez, F J AD - Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/08/20/ PY - 1999 DA - 1999 Aug 20 SP - 23963 EP - 23968 VL - 274 IS - 34 SN - 0021-9258, 0021-9258 KW - Carcinogens KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - Cyp1b1 protein, mouse KW - Cytochrome P-450 CYP1B1 KW - Epoxide Hydrolases KW - EC 3.3.2.- KW - Index Medicus KW - Animals KW - Skin Neoplasms -- chemically induced KW - Cytochrome P-450 Enzyme System -- physiology KW - Mice, Inbred C57BL KW - Mice KW - Female KW - Mice, Knockout KW - Epoxide Hydrolases -- genetics KW - Epoxide Hydrolases -- physiology KW - 9,10-Dimethyl-1,2-benzanthracene -- toxicity KW - Microsomes, Liver -- enzymology KW - Carcinogens -- toxicity KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69971475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Targeted+disruption+of+the+microsomal+epoxide+hydrolase+gene.+Microsomal+epoxide+hydrolase+is+required+for+the+carcinogenic+activity+of+7%2C12-dimethylbenz%5Ba%5Danthracene.&rft.au=Miyata%2C+M%3BKudo%2C+G%3BLee%2C+Y+H%3BYang%2C+T+J%3BGelboin%2C+H+V%3BFernandez-Salguero%2C+P%3BKimura%2C+S%3BGonzalez%2C+F+J&rft.aulast=Miyata&rft.aufirst=M&rft.date=1999-08-20&rft.volume=274&rft.issue=34&rft.spage=23963&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis. AN - 70016743; 10467420 AB - beta-catenin activation, and subsequent upregulation of Wnt-signaling, is an important event in the development of certain human and rodent cancers. Recently, mutations in the beta-catenin gene in the region of the serine-threonine glycogen kinase (GSK)-3beta phosphorylation target sites have been identified in hepatocellular neoplasms from humans and transgenic mice. In this study we examined 152 hepatocellular neoplasms from B6C3F1 mice included in five chemical treatment groups and controls for mutations in the beta-catenin gene. Twenty of 29 hepatocellular neoplasms from mice treated with methyleugenol had point mutations at codons 32, 33, 34 or 41, sites which are mutated in colon and other cancers. Likewise, nine of 24 methylene chloride-induced hepatocellular neoplasms and 18 of 42 oxazepam-induced neoplasms exhibited similar mutations. In contrast, only three of 18 vinyl carbamate-induced liver tumors, one of 18 TCDD-induced liver tumors, and two of 22 spontaneous liver neoplasms had mutations in beta-catenin. Thus, there appears to be a chemical specific involvement of beta-catenin activation in mouse hepatocellular carcinogenesis. Expression analyses using Western blot and immunohistochemistry indicate that beta-catenin protein accumulates along cell membranes following mutation. The finding of mutations in both adenomas and carcinomas from diverse chemical treatment groups and the immunostaining of beta-catenin protein in an altered hepatocellular focus suggest that these alterations are early events in mouse hepatocellular carcinogenesis. JF - Oncogene AU - Devereux, T R AU - Anna, C H AU - Foley, J F AU - White, C M AU - Sills, R C AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, NIEHS, Research Triangle Park, North Carolina, NC 27709, USA. Y1 - 1999/08/19/ PY - 1999 DA - 1999 Aug 19 SP - 4726 EP - 4733 VL - 18 IS - 33 SN - 0950-9232, 0950-9232 KW - CTNNB1 protein, mouse KW - 0 KW - Carcinogens KW - Cytoskeletal Proteins KW - Mutagens KW - Trans-Activators KW - beta Catenin KW - Index Medicus KW - Polymerase Chain Reaction KW - Carcinogens -- pharmacology KW - Animals KW - Exons KW - Dose-Response Relationship, Drug KW - Mice KW - Sequence Analysis, DNA KW - Mutagens -- pharmacology KW - Polymorphism, Single-Stranded Conformational KW - Liver Neoplasms -- pathology KW - Adenoma, Liver Cell -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Liver Neoplasms -- chemically induced KW - Carcinoma, Hepatocellular -- pathology KW - Adenoma, Liver Cell -- pathology KW - Adenoma, Liver Cell -- chemically induced KW - Carcinoma, Hepatocellular -- chemically induced KW - Liver Neoplasms -- genetics KW - Cytoskeletal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70016743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Mutation+of+beta-catenin+is+an+early+event+in+chemically+induced+mouse+hepatocellular+carcinogenesis.&rft.au=Devereux%2C+T+R%3BAnna%2C+C+H%3BFoley%2C+J+F%3BWhite%2C+C+M%3BSills%2C+R+C%3BBarrett%2C+J+C&rft.aulast=Devereux&rft.aufirst=T&rft.date=1999-08-19&rft.volume=18&rft.issue=33&rft.spage=4726&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-15 N1 - Date created - 1999-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug-induced apoptosis is delayed and reduced in XPD lymphoblastoid cell lines: possible role of TFIIH in p53-mediated apoptotic cell death. AN - 70011689; 10467415 AB - The tumor suppressor gene product p53 can bind to and inhibit the helicase activity of the multisubunit transcription-repair factor TFIIH. We previously reported that p53-mediated apoptosis is attenuated in primary human fibroblasts from individuals with Xeroderma Pigmentosum (XP) that harbor mutations in the TFIIH DNA helicases XPD or XPB. In this study we show that apoptosis is reduced and delayed in three XPD lymphoblastoid cell lines (LCLs), but not in an XPD heterozygote LCL, after exposure to doxorubicin, a DNA-damaging agent and topoisomerase II inhibitor frequently used in cancer therapy. Apoptosis was assessed by quantitation of Annexin V binding to exposed phosphatidylserine residues and by caspase-mediated cleavage of Poly(ADP)Ribose Polymerase (PARP). Apoptosis induced by doxorubicin was suppressed in LCLs retrovirally transduced with the Human Papillomavirus 16 E6 oncoprotein, consistent with the hypothesis that this is a p53-dependent process. PARP cleavage was not delayed in XPD LCLs in response to anti-Fas (CD95) antibody-mediated apoptosis, thus, the defect in the apoptotic pathway in these cells lies upstream of caspase activation. Similar changes in the expression of apoptosis-effector genes, p53, and p53-responsive genes p21Cip1/WAF-1/Sid1 (p21), gadd45, bcl-2 and bax were observed in normal and XPD LCLs after treatment with doxorubicin, indicating that delayed apoptosis was not a consequence of defective transcription of these genes. Thus, our studies provide further support to the hypothesis that XPD and p53 can functionally interact in a p53-mediated apoptotic pathway. JF - Oncogene AU - Robles, A I AU - Wang, X W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892-4255, USA. Y1 - 1999/08/19/ PY - 1999 DA - 1999 Aug 19 SP - 4681 EP - 4688 VL - 18 IS - 33 SN - 0950-9232, 0950-9232 KW - Antineoplastic Agents KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Topoisomerase II Inhibitors KW - Transcription Factors KW - Transcription Factors, TFII KW - Tumor Suppressor Protein p53 KW - Transcription Factor TFIIH KW - 148710-81-0 KW - Doxorubicin KW - 80168379AG KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Hematopoietic Stem Cells KW - Dose-Response Relationship, Drug KW - Humans KW - Heterozygote KW - Lymphocytes KW - Antineoplastic Agents -- pharmacology KW - Cell Line KW - Apoptosis KW - Doxorubicin -- pharmacology KW - DNA Helicases -- genetics KW - Xeroderma Pigmentosum -- genetics KW - Tumor Suppressor Protein p53 -- metabolism KW - Transcription Factors -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70011689?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Drug-induced+apoptosis+is+delayed+and+reduced+in+XPD+lymphoblastoid+cell+lines%3A+possible+role+of+TFIIH+in+p53-mediated+apoptotic+cell+death.&rft.au=Robles%2C+A+I%3BWang%2C+X+W%3BHarris%2C+C+C&rft.aulast=Robles&rft.aufirst=A&rft.date=1999-08-19&rft.volume=18&rft.issue=33&rft.spage=4681&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-15 N1 - Date created - 1999-10-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cigarette smoking AN - 17327169; 4593878 AB - Cigarette smoking is the largest preventable risk factor for morbidity and mortality in developed countries. Dramatic changes in the prevalence of cigarette smoking in the second half of this century in the United States (i.e., a reduction among men and an increase among women) have reduced current smoking levels to approximately one quarter of the adult population and have reduced differences in smoking prevalence and smoking-attributable diseases between the sexes. Current smoking in the United States is positively associated with younger age, lower income, reduced educational achievement, and disadvantaged neighborhood environment. Daily smokers smoke cigarettes to maintain nicotine levels in the brain, primarily to avoid the negative effects of nicotine withdrawal, but also to modulate mood. Regular smokers exhibit higher and lower levels of stress and arousal, respectively, than nonsmokers, as well as higher impulsivity and neuroticism trait values. Nicotine dependence is the single most common psychiatric diagnosis in the United States, and substance abuse, major depression, and anxiety disorders are the most prevalent psychiatric comorbid conditions associated with nicotine dependence. Studies in twins have implicated genetic factors that explain most of the variability in vulnerability to smoking and in persistence of the smoking phenotype. Future research into the causes of smoking must take into account these associated demographics, social factors, comorbid psychiatric conditions, and genetic factors to understand this complex human behavior. JF - Journal of the National Cancer Institute AU - Bergen, A W AU - Caporaso, N AD - National Institutes of Health, Executive Plaza South, Rm. 7110, Bethesda, MD 20892, USA, Bergena@epndce.nci.nih.gov Y1 - 1999/08/18/ PY - 1999 DA - 1999 Aug 18 SP - 1365 EP - 1375 VL - 91 IS - 16 SN - 0027-8874, 0027-8874 KW - Risk Abstracts; Health & Safety Science Abstracts KW - Mortality KW - Age KW - Socioeconomics KW - Morbidity KW - Cigarette smoking KW - R2 23060:Medical and environmental health KW - H 4000:Food and Drugs UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17327169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Cigarette+smoking&rft.au=Bergen%2C+A+W%3BCaporaso%2C+N&rft.aulast=Bergen&rft.aufirst=A&rft.date=1999-08-18&rft.volume=91&rft.issue=16&rft.spage=1365&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Morbidity; Socioeconomics; Mortality; Cigarette smoking; Age ER - TY - JOUR T1 - Receptor-mediated uptake of an extracellular Bcl-x(L) fusion protein inhibits apoptosis. AN - 69977405; 10449732 AB - Bcl-x(L), a member of the Bcl-2 family, inhibits many pathways of apoptosis when overexpressed in the cell cytosol. We examined the capacity of Bcl-x(L) fusion proteins to bind cells from the outside and block apoptosis. Full-length Bcl-x(L) protein at micromolar concentrations did not affect apoptosis when added to cell media. To increase uptake by cells, Bcl-x(L) was fused to the receptor-binding domain of diphtheria toxin (DTR). The Bcl-x(L)-DTR fusion protein blocked apoptosis induced by staurosporine, gamma-irradiation, and poliovirus in a variety of cell types when added to media. The potency of inhibition of poliovirus-induced apoptosis by Bcl-x(L)-DTR was greater than that of strong caspase inhibitors. Brefeldin A, an inhibitor of vesicular traffic between the endoplasmic reticulum and Golgi apparatus, prevented the Bcl-x(L)-DTR blockade of apoptosis induced by staurosporine, suggesting that Bcl-x(L)-DTR must be endocytosed and reach intracellular compartments for activity. Many diseases are caused by overexpression or underexpression of Bcl-x(L) homologues. Extracellular delivery of Bcl-2 family member proteins may have a wide range of uses in promoting or preventing cell death. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Liu, X H AU - Castelli, J C AU - Youle, R J AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/08/17/ PY - 1999 DA - 1999 Aug 17 SP - 9563 EP - 9567 VL - 96 IS - 17 SN - 0027-8424, 0027-8424 KW - BCL2L1 protein, human KW - 0 KW - Diphtheria Toxin KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Fusion Proteins KW - bcl-X Protein KW - Brefeldin A KW - 20350-15-6 KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - Staurosporine KW - H88EPA0A3N KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Endoplasmic Reticulum -- metabolism KW - Endocytosis KW - Staurosporine -- pharmacology KW - HeLa Cells KW - Humans KW - Golgi Apparatus -- drug effects KW - Recombinant Fusion Proteins -- pharmacology KW - Brefeldin A -- pharmacology KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Golgi Apparatus -- metabolism KW - Protein Conformation KW - Endoplasmic Reticulum -- drug effects KW - Apoptosis -- drug effects KW - Diphtheria Toxin -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- pharmacology KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Diphtheria Toxin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69977405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Receptor-mediated+uptake+of+an+extracellular+Bcl-x%28L%29+fusion+protein+inhibits+apoptosis.&rft.au=Liu%2C+X+H%3BCastelli%2C+J+C%3BYoule%2C+R+J&rft.aulast=Liu&rft.aufirst=X&rft.date=1999-08-17&rft.volume=96&rft.issue=17&rft.spage=9563&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1981 Jan;78(1):172-6 [6264431] Proc Natl Acad Sci U S A. 1999 May 11;96(10):5492-7 [10318911] Harvey Lect. 1980-1981;76:45-73 [6813290] Proc Natl Acad Sci U S A. 1983 Nov;80(22):6853-7 [6316330] Science. 1987 Oct 23;238(4826):536-9 [3498987] J Cell Biol. 1991 Jun;113(5):1025-32 [2040642] Cell. 1991 Nov 1;67(3):601-16 [1682055] Cell. 1991 Nov 1;67(3):617-27 [1934063] Biochemistry. 1992 Apr 14;31(14):3555-9 [1567815] Cancer Res. 1993 Oct 1;53(19):4701-14 [8402648] Cell. 1994 Mar 25;76(6):1039-51 [7511061] Neuron. 1994 Oct;13(4):1017-30 [7946326] J Immunol. 1995 Mar 1;154(5):2023-32 [7532659] Biochemistry. 1995 Apr 11;34(14):4856-63 [7718592] J Immunol. 1995 Nov 15;155(10):4644-52 [7594463] Immunity. 1996 Mar;4(3):195-201 [8624810] J Biol Chem. 1996 Mar 1;271(9):4573-6 [8617712] Nature. 1996 May 23;381(6580):335-41 [8692274] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8437-42 [8710889] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14559-63 [8962091] Nature. 1978 Feb 23;271(5647):752-5 [625344] Nature. 1997 Jan 23;385(6614):353-7 [9002522] Nature. 1997 Jan 30;385(6615):434-9 [9009190] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3668-72 [9108035] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3759-64 [9108051] Proc Natl Acad Sci U S A. 1997 May 13;94(10):5113-8 [9144199] Adv Pharmacol. 1997;41:295-336 [9204150] Science. 1997 Jul 18;277(5324):370-2 [9219694] J Exp Med. 1997 Sep 15;186(6):967-72 [9294150] J Cell Biol. 1997 Oct 6;139(1):205-17 [9314540] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11357-62 [9326614] J Cell Biol. 1997 Dec 1;139(5):1281-92 [9382873] Nat Med. 1997 Dec;3(12):1362-8 [9396606] Infect Immun. 1998 Feb;66(2):615-9 [9453617] EMBO J. 1998 Jul 15;17(14):3878-85 [9670005] Proc Natl Acad Sci U S A. 1981 Aug;78(8):4950-4 [6272284] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion AN - 17327764; 4596833 AB - Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes. Until now, the question of whether AP-1 transactivation is required for carcinogenesis in vivo has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant c-jun (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14-TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ. TAM67 expression blocked 12-O-tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13- acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3. More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention. JF - Proceedings of the National Academy of Sciences, USA AU - Young, M R AU - Li, J AU - Rincon, M AU - Flavell, R A AU - Sathyanarayana, B K AU - Hunziker, R AU - Colburn, N AD - Basic Research Laboratory-Basic Research Program, National Cancer Institute, Frederick, MD 21702 USA, youngm@ncifcrf.gov Y1 - 1999/08/17/ PY - 1999 DA - 1999 Aug 17 SP - 9827 EP - 9832 VL - 96 IS - 17 SN - 0027-8424, 0027-8424 KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Oncogenes & Growth Factors Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Interstitial collagenase KW - Phorbol esters KW - Stromelysin 3 KW - Carcinogenesis KW - W3 33056:Animal models of human disease KW - B 26230:Jun/Jun-B/Jun-D/AP-1 protein KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17327764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Transgenic+mice+demonstrate+AP-1+%28activator+protein-1%29+transactivation+is+required+for+tumor+promotion&rft.au=Young%2C+M+R%3BLi%2C+J%3BRincon%2C+M%3BFlavell%2C+R+A%3BSathyanarayana%2C+B+K%3BHunziker%2C+R%3BColburn%2C+N&rft.aulast=Young&rft.aufirst=M&rft.date=1999-08-17&rft.volume=96&rft.issue=17&rft.spage=9827&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.17.9827 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Stromelysin 3; Phorbol esters; Interstitial collagenase DO - http://dx.doi.org/10.1073/pnas.96.17.9827 ER - TY - JOUR T1 - Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis. AN - 69976825; 10449524 AB - Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction. To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI. In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues. Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction. Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappaB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases. JF - The Journal of experimental medicine AU - Song, X y AU - Zeng, L AU - Jin, W AU - Thompson, J AU - Mizel, D E AU - Lei, K AU - Billinghurst, R C AU - Poole, A R AU - Wahl, S M AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-4352, USA. Y1 - 1999/08/16/ PY - 1999 DA - 1999 Aug 16 SP - 535 EP - 542 VL - 190 IS - 4 SN - 0022-1007, 0022-1007 KW - Inflammation Mediators KW - 0 KW - Proteinase Inhibitory Proteins, Secretory KW - Proteins KW - Recombinant Proteins KW - SLPI protein, human KW - Secretory Leukocyte Peptidase Inhibitor KW - Serine Proteinase Inhibitors KW - Slpi protein, rat KW - Index Medicus KW - Animals KW - Rats, Inbred Lew KW - Cell Wall KW - Amino Acid Sequence KW - Sequence Analysis, DNA KW - Streptococcus pyogenes KW - Cloning, Molecular KW - Inflammation Mediators -- metabolism KW - Extremities -- pathology KW - Rats KW - Base Sequence KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Recombinant Proteins -- therapeutic use KW - Female KW - Joints -- pathology KW - Proteins -- therapeutic use KW - Serine Proteinase Inhibitors -- therapeutic use KW - Arthritis -- chemically induced KW - Serine Proteinase Inhibitors -- genetics KW - Joints -- drug effects KW - Arthritis -- drug therapy KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69976825?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Secretory+leukocyte+protease+inhibitor+suppresses+the+inflammation+and+joint+damage+of+bacterial+cell+wall-induced+arthritis.&rft.au=Song%2C+X+y%3BZeng%2C+L%3BJin%2C+W%3BThompson%2C+J%3BMizel%2C+D+E%3BLei%2C+K%3BBillinghurst%2C+R+C%3BPoole%2C+A+R%3BWahl%2C+S+M&rft.aulast=Song&rft.aufirst=X&rft.date=1999-08-16&rft.volume=190&rft.issue=4&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-10 N1 - Date created - 1999-09-10 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF178426; GENBANK N1 - SuppNotes - Cited By: J Clin Invest. 1982 Feb;69(2):384-93 [6915940] Arthritis Rheum. 1999 Jun;42(6):1119-27 [10366104] Proc Natl Acad Sci U S A. 1986 Sep;83(18):6692-6 [3462719] J Clin Invest. 1987 Mar;79(3):669-74 [3546374] Eur J Respir Dis Suppl. 1987;153:78-85 [2448162] Biochemistry. 1988 Apr 19;27(8):2641-6 [3042021] Biol Chem Hoppe Seyler. 1988 May;369 Suppl:79-82 [3060147] N Engl J Med. 1989 Feb 9;320(6):365-76 [2536474] J Histochem Cytochem. 1989 Apr;37(4):493-8 [2926127] J Immunol. 1989 Nov 1;143(9):2961-8 [2681419] J Biol Chem. 1990 May 15;265(14):7976-81 [2110563] Biochem J. 1991 Feb 15;274 ( Pt 1):269-73 [2001242] Semin Arthritis Rheum. 1991 Jun;20(6 Suppl 2):2-11 [1866627] Arch Biochem Biophys. 1992 Apr;294(1):144-6 [1497704] Calcif Tissue Int. 1992 Apr;50(4):327-35 [1571844] Biol Chem Hoppe Seyler. 1992 Mar;373(3):111-8 [1586451] Eur J Biochem. 1992 Jul 15;207(2):773-9 [1633826] Matrix Suppl. 1992;1:37-44 [1480063] Agents Actions. 1978 Jan;8(1-2):11-8 [345779] J Biochem. 1979 Jan;85(1):157-62 [762040] Anal Biochem. 1979 Nov 1;99(2):316-20 [574722] J Biol Chem. 1980 Sep 25;255(18):8848-58 [6902725] Ann Rheum Dis. 1993 Jan;52(1):27-31 [8427510] Eur J Biochem. 1993 Dec 15;218(3):951-7 [7904240] Am J Respir Cell Mol Biol. 1994 Dec;11(6):733-41 [7946401] J Clin Invest. 1995 Jul;96(1):456-64 [7615818] Infect Immun. 1996 Nov;64(11):4520-4 [8890201] Cell. 1997 Feb 7;88(3):417-26 [9039268] J Clin Invest. 1997 Mar 1;99(5):894-900 [9062347] J Clin Invest. 1997 Apr 1;99(7):1534-45 [9119997] Biochem Biophys Res Commun. 1997 Mar 27;232(3):687-97 [9126337] Blood. 1997 Aug 1;90(3):1141-9 [9242546] Biol Chem. 1997 Sep;378(9):1055-8 [9348116] Inflamm Res. 1997 Dec;46(12):503-8 [9459081] Biochem J. 1998 Mar 1;330 ( Pt 2):897-902 [9480907] Annu Rev Immunol. 1998;16:225-60 [9597130] Infect Immun. 1998 Jun;66(6):2447-52 [9596701] J Clin Invest. 1998 Jun 15;101(12):2615-21 [9637694] J Immunol. 1998 Dec 1;161(11):6297-304 [9834119] Am J Pathol. 1999 Jan;154(1):239-47 [9916938] Scand J Clin Lab Invest. 1983 Sep;43(5):427-32 [6557666] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics and antitumor activity of a bivalent disulfide-stabilized Fv immunotoxin with improved antigen binding to erbB2. AN - 69992661; 10463601 AB - We have generated a stable bivalent Fv molecule [(dsFv)2] of the anti-erbB2 monoclonal antibody e23 in which the V(H) and V(L) domains of the Fv are linked to each other by a disulfide bond and the two Fvs are connected by a 15-amino acid linker (T. K. Bera et al., J. Mol. Biol., 281: 475-483, 1998). The e23 (dsFv)2 molecule is linked to a truncated form of Pseudomonas exotoxin (PE38) to generate a bivalent disulfide-stabilized immunotoxin e23 (dsFv)2-PE38. Compared to the monovalent immunotoxin, the (dsFv)2 immunotoxin showed greatly increased cytotoxicity to four cancer cell lines expressing low levels of erbB2 but not to four other cell lines with high erbB2 expression. e23 (dsFv)2-PE38 was administered i.v. to mice, and its half-life was determined. The t(1/2)alpha and t(1/2)beta were 20 and 325 min, respectively, whereas the corresponding values for the monovalent dsFv immunotoxin were shorter, 6 and 52 min. The antitumor activities of the monovalent and bivalent immunotoxin were compared using mice bearing A431 tumors. Despite the fact that e23 (dsFv)2-PE38 was 13-fold more active than e23 dsFv-PE38 on A431 cells in cell culture, its antitumor activity in mice was <2-fold that of the monovalent immunotoxin. These data show that a large increase in avidity does not always lead to an increase in cytotoxic activity. Furthermore, in one of the cases in which cytotoxic activity in vitro was greatly enhanced, there was only a small increase in antitumor activity. JF - Cancer research AU - Bera, T K AU - Viner, J AU - Brinkmann, E AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/08/15/ PY - 1999 DA - 1999 Aug 15 SP - 4018 EP - 4022 VL - 59 IS - 16 SN - 0008-5472, 0008-5472 KW - Antibodies, Monoclonal KW - 0 KW - Exotoxins KW - Immunoglobulin Fab Fragments KW - Immunotoxins KW - Sulfides KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Mice KW - Mice, Inbred BALB C KW - Female KW - Antibodies, Monoclonal -- immunology KW - Immunotoxins -- pharmacokinetics KW - Exotoxins -- administration & dosage KW - Neoplasms, Experimental -- immunology KW - Immunoglobulin Fab Fragments -- administration & dosage KW - Receptor, ErbB-2 -- immunology KW - Immunoglobulin Fab Fragments -- immunology KW - Neoplasms, Experimental -- drug therapy KW - Immunotoxins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69992661?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Pharmacokinetics+and+antitumor+activity+of+a+bivalent+disulfide-stabilized+Fv+immunotoxin+with+improved+antigen+binding+to+erbB2.&rft.au=Bera%2C+T+K%3BViner%2C+J%3BBrinkmann%2C+E%3BPastan%2C+I&rft.aulast=Bera&rft.aufirst=T&rft.date=1999-08-15&rft.volume=59&rft.issue=16&rft.spage=4018&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-16 N1 - Date created - 1999-09-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta. AN - 69984613; 10458907 AB - The Saccharomyces cerevisiae RAD30 gene encodes a novel eukaryotic DNA polymerase, pol eta that is able to replicate across cis-syn cyclobutane pyrimidine dimers both accurately and efficiently. Very recently, a human homolog of RAD30 was identified, mutations in which result in the sunlight-sensitive, cancer-prone, Xeroderma pigmentosum variant group phenotype. We report here the cloning and localization of a second human homolog of RAD30. Interestingly, RAD30B is localized on chromosome 18q21.1 in a region that is often implicated in the etiology of many human cancers. The mouse homolog (Rad30b) is located on chromosome 18E2. The human RAD30B and mouse Rad30b mRNA transcripts, like many repair proteins, are highly expressed in the testis. In situ hybridization analysis indicates that expression of mouse Rad30b occurs predominantly in postmeiotic round spermatids. Database searches revealed genomic and EST sequences from other eukaryotes such as Aspergillus nidulans, Schizosaccharomyces pombe, Brugia malayi, Caenorhabditis elegans, Trypanosoma cruzi, Arabidopsis thaliana, and Drosophila melanogaster that also encode putative homologs of RAD30, thereby suggesting that Rad30-dependent translesion DNA synthesis is conserved within the eukaryotic kingdom. Copyright 1999 Academic Press. JF - Genomics AU - McDonald, J P AU - Rapić-Otrin, V AU - Epstein, J A AU - Broughton, B C AU - Wang, X AU - Lehmann, A R AU - Wolgemuth, D J AU - Woodgate, R AD - Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, Maryland, 20892-2725, USA. Y1 - 1999/08/15/ PY - 1999 DA - 1999 Aug 15 SP - 20 EP - 30 VL - 60 IS - 1 SN - 0888-7543, 0888-7543 KW - Bacterial Proteins KW - 0 KW - DNA, Complementary KW - DinB protein, E coli KW - Escherichia coli Proteins KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - UmuC protein, E coli KW - 98059-80-4 KW - DNA polymerase iota KW - EC 2.7.7.- KW - Nucleotidyltransferases KW - REV1 protein, S cerevisiae KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - Rad30 protein KW - Index Medicus KW - Space life sciences KW - Non-programmatic KW - Phylogeny KW - Animals KW - Bacterial Proteins -- genetics KW - Testis -- metabolism KW - DNA, Complementary -- genetics KW - Humans KW - Gene Expression KW - DNA, Complementary -- isolation & purification KW - Mice KW - Amino Acid Sequence KW - Chromosomes, Human, Pair 18 -- genetics KW - Fungal Proteins -- genetics KW - Sequence Analysis, DNA KW - Chromosome Mapping KW - Chromosomes -- genetics KW - Evolution, Molecular KW - In Situ Hybridization KW - Sequence Alignment KW - Molecular Sequence Data KW - DNA, Complementary -- chemistry KW - Sequence Homology, Amino Acid KW - Male KW - Cell Line KW - Saccharomyces cerevisiae -- genetics KW - DNA-Directed DNA Polymerase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69984613?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Novel+human+and+mouse+homologs+of+Saccharomyces+cerevisiae+DNA+polymerase+eta.&rft.au=McDonald%2C+J+P%3BRapi%C4%87-Otrin%2C+V%3BEpstein%2C+J+A%3BBroughton%2C+B+C%3BWang%2C+X%3BLehmann%2C+A+R%3BWolgemuth%2C+D+J%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1999-08-15&rft.volume=60&rft.issue=1&rft.spage=20&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF140501; GENBANK; AF151691 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of a chlorambucil-resistant human ovarian carcinoma cell line overexpressing glutathione S-transferase mu. AN - 69896660; 10413308 AB - Ovarian carcinoma cells 10-fold resistant to the alkylating agent chlorambucil (CBL) were isolated after repeated exposure of the parent cells to gradually escalating concentrations of the drug. The resistant variant, A2780(100), was highly cross-resistant (9-fold) to melphalan and showed lower-level resistance to other cross-linking agents. The resistant A2780(100) cells had almost 5-fold higher glutathione S-transferase (GST) activity than the parental A2780 cells with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. The pi-class GST(s) was the major isoform(s) in both cell lines. However, the resistant A2780(100) cells had at least 11-fold higher GST mu as compared with the parental cells, in which this isoform was barely detectable. A significant induction of GST mu was observed in A2780 cells, but not in the resistant cells, 18 hr after a single exposure to 100 microM CBL. The induction of GST mu by CBL was both time- and concentration-dependent. Assays of the conjugation of CBL with GSH showed that the human mu-class GST had 3.6- and 5.2-fold higher catalytic efficiency relative to the pi- and alpha-class GSTs, respectively. This difference was reflected in the relatively higher (about 6-fold) efficiency of CBL conjugation in A2780(100) cells as compared with the parental cells. These results have demonstrated for the first time a near-linear correlation between CBL resistance and overexpression of mu-class GSTs and suggest that this overexpression maybe responsible, at least in part, for the acquired resistance of ovarian carcinoma cells to CBL, and possibly the other bifunctional alkylating agents. Consistent with this hypothesis, we found evidence for decreased formation of DNA lesions in A2780(100) compared with the drug-sensitive A2780 cells after exposure to CBL. JF - Biochemical pharmacology AU - Horton, J K AU - Roy, G AU - Piper, J T AU - Van Houten, B AU - Awasthi, Y C AU - Mitra, S AU - Alaoui-Jamali, M A AU - Boldogh, I AU - Singhal, S S AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. horton1@niehs.nih.gov Y1 - 1999/08/15/ PY - 1999 DA - 1999 Aug 15 SP - 693 EP - 702 VL - 58 IS - 4 SN - 0006-2952, 0006-2952 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Isoenzymes KW - Chlorambucil KW - 18D0SL7309 KW - Glutathione Transferase KW - EC 2.5.1.18 KW - Index Medicus KW - Inactivation, Metabolic KW - Tumor Cells, Cultured KW - Isoenzymes -- biosynthesis KW - Humans KW - Cell Division -- drug effects KW - Enzyme Induction KW - Drug Resistance, Neoplasm -- physiology KW - Time Factors KW - Isoenzymes -- metabolism KW - Female KW - DNA Damage -- drug effects KW - Catalysis KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Ovarian Neoplasms -- pathology KW - Glutathione Transferase -- metabolism KW - Glutathione Transferase -- biosynthesis KW - Chlorambucil -- metabolism KW - Chlorambucil -- pharmacology KW - Ovarian Neoplasms -- enzymology KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents, Alkylating -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69896660?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Characterization+of+a+chlorambucil-resistant+human+ovarian+carcinoma+cell+line+overexpressing+glutathione+S-transferase+mu.&rft.au=Horton%2C+J+K%3BRoy%2C+G%3BPiper%2C+J+T%3BVan+Houten%2C+B%3BAwasthi%2C+Y+C%3BMitra%2C+S%3BAlaoui-Jamali%2C+M+A%3BBoldogh%2C+I%3BSinghal%2C+S+S&rft.aulast=Horton&rft.aufirst=J&rft.date=1999-08-15&rft.volume=58&rft.issue=4&rft.spage=693&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-02 N1 - Date created - 1999-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intradermal Delivery of IL-12 Naked DNA Induces Systemic NK Cell Activation and Th1 Response In Vivo That Is Independent of Endogenous IL-12 Production AN - 17312610; 4588609 AB - In this study four murine IL-12 naked DNA expression plasmids (pIL-12), containing both the p35 and p40 subunits, were shown to induce systemic biological effects in vivo after intradermal injection. Three of the four IL-12 expression vectors augmented NK activity and induced expression of the IFN- gamma and IFN- gamma -inducible Mig genes. Both IL-12 p70 heterodimer and IFN- gamma proteins were documented in the serum within 24 h after intradermal injection of the pIL-12o super(-) plasmid, which also induced the highest level of NK activity in the spleen and liver among the IL-12 constructs. Interestingly, both p40 mRNA expression at the injection site and serum protein levels followed a biphasic pattern of expression, with peaks on days 1 and 5. Subsequent studies revealed that the ability of intradermally injected pIL-12o super(-) to augment NK lytic activity was prevented by administration of a neutralizing anti-IL-12 mAb. Finally, injection of the pIL-12o super(-) into BALB/c IL-12 p40 super(-/-) mice also resulted in a biphasic pattern of IL-12 p70 appearance in the serum, and induced IFN- gamma protein and activated NK lytic activity in liver and spleen. These results demonstrate that injection of delivered naked DNA encoding the IL-12 gene mediates the biphasic systemic production of IL-12-inducible genes and augments the cytotoxic function of NK cells in lymphoid and parenchymal organs as a direct result of transgene expression. The results also suggest that these naked DNA plasmids may be useful adjuvants for vaccines against infectious and neoplastic diseases. JF - Journal of Immunology AU - Watanabe, M AU - Fenton, R G AU - Wigginton, J M AU - McCormick, K L AU - Volker, K M AU - Fogler, W E AU - Roessler, P G AU - Wiltrout, R H AD - Experimental Therapeutics Section, Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Building 560, Room 31-93, Frederick, MD 21702-1201, USA, wiltroutr@mail.ncifcrf.gov Y1 - 1999/08/15/ PY - 1999 DA - 1999 Aug 15 SP - 1943 EP - 1950 VL - 163 IS - 4 SN - 0022-1767, 0022-1767 KW - DNA vaccines KW - immunology KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Natural killer cells KW - Adjuvants KW - Interleukin 12 KW - Vaccines KW - F 06807:Active immunization KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17312610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Intradermal+Delivery+of+IL-12+Naked+DNA+Induces+Systemic+NK+Cell+Activation+and+Th1+Response+In+Vivo+That+Is+Independent+of+Endogenous+IL-12+Production&rft.au=Watanabe%2C+M%3BFenton%2C+R+G%3BWigginton%2C+J+M%3BMcCormick%2C+K+L%3BVolker%2C+K+M%3BFogler%2C+W+E%3BRoessler%2C+P+G%3BWiltrout%2C+R+H&rft.aulast=Watanabe&rft.aufirst=M&rft.date=1999-08-15&rft.volume=163&rft.issue=4&rft.spage=1943&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adjuvants; Natural killer cells; Interleukin 12; Vaccines ER - TY - JOUR T1 - VIP and D-ala-peptide T-amide release chemokines which prevent HIV-1 GP120-induced neuronal death. AN - 69957234; 10446313 AB - Vasoactive intestinal peptide (VIP) and DAPTA (D-ala(1)-peptide T-amide, a gp120-derived octapeptide homologous to VIP) prevent neuronal cell death produced by five variants of HIV-1 (human immunodeficiency virus) envelope protein (gp120). VIP or DAPTA treatment of astrocyte cultures resulted in the release of macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES, beta chemokines known to block gp120 interactions with microglial chemokine receptors. In rat cerebral cortical cultures, gp120-induced neuronal killing was partially or completely prevented by chemokines that stimulate the CXCR4, CCR3 or CCR5 chemokine receptors. Chemokines exhibited marked differences in potency and efficacy in preventing toxicity associated with five gp120 variants (LAV/BRU, CM243, RF, SF2, and MN). RANTES had the broadest and most potent inhibition (IC(50)<3 pM for RF isolate). An octapeptide derived from RANTES also exhibited neuroprotection from gp120 (RF isolate) toxicity (IC(50)=0.3 microM). Treatment with chemokines alone had no detectable effect on neuronal cell number. However, antiserum to MIP-1alpha produced neuronal cell death that was prevented by co-treatment with MIP-1alpha, suggesting that this endogenous chemokine exerts a tonic regulation important to neuronal survival. The neuroprotective action of VIP on gp120 was attenuated by co-treatment with anti-MIP-1alpha. These studies suggest that the neuroprotective action of VIP is linked in part to its release of MIP-1alpha. Furthermore, neuroprotection produced by chemokines is dependent on both the type of chemokine and the variant structure of gp120 and may be relevant to drug strategies for the treatment of AIDS dementia. Copyright 1999 Published by Elsevier Science B.V. JF - Brain research AU - Brenneman, D E AU - Hauser, J AU - Spong, C Y AU - Phillips, T M AU - Pert, C B AU - Ruff, M AD - Section on Developmental and Molecular Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. dbrenn@codon.nih.gov Y1 - 1999/08/14/ PY - 1999 DA - 1999 Aug 14 SP - 27 EP - 36 VL - 838 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Chemokine CCL5 KW - 0 KW - Chemokines KW - HIV Envelope Protein gp120 KW - Neurotoxins KW - Peptide T KW - 106362-33-8 KW - peptide T amide KW - 113021-67-3 KW - Vasoactive Intestinal Peptide KW - 37221-79-7 KW - Index Medicus KW - AIDS/HIV KW - Rats KW - Genetic Variation KW - Animals KW - Cells, Cultured KW - Neurotoxins -- genetics KW - Cell Death -- drug effects KW - Chemokine CCL5 -- analysis KW - Vasoactive Intestinal Peptide -- pharmacology KW - Peptide T -- pharmacology KW - Neurons -- drug effects KW - HIV Envelope Protein gp120 -- genetics KW - HIV KW - Chemokines -- secretion KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69957234?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=VIP+and+D-ala-peptide+T-amide+release+chemokines+which+prevent+HIV-1+GP120-induced+neuronal+death.&rft.au=Brenneman%2C+D+E%3BHauser%2C+J%3BSpong%2C+C+Y%3BPhillips%2C+T+M%3BPert%2C+C+B%3BRuff%2C+M&rft.aulast=Brenneman&rft.aufirst=D&rft.date=1999-08-14&rft.volume=838&rft.issue=1-2&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-07 N1 - Date created - 1999-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oligomerization of a MutS Mismatch Repair Protein from Thermus aquaticus AN - 17282682; 4576068 AB - The MutS DNA mismatch protein recognizes heteroduplex DNAs containing mispaired or unpaired bases. We have examined the oligomerization of a MutS protein from Thermus aquaticus that binds to heteroduplex DNAs at elevated temperatures. Analytical gel filtration, cross- linking of MutS protein with disuccinimidyl suberate, light scattering, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry establish that the Taq protein is largely a dimer in free solution. Analytical equilibrium sedimentation showed that the oligomerization of Taq MutS involves a dimer-tetramer equilibrium in which dimer predominates at concentrations below 10 mu M. The Delta G super(0) sub(2-4) for the dimer to tetramer transition is approximately -6.9 plus or minus 0.1 kcal/mol of tetramer. Analytical gel filtration of native complexes and gel mobility shift assays of an maltose-binding protein-MutS fusion protein bound to a short, 37-base pair heteroduplex DNA reveal that the protein binds to DNA as a dimer with no change in oligomerization upon DNA binding. JF - Journal of Biological Chemistry AU - Biswas, I AU - Ban, C AU - Fleming, K G AU - Qin, J AU - Lary, J W AU - Yphantis, DA AU - Yang, W AU - Hsieh, P AD - Genetics and Biochemistry Branch, Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 1999/08/13/ PY - 1999 DA - 1999 Aug 13 SP - 23673 EP - 23678 VL - 274 IS - 33 SN - 0021-9258, 0021-9258 KW - MutS protein KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-binding protein KW - Oligomerization KW - Thermus aquaticus KW - DNA repair KW - J 02725:DNA KW - N 14652:DNA repair UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Oligomerization+of+a+MutS+Mismatch+Repair+Protein+from+Thermus+aquaticus&rft.au=Biswas%2C+I%3BBan%2C+C%3BFleming%2C+K+G%3BQin%2C+J%3BLary%2C+J+W%3BYphantis%2C+DA%3BYang%2C+W%3BHsieh%2C+P&rft.aulast=Biswas&rft.aufirst=I&rft.date=1999-08-13&rft.volume=274&rft.issue=33&rft.spage=23673&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Thermus aquaticus; Oligomerization; DNA repair; DNA-binding protein ER - TY - JOUR T1 - Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1. AN - 69951842; 10441116 AB - Two variants of human class pi glutathione (GSH) S-transferase 1-1 with either isoleucine or valine in position 104 (hGSTP1-1[I104] and hGSTP1-1[V104]) have distinct activity toward (+)-anti-7, 8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. To elucidate their structure-function relationship, we determined the crystal structures of the two variants in complex with GSBpd, the GSH conjugate of (+)-anti-BPDE, at 2.1 and 2.0 A resolution, respectively. The crystal structures reveal that residue 104 in the xenobiotic substrate-binding site (H-site) dictates the binding modes of the product molecule GSBpd with the following three consequences. First, the distance between the hydroxyl group of Y7 and the sulfur atom of GSBpd is 5.9 A in the hGSTP1-1[I104].GSBpd complex versus 3.2 A in the V104 variant. Second, one of the hydroxyl groups of GSBpd forms a direct hydrogen bond with R13 in hGSTP1-1[V104].GSBpd; in contrast, this hydrogen bond is not observed in the I104 complex. Third, in the hydrophilic portion of the H-site of the I104 complex, five H-site water molecules [Ji, X., et al. (1997) Biochemistry 36, 9690-9702] are observed, whereas in the V104 complex, two of the five have been displaced by the Bpd moiety of GSBpd. Although there is no direct hydrogen bond between Y108 (OH) and the hydroxyl groups of GSBpd, indirect hydrogen bonds mediated by water molecules are observed in both complexes, supporting the previously suggested role of the hydroxyl group of Y108 as an electrophilic participant in the addition of GSH to epoxides. JF - Biochemistry AU - Ji, X AU - Blaszczyk, J AU - Xiao, B AU - O'Donnell, R AU - Hu, X AU - Herzog, C AU - Singh, S V AU - Zimniak, P AD - ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. jix@ncifcrf.gov Y1 - 1999/08/10/ PY - 1999 DA - 1999 Aug 10 SP - 10231 EP - 10238 VL - 38 IS - 32 SN - 0006-2960, 0006-2960 KW - Alkanesulfonic Acids KW - 0 KW - Isoenzymes KW - Morpholines KW - Xenobiotics KW - Water KW - 059QF0KO0R KW - 2-(N-morpholino)ethanesulfonic acid KW - 2GNK67Q0C4 KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide KW - 55097-80-8 KW - GSTP1 protein, human KW - EC 2.5.1.18 KW - Glutathione S-Transferase pi KW - Glutathione Transferase KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Crystallization KW - Stereoisomerism KW - Models, Molecular KW - Glutathione -- metabolism KW - Humans KW - Morpholines -- chemistry KW - Alkanesulfonic Acids -- chemistry KW - Alkanesulfonic Acids -- metabolism KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- chemistry KW - Structure-Activity Relationship KW - Binding Sites KW - 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide -- metabolism KW - Glutathione -- chemistry KW - Crystallography, X-Ray KW - Substrate Specificity KW - Morpholines -- metabolism KW - Protein Conformation KW - Isoenzymes -- chemistry KW - Water -- metabolism KW - Xenobiotics -- metabolism KW - Water -- chemistry KW - Glutathione Transferase -- metabolism KW - Glutathione Transferase -- chemistry KW - Xenobiotics -- chemistry KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69951842?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Structure+and+function+of+residue+104+and+water+molecules+in+the+xenobiotic+substrate-binding+site+in+human+glutathione+S-transferase+P1-1.&rft.au=Ji%2C+X%3BBlaszczyk%2C+J%3BXiao%2C+B%3BO%27Donnell%2C+R%3BHu%2C+X%3BHerzog%2C+C%3BSingh%2C+S+V%3BZimniak%2C+P&rft.aulast=Ji&rft.aufirst=X&rft.date=1999-08-10&rft.volume=38&rft.issue=32&rft.spage=10231&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-08 N1 - Date created - 1999-09-08 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 4PGT; PDB; 3PGT N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the humoral and cellular immune responses against hepatitis C virus core induced by DNA-based immunization AN - 17315130; 4588516 AB - Hepatitis C Virus (HCV) causes most cases of posttransfusion hepatitis. Chronic HCV infection is highly related to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Current therapies are only minimally effective and no vaccine has been developed. DNA-based immunization could be of prophylactic and therapeutic value for HCV infection. By intramuscular inoculation in BALB/c mice with an HCV recombinant plasmid pCI-HCV-C, we found significant levels of IgM antibody, but no significant IgG rise. After boost the immunized mice with recombinant HCV-core protein (cp1-10; 1-164aa), the anticore IgG, verified by Western-blotting, rose rapidly, which was two weeks earlier than that with control plasmid. Spleen cells from pCI-HCV-C immunized mice gave higher proliferation index (PI) than control (P < 0.05). The PI of cp1-10 boosted mice was even higher. Proliferation blocking assay with mAb proved the responding cell to be of CD4 super(+)CD8 super(-) phenotype, supporting specific priming of T helper cells. A super(51)Cr-releasing CTL assay specific for HCV-core was developed, and a specific CTL response against HCV-core was demonstrated in both pCI-HCV-C immunized mice and mice boosted with cp1-10. Strong cytotoxic activity against peptide-pulsed p815 cells (H-2 super(d)), but not EL-4 cells (H-2 super(b)), suggested MHC class I restriction of the CTL activity. Blocking of CTL with mAb proved the effector cells to be of CD4 super(-)CD8 super(+). Three CTL epitopes in HCV-core protein were demonstrated. We failed to detect CTL when immunized only with core protein. The results suggested that vaccination with HCV-core derived DNA sequences could be an effective method to induce humoral and cellular immune responses to HCV. JF - Vaccine AU - Hu, G-J AU - Wang, RY-H AU - Han, D-S AU - Alter, HJ AU - Shih, JW-K AD - Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1184, USA, jshih@dtm.cc.nih.gov Y1 - 1999/08/06/ PY - 1999 DA - 1999 Aug 06 SP - 3160 EP - 3170 VL - 17 IS - 23-24 SN - 0264-410X, 0264-410X KW - DNA vaccines KW - hepatitis C virus KW - immunology KW - mice KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immune response (cell-mediated) KW - Hepatitis C virus KW - Vaccines KW - Immune response (humoral) KW - Hepatocellular carcinoma KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17315130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=Characterization+of+the+humoral+and+cellular+immune+responses+against+hepatitis+C+virus+core+induced+by+DNA-based+immunization&rft.au=Hu%2C+G-J%3BWang%2C+RY-H%3BHan%2C+D-S%3BAlter%2C+HJ%3BShih%2C+JW-K&rft.aulast=Hu&rft.aufirst=G-J&rft.date=1999-08-06&rft.volume=17&rft.issue=23-24&rft.spage=3160&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis C virus; Hepatocellular carcinoma; Immune response (humoral); Immune response (cell-mediated); Vaccines ER - TY - JOUR T1 - Comparative characterisation of Russell's viper (Daboia/Vipera russelli) venoms from different regions of the Indian peninsula. AN - 69940843; 10434030 AB - Russell's viper (Daboia/Vipera russelli) venom from different regions of India was subjected to chromatographic, electrophoretic, biochemical and immunological analysis. The elution profiles from ion-exchange chromatography and protein banding pattern from SDS-PAGE showed a significant variation in the constituents of venoms. The acidic proteins are found to be predominant in the venoms of eastern and western regions while basic proteins are the major contributors of the northern and southern regional venoms. The major variation of phospholipases A(2) in the venom samples of India may be described as: southern regional venom is rich in basic, toxic PLA(2) while this activity showed a dramatic decrease as one moves towards west, north and eastern regions of India. In addition, the caseinolytic, TAME-hydrolytic, anticoagulant, oedema-inducing and haemorrhagic activities of the venoms have also varied from one region to another. The muscle specimens of mice injected with venoms of different regions showed variable change in the muscle fibre damage and cell morphology. The eastern regional venom is most lethal among all the venoms. The lethal potencies for four regional venoms vary as: eastern>western>southern>northern. The polyclonal antibodies prepared against the venom of southern region showed cross-reaction with the venoms of other regions, but the extent of cross-reaction and diffusion patterns are different. However, the polyclonal antibodies prepared against southern regional venom showed no protection against lethal toxicity of other regional venoms. JF - Biochimica et biophysica acta AU - Prasad, N B AU - Uma, B AU - Bhatt, S K AU - Gowda, V T AD - Department of Studies in Biochemistry, University of Mysore, Mysore 570006, India. nprasad@nhgri.nih.gov Y1 - 1999/08/05/ PY - 1999 DA - 1999 Aug 05 SP - 121 EP - 136 VL - 1428 IS - 2-3 SN - 0006-3002, 0006-3002 KW - Antivenins KW - 0 KW - Protease Inhibitors KW - Proteins KW - Trypsin Inhibitors KW - Viper Venoms KW - Esterases KW - EC 3.1.- KW - Index Medicus KW - Muscle, Skeletal -- pathology KW - Animals KW - Blood Coagulation Tests KW - Electrophoresis, Polyacrylamide Gel KW - Chromatography, Ion Exchange KW - Mice KW - Skin Diseases -- pathology KW - Hemorrhage -- etiology KW - India KW - Trypsin Inhibitors -- chemistry KW - Protease Inhibitors -- chemistry KW - Necrosis KW - Antivenins -- immunology KW - Esterases -- antagonists & inhibitors KW - Skin Diseases -- etiology KW - Lethal Dose 50 KW - Geography KW - Edema -- etiology KW - Proteins -- chemistry KW - Russell's Viper KW - Viper Venoms -- toxicity KW - Viper Venoms -- immunology KW - Viper Venoms -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69940843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Comparative+characterisation+of+Russell%27s+viper+%28Daboia%2FVipera+russelli%29+venoms+from+different+regions+of+the+Indian+peninsula.&rft.au=Prasad%2C+N+B%3BUma%2C+B%3BBhatt%2C+S+K%3BGowda%2C+V+T&rft.aulast=Prasad&rft.aufirst=N&rft.date=1999-08-05&rft.volume=1428&rft.issue=2-3&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-27 N1 - Date created - 1999-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the genotoxicity of anthraquinones in mammalian cells. AN - 69940148; 10434060 AB - Naturally occurring 1,8-dihydroxyanthraquinones are under consideration as possible carcinogens. Here we wanted to elucidate a possible mechanism of their genotoxicity. All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine. In a cell-free decatenation assay, emodin exerted a stronger, danthron a similar and aloe-emodin a weaker inhibition of topoisomerase II activity than m-amsacrine. Analysis of the chromosomal extent of DNA damage induced by these anthraquinones was performed in mouse lymphoma L5178Y cells. Anthraquinone-induced mutant cell clones showed similar chromosomal lesions when compared to the topoisomerase II inhibitors etoposide and m-amsacrine, but were different from mutants induced by the DNA alkylator ethyl methanesulfonate. These data support the idea that inhibition of the catalytic activity of topoisomerase II contributes to anthraquinone-induced genotoxicity and mutagenicity. JF - Biochimica et biophysica acta AU - Mueller, S O AU - Stopper, H AD - Department of Toxicology, University of Würzburg, 97078, Würzburg, Germany. mueller1@niehs.nih.gov Y1 - 1999/08/05/ PY - 1999 DA - 1999 Aug 05 SP - 406 EP - 414 VL - 1428 IS - 2-3 SN - 0006-3002, 0006-3002 KW - Anthraquinones KW - 0 KW - Benzimidazoles KW - Fluorescent Dyes KW - Topoisomerase II Inhibitors KW - aloe emodin KW - C8IYT9CR7C KW - Emodin KW - KA46RNI6HN KW - bisbenzimide ethoxide trihydrochloride KW - P976261J69 KW - danthron KW - Z4XE6IBF3V KW - Index Medicus KW - Molecular Structure KW - Emodin -- analogs & derivatives KW - Animals KW - Mutagenicity Tests KW - Tumor Cells, Cultured KW - Plants, Medicinal KW - Polymerase Chain Reaction -- methods KW - Electrophoresis, Agar Gel KW - Leukemia L5178 KW - Emodin -- toxicity KW - Aloe -- chemistry KW - Anthraquinones -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69940148?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochimica+et+biophysica+acta&rft.atitle=Characterization+of+the+genotoxicity+of+anthraquinones+in+mammalian+cells.&rft.au=Mueller%2C+S+O%3BStopper%2C+H&rft.aulast=Mueller&rft.aufirst=S&rft.date=1999-08-05&rft.volume=1428&rft.issue=2-3&rft.spage=406&rft.isbn=&rft.btitle=&rft.title=Biochimica+et+biophysica+acta&rft.issn=00063002&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-27 N1 - Date created - 1999-09-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A vital role for glycosphingolipid synthesis during development and differentiation. AN - 69930767; 10430909 AB - Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many cell membrane events, including cellular interactions, signaling, and trafficking. We have investigated their roles in development and differentiation by eliminating the major synthesis pathway of GSLs through targeted disruption of the Ugcg gene encoding glucosylceramide synthase. In the absence of GSL synthesis, embryogenesis proceeded well into gastrulation with differentiation into primitive germ layers and patterning of the embryo but was abruptly halted by a major apoptotic process. In vivo, embryonic stem cells deficient in GSL synthesis were again able to differentiate into endodermal, mesodermal, and ectodermal derivatives but were strikingly deficient in their ability to form well differentiated tissues. In vitro, however, hematopoietic and neuronal differentiation could be induced. The results demonstrate that the synthesis of GSL structures is essential for embryonic development and for the differentiation of some tissues and support the concept that GSLs are involved in crucial cell interactions mediating these processes. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Yamashita, T AU - Wada, R AU - Sasaki, T AU - Deng, C AU - Bierfreund, U AU - Sandhoff, K AU - Proia, R L AD - Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/08/03/ PY - 1999 DA - 1999 Aug 03 SP - 9142 EP - 9147 VL - 96 IS - 16 SN - 0027-8424, 0027-8424 KW - Glycosphingolipids KW - 0 KW - Glucosyltransferases KW - EC 2.4.1.- KW - ceramide glucosyltransferase KW - EC 2.4.1.80 KW - Index Medicus KW - Teratoma -- genetics KW - Animals KW - Embryo, Mammalian -- physiology KW - Apoptosis KW - Stem Cells -- pathology KW - Cell Differentiation -- genetics KW - Mice KW - Genomic Library KW - Embryo, Mammalian -- pathology KW - Mice, Knockout KW - Genotype KW - In Situ Nick-End Labeling KW - Polymerase Chain Reaction KW - In Situ Hybridization KW - Teratoma -- pathology KW - Gastrula -- physiology KW - Glycosphingolipids -- physiology KW - Glycosphingolipids -- biosynthesis KW - Embryonic and Fetal Development -- genetics KW - Glucosyltransferases -- metabolism KW - Embryonic and Fetal Development -- physiology KW - Glucosyltransferases -- genetics KW - Glucosyltransferases -- deficiency KW - Gastrula -- cytology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69930767?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+vital+role+for+glycosphingolipid+synthesis+during+development+and+differentiation.&rft.au=Yamashita%2C+T%3BWada%2C+R%3BSasaki%2C+T%3BDeng%2C+C%3BBierfreund%2C+U%3BSandhoff%2C+K%3BProia%2C+R+L&rft.aulast=Yamashita&rft.aufirst=T&rft.date=1999-08-03&rft.volume=96&rft.issue=16&rft.spage=9142&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Development. 1997 Jan;124(2):279-87 [9053305] Anat Histol Embryol. 1996 Dec;25(4):289-94 [9011106] Nature. 1997 Jun 5;387(6633):569-72 [9177342] Curr Opin Cell Biol. 1997 Aug;9(4):534-42 [9261060] Mol Biol Cell. 1997 Dec;8(12):2365-78 [9398661] Mech Dev. 1997 Nov;68(1-2):3-25 [9431800] Biochem Soc Trans. 1997 Nov;25(4):1171-5 [9449970] Brain Pathol. 1998 Jan;8(1):79-100 [9458169] Development. 1998 Apr;125(8):1529-39 [9502734] Annu Rev Physiol. 1998;60:643-65 [9558480] Proc Natl Acad Sci U S A. 1998 May 26;95(11):6198-203 [9600941] Development. 1998 Aug;125(16):3015-25 [9671576] J Biol Chem. 1998 Jul 31;273(31):19634-8 [9677390] Trends Cell Biol. 1998 Jan;8(1):29-33 [9695805] Trends Cell Biol. 1998 May;8(5):198-202 [9695839] Nat Genet. 1998 Aug;19(4):348-55 [9697695] Annu Rev Biochem. 1998;67:199-225 [9759488] Glycobiology. 1998 Oct;8(10):xi-xix [9840984] J Biol Chem. 1998 Dec 11;273(50):33766-73 [9837965] J Biol Chem. 1999 Jan 1;274(1):451-6 [9867864] J Clin Invest. 1999 Feb;103(4):497-505 [10021458] Science. 1985 May 10;228(4700):745-7 [2581316] Cell. 1988 Jul 15;54(2):235-45 [3292056] J Biol Chem. 1989 Jun 5;264(16):9476-84 [2470757] Science. 1989 Jun 16;244(4910):1288-92 [2660260] J Biol Chem. 1990 Nov 5;265(31):18713-6 [2229037] Cell. 1991 Apr 5;65(1):65-74 [1826463] Biochem J. 1991 Dec 1;280 ( Pt 2):295-302 [1747103] J Cell Biol. 1992 Apr;117(2):259-67 [1532799] Development. 1991 Dec;113(4):1105-14 [1811930] Glycobiology. 1991 Nov;1(5):477-85 [1822229] Nucleic Acids Res. 1992 Aug 11;20(15):3815-20 [1508665] Glycobiology. 1993 Apr;3(2):97-130 [8490246] Adv Lipid Res. 1993;25:235-67 [8368150] Prog Brain Res. 1994;101:XI-XIV [8029441] Prog Brain Res. 1994;101:119-26 [8029445] Genes Dev. 1994 Oct 15;8(20):2466-77 [7958910] Genes Dev. 1994 Dec 15;8(24):3045-57 [8001823] Dev Biol. 1995 Apr;168(2):342-57 [7729574] Development. 1994 Oct;120(10):2979-89 [7607086] Nat Genet. 1995 Oct;11(2):155-63 [7550343] Cell. 1995 Oct 20;83(2):279-87 [7585945] Cell. 1996 Mar 22;84(6):911-21 [8601314] J Cell Biol. 1996 May;133(3):695-708 [8636242] J Biochem. 1995 Dec;118(6):1091-103 [8720120] FASEB J. 1996 Oct;10(12):1388-97 [8903509] Cell. 1997 Feb 7;88(3):347-54 [9039261] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis AN - 17326713; 4576276 AB - With cDNA microarrays, it is now possible to compare the expression of many genes simultaneously. To maximize the likelihood of finding genes whose expression is altered under the experimental conditions, it would be advantageous to be able to select clones for tissue-appropriate cDNA sets. We have taken advantage of the extensive sequence information in the dbEST expressed sequence tag (EST) database to identify a neural crest-derived melanocyte cDNA set for microarray analysis. Analysis of characterized genes with dbEST identified one library that contained ESTs representing 21 neural crest-expressed genes (library 198). The distribution of the ESTs corresponding to these genes was biased toward being derived from library 198. This is in contrast to the EST distribution profile for a set of control genes characterized to be more ubiquitously expressed in multiple tissues (P < 1 x 10 super(-9)). From library 198, a subset of 852 clustered ESTs were selected that have a library distribution profile similar to that of the 21 neural crest-expressed genes. Microarray analysis demonstrated the majority of the neural crest-selected 852 ESTs (Mel1 array) were differentially expressed in melanoma cell lines compared with a non-neural crest kidney epithelial cell line (P < 1 x 10 super(-8)). This was not observed with an array of 1,238 ESTs that was selected without library origin bias (P = 0.204). This study presents an approach for selecting tissue- appropriate cDNAs that can be used to examine the expression profiles of developmental processes and diseases. JF - Proceedings of the National Academy of Sciences, USA AU - Loftus, S K AU - Chen, Y AU - Gooden, G AU - Ryan, J F AU - Birznieks, G AU - Hilliard, M AU - Baxevanis, AD AU - Bittner, M AU - Meltzer, P AU - Trent, J AU - Pavan, W AD - Genetic Disease Research Branch, Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892 USA, bpavan@nhgri.nih.gov Y1 - 1999/08/03/ PY - 1999 DA - 1999 Aug 03 SP - 9277 EP - 9280 VL - 96 IS - 16 SN - 0027-8424, 0027-8424 KW - DNA microarrays KW - Expressed sequence tags KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Genetics Abstracts KW - Melanocytes KW - Neural crest KW - Melanoma KW - G 07381:General KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17326713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Informatic+selection+of+a+neural+crest-melanocyte+cDNA+set+for+microarray+analysis&rft.au=Loftus%2C+S+K%3BChen%2C+Y%3BGooden%2C+G%3BRyan%2C+J+F%3BBirznieks%2C+G%3BHilliard%2C+M%3BBaxevanis%2C+AD%3BBittner%2C+M%3BMeltzer%2C+P%3BTrent%2C+J%3BPavan%2C+W&rft.aulast=Loftus&rft.aufirst=S&rft.date=1999-08-03&rft.volume=96&rft.issue=16&rft.spage=9277&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.16.9277 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Melanocytes; Neural crest DO - http://dx.doi.org/10.1073/pnas.96.16.9277 ER - TY - JOUR T1 - Homologue scanning mutagenesis reveals CD66 receptor residues required for neisserial Opa protein binding. AN - 69933071; 10430622 AB - The immunoglobulin-like family of CD66 antigens, present on human neutrophils and epithelial cells, are used as receptors for adhesins expressed by the pathogenic Neisseriae. N. gonorrhoeae strain MS11 can express 11 isoforms of these adhesins, called opacity-related (Opa) proteins. Each MS11 Opa protein recognizes a distinct spectrum of CD66 receptors. CD66-Opa binding is mediated by the NH(2)-terminal domain of the receptor and occurs through protein-protein interactions. In this report, we have investigated the molecular basis for the binding between the CD66 and Opa protein families by mapping amino acids in CD66 receptors that determine Opa protein binding. We performed homologue scanning mutagenesis between CD66e, which binds multiple Opa variants, and CD66b, which binds none, and tested both loss-of-function by CD66e and gain-of-function by CD66b in solution assays and in assays involving full-length receptors expressed by epithelial cells. We found that three residues in the CD66e N-domain are required for maximal Opa protein receptor activity. Opa proteins that recognize the same spectrum of native CD66 molecules showed differential binding of receptors with submaximal activity, indicating that the binding characteristics of these Opa proteins are actually slightly different. These data provide a first step toward resolving the structural requirements for Opa-CD66 interaction. JF - The Journal of experimental medicine AU - Bos, M P AU - Hogan, D AU - Belland, R J AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840-2999, USA. Martine_bos@nih.gov Y1 - 1999/08/02/ PY - 1999 DA - 1999 Aug 02 SP - 331 EP - 340 VL - 190 IS - 3 SN - 0022-1007, 0022-1007 KW - Antigens, Bacterial KW - 0 KW - Antigens, CD KW - Antigens, Differentiation KW - Bacterial Outer Membrane Proteins KW - CD66 antigens KW - Cell Adhesion Molecules KW - Peptide Fragments KW - opacity proteins KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Peptide Mapping KW - Peptide Fragments -- genetics KW - Epithelial Cells -- microbiology KW - Bacterial Outer Membrane Proteins -- metabolism KW - Amino Acid Sequence KW - Peptide Fragments -- physiology KW - Epithelial Cells -- metabolism KW - Peptide Fragments -- chemistry KW - Transfection KW - Molecular Sequence Data KW - CHO Cells KW - Protein Binding -- genetics KW - Cricetinae KW - Mutagenesis, Site-Directed KW - Antigens, CD -- biosynthesis KW - Antigens, CD -- physiology KW - Neisseria gonorrhoeae -- metabolism KW - Antigens, Bacterial -- metabolism KW - Neisseria gonorrhoeae -- physiology KW - Antigens, Differentiation -- metabolism KW - Antigens, Differentiation -- genetics KW - Antigens, Differentiation -- biosynthesis KW - Antigens, CD -- metabolism KW - Antigens, CD -- genetics KW - Antigens, Differentiation -- physiology KW - Sequence Homology, Amino Acid UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69933071?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Homologue+scanning+mutagenesis+reveals+CD66+receptor+residues+required+for+neisserial+Opa+protein+binding.&rft.au=Bos%2C+M+P%3BHogan%2C+D%3BBelland%2C+R+J&rft.aulast=Bos&rft.aufirst=M&rft.date=1999-08-02&rft.volume=190&rft.issue=3&rft.spage=331&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Exp Med. 1995 Nov 1;182(5):1231-41 [7595194] Science. 1995 Sep 1;269(5228):1273-8 [7544493] Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14851-6 [8962144] Mol Microbiol. 1996 Dec;22(5):941-50 [8971715] Biochem J. 1996 Dec 15;320 ( Pt 3):847-53 [9003371] J Exp Med. 1997 May 5;185(9):1557-64 [9151893] Infect Immun. 1997 Jun;65(6):2353-61 [9169774] Curr Opin Cell Biol. 1997 Oct;9(5):616-26 [9330864] Br J Haematol. 1997 Sep;98(3):612-20 [9332316] Mol Microbiol. 1997 Dec;26(5):971-80 [9426134] Biochem Biophys Res Commun. 1998 Jan 6;242(1):79-83 [9439613] Microbiology. 1998 Jan;144 ( Pt 1):157-66 [9467908] J Bacteriol. 1998 Mar;180(5):1323-30 [9495774] Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9584-9 [9689124] Immunol Rev. 1998 Jun;163:197-215 [9700512] Immunol Rev. 1998 Jun;163:217-36 [9700513] Folia Microbiol (Praha). 1998;43(3):311-9 [9717259] J Exp Med. 1988 Dec 1;168(6):2121-9 [3143800] Mol Microbiol. 1988 Nov;2(6):797-806 [3145386] Cell. 1989 Feb 24;56(4):539-47 [2492905] Infect Immun. 1978 Jan;19(1):320-31 [415006] Mol Microbiol. 1988 Mar;2(2):227-36 [2454382] Science. 1989 Mar 10;243(4896):1330-6 [2466339] Cell. 1989 Apr 21;57(2):327-34 [2702691] J Mol Evol. 1989 Aug;29(2):126-34 [2509715] Biochem Biophys Res Commun. 1990 Feb 14;166(3):1063-71 [2306228] Cancer Res. 1990 Oct 15;50(20):6534-9 [2208113] Infect Immun. 1991 Jun;59(6):2051-7 [1674739] J Biol Chem. 1991 Jun 25;266(18):11810-7 [2050678] J Clin Lab Anal. 1991;5(5):344-66 [1941355] Mol Microbiol. 1991 Aug;5(8):1889-901 [1815562] FEBS Lett. 1992 Apr 20;301(2):207-14 [1568482] J Virol. 1993 Jan;67(1):1-8 [8380065] EMBO J. 1993 Feb;12(2):641-50 [8440254] Eur J Biochem. 1993 May 15;214(1):27-35 [8508798] Nucleic Acids Res. 1994 Jul 11;22(13):2587-91 [8041621] Methods Enzymol. 1994;236:420-37 [7968627] Trends Biochem Sci. 1994 Sep;19(9):354-8 [7985226] EMBO J. 1995 May 15;14(10):2144-54 [7774572] Protein Sci. 1995 Mar;4(3):521-33 [7795533] J Immunol. 1995 Jul 15;155(2):529-32 [7608533] J Exp Med. 1995 Aug 1;182(2):511-7 [7629509] J Mol Biol. 1996 Jun 21;259(4):718-36 [8683578] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vitro regulation of expression of cartilage-derived morphogenetic proteins by growth hormone and insulinlike growth factor 1 in the bovine cricoid chondrocyte. AN - 85308099; pmid-10448738 AB - OBJECTIVES: To delineate the endogenous growth factors that regulate cricoid cartilage growth at the molecular level. Specifically, to attempt to establish the presence of cartilage-derived morphogenetic proteins (CDMPs), cartilage-specific members of the bone morphogenetic protein family, in newborn bovine cricoid chondrocytes and to assess the expression of these endogenous growth factors with the addition of exogenous growth hormone or insulinlike growth factor 1 in an in vitro chondrocyte culture model. METHODS AND DESIGN: Basic science molecular biologic research methods, including high-density monolayer and explant chondrocyte cultures with extraction of messenger RNA and quantitation via Northern blot hybridization via radiolabeled complementary DNA probes. SETTING: Intramural basic science research laboratory. RESULTS: Both CDMP-1 and CDMP-2 were found in newborn cricoid chondrocytes. Addition of exogenous growth hormone did not appear to influence the expression of CDMP-1 or CDMP-2. Addition of exogenous insulinlike growth factor 1 appeared to down-regulate the expression of CDMP-1 but had no effect on the expression of CDMP-2. No major differences in CDMP level of expression were noted between high-density monolayer cultures vs explant cultures. No tissue specificity differences were noted in regulation of CDMPs between cricoid and articular chondrocytes. CONCLUSIONS: Our preliminary studies indicate the presence of endogenous morphogenetic proteins in newborn bovine cricoid chondrocytes. These novel polypeptide hormones (CDMP-1 and CDMP-2) have not been previously reported in laryngeal cartilage chondrocytes. Change in level of transcription of these morphogenetic proteins under various in vitro conditions suggests that these proteins are subject to regulation and/or play a regulatory role in cricoid chondrocyte growth and differentiation. Further experimentation is needed to confirm these findings. JF - Archives of otolaryngology--head & neck surgery AU - Tomaski, S M AU - Zalzal, G H AD - Craniofacial and Skeletal Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 901 EP - 906 VL - 125 IS - 8 SN - 0886-4470, 0886-4470 KW - Abridged Index Medicus; Index Medicus KW - National Library of Medicine KW - Animals KW - Growth Substances -- genetics KW - Growth Differentiation Factor 5 KW - DNA Probes -- chemistry KW - Blotting, Northern KW - Cricoid Cartilage -- metabolism KW - Cricoid Cartilage -- cytology KW - Growth Substances -- metabolism KW - Animals, Newborn KW - Cattle KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Chondrocytes -- drug effects KW - Chondrocytes -- cytology KW - Bone Morphogenetic Proteins -- metabolism KW - Cricoid Cartilage -- drug effects KW - Gene Expression Regulation KW - Chondrocytes -- metabolism KW - Growth Hormone -- pharmacology KW - Transforming Growth Factor beta -- metabolism KW - Insulin-Like Growth Factor I -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85308099?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+otolaryngology--head+%26+neck+surgery&rft.atitle=In+vitro+regulation+of+expression+of+cartilage-derived+morphogenetic+proteins+by+growth+hormone+and+insulinlike+growth+factor+1+in+the+bovine+cricoid+chondrocyte.&rft.au=Tomaski%2C+S+M%3BZalzal%2C+G+H&rft.aulast=Tomaski&rft.aufirst=S&rft.date=1999-08-01&rft.volume=125&rft.issue=8&rft.spage=901&rft.isbn=&rft.btitle=&rft.title=Archives+of+otolaryngology--head+%26+neck+surgery&rft.issn=08864470&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - ATP-Induced Ca(2+) release in cochlear outer hair cells: localization of an inositol triphosphate-gated Ca(2+) store to the base of the sensory hair bundle. AN - 85270503; pmid-10436049 AB - We used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) evoked by focal applications of extracellular ATP to the hair bundle of outer hair cells (OHCs): the sensory-motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca(2+)](i). After an initial entry of Ca(2+) through the apical membrane, a second and larger, inositol triphosphate (InsP(3))-gated, [Ca(2+)](i) surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca(2+) release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen's body. Using confocal immunofluorescence microscopy, we showed that InsP(3) receptors share this location. Consistent with a Ca(2+)-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G-proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca(2+)](i) rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca(2+)-clearance power of the stereocilia and transiently elevates [Ca(2+)](i) at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechanotransduction. JF - The Journal of Neuroscience AU - Mammano, F AU - Frolenkov, G I AU - Lagostena, L AU - Belyantseva, I A AU - Kurc, M AU - Dodane, V AU - Colavita, A AU - Kachar Bechara AD - Biophysics Sector and Istituto Nazionale di Fisica della Materia Unit, International School for Advanced Studies, 34014 Trieste, Italy.; National Institute on Deafness and Other Communication Disorders PY - 1999 SP - 6918 EP - 6929 VL - 19 IS - 16 SN - 0270-6474, 0270-6474 KW - Video Recording KW - Patch-Clamp Techniques KW - Mechanoreceptors KW - Calcium KW - Inositol 1,4,5-Trisphosphate KW - Guinea Pigs KW - Hair Cells, Outer KW - Animal KW - Support, Non-U.S. Gov't KW - Microscopy, Electron KW - Adenosine Triphosphate KW - Fluorescent Antibody Technique KW - Signal Transduction KW - Ion Channel Gating UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=ATP-Induced+Ca%282%2B%29+release+in+cochlear+outer+hair+cells%3A+localization+of+an+inositol+triphosphate-gated+Ca%282%2B%29+store+to+the+base+of+the+sensory+hair+bundle.&rft.au=Mammano%2C+F%3BFrolenkov%2C+G+I%3BLagostena%2C+L%3BBelyantseva%2C+I+A%3BKurc%2C+M%3BDodane%2C+V%3BColavita%2C+A%3BKachar+Bechara&rft.aulast=Mammano&rft.aufirst=F&rft.date=1999-08-01&rft.volume=19&rft.issue=16&rft.spage=6918&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Introduction--workshop on characterizing the effects of endocrine disruptors on human health at environmental exposure levels. AN - 70870045; 10421769 JF - Environmental health perspectives AU - Melnick, R L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 603 EP - 604 VL - 107 Suppl 4 SN - 0091-6765, 0091-6765 KW - Biomarkers KW - 0 KW - Endocrine Disruptors KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Models, Animal KW - Animals KW - Endocrine System -- growth & development KW - Dose-Response Relationship, Drug KW - Polychlorinated Biphenyls -- toxicity KW - Humans KW - Adult KW - Endocrine System -- drug effects KW - Homeostasis KW - Congresses as Topic KW - Risk Assessment KW - Endocrine Disruptors -- toxicity KW - Environmental Exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70870045?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Introduction--workshop+on+characterizing+the+effects+of+endocrine+disruptors+on+human+health+at+environmental+exposure+levels.&rft.au=Melnick%2C+R+L&rft.aulast=Melnick&rft.aufirst=R&rft.date=1999-08-01&rft.volume=107+Suppl+4&rft.issue=&rft.spage=603&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2009-08-31 N1 - Date created - 2009-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The linoleic acid metabolite, 13-HpODE augments the phosphorylation of EGF receptor and SHP-2 leading to their increased association. AN - 70794326; 10509870 AB - In previous studies with Syrian hamster embryo fibroblasts, we found that a specific lipoxygenase metabolite of linoleic acid, 13(S)-hydroperoxyoctadecadienoic acid (HpODE), enhanced epidermal growth factor (EGF) signal transduction in a tumor suppressor gene plus phenotype (supB+); with a diminished response to 13(S)-HpODE in a tumor suppressor gene minus phenotype (supB-). This differential response was attributed to differences in the rate of EGF receptor (EGFR) dephosphorylation. To further define the molecular basis for these observations, in this report we examine the interaction of phosphorylated EGFR with the SH2 domain-containing protein tyrosine phosphatase, SHP-2, a positive modulator of EGF dependent cell growth. SHP-2 associated with phosphorylated EGFR to a greater extent in supB+ cells when compared to supB-. This differential association could not be accounted for by differences between suppressor gene phenotypes in SHP-2 protein level or mutations in the molecular sequence. The addition of 13(S)-HpODE stimulated a concentration-dependent increase in EGF-dependent phosphorylation of SHP-2 and its association with EGFR. A more dramatic response was observed in the supB+ cells. Differences in SHP-2 interaction with EGFR may account, in part, for phenotypic differences in the growth rates and responsiveness to EGF between the supB+ and supB- cells. EGFR-SHP-2 association appears to play an important role in the regulation of EGFR signal transduction. JF - Prostaglandins, leukotrienes, and essential fatty acids AU - Hui, R AU - Kameda, H AU - Risinger, J I AU - Angerman-Stewart, J AU - Han, B AU - Barrett, J C AU - Eling, T E AU - Glasgow, W C AD - Eicosanoid Biochemistry and Cancer and Aging Sections, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 137 EP - 143 VL - 61 IS - 2 SN - 0952-3278, 0952-3278 KW - Antibodies KW - 0 KW - Intracellular Signaling Peptides and Proteins KW - Linoleic Acids KW - Lipid Peroxides KW - Phosphotyrosine KW - 21820-51-9 KW - 13-hydroperoxy-9,11-octadecadienoic acid KW - 23017-93-8 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - EC 3.1.3.48 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - SH2 Domain-Containing Protein Tyrosine Phosphatases KW - Index Medicus KW - Animals KW - Phosphotyrosine -- immunology KW - Protein Binding KW - src Homology Domains KW - Phosphorylation -- drug effects KW - Phenotype KW - Blotting, Western KW - Genes, Tumor Suppressor -- genetics KW - Cell Line KW - Receptor, Epidermal Growth Factor -- metabolism KW - Protein Tyrosine Phosphatases -- metabolism KW - Lipid Peroxides -- pharmacology KW - Linoleic Acids -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70794326?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.atitle=The+linoleic+acid+metabolite%2C+13-HpODE+augments+the+phosphorylation+of+EGF+receptor+and+SHP-2+leading+to+their+increased+association.&rft.au=Hui%2C+R%3BKameda%2C+H%3BRisinger%2C+J+I%3BAngerman-Stewart%2C+J%3BHan%2C+B%3BBarrett%2C+J+C%3BEling%2C+T+E%3BGlasgow%2C+W+C&rft.aulast=Hui&rft.aufirst=R&rft.date=1999-08-01&rft.volume=61&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=Prostaglandins%2C+leukotrienes%2C+and+essential+fatty+acids&rft.issn=09523278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-20 N1 - Date created - 1999-12-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The anti-carcinogenic role of lycopene, abundantly present in tomato. AN - 70060478; 10493308 AB - Among the many carotenoids present in nature, lycopene has been of special interest and has received attention in recent times due to its suggestive association in reducing risk for cancer at many sites including breast, prostate and pancreas. Several studies have attempted to determine the bioactive levels of this carotenoid in human tissues and the influence of plant food and cancer on carotenoid levels. Experimental studies have also implicated the protective role of lycopene during carcinogenesis. These observations should justify further exploration and evaluation of the biological function of lycopene alone or in combination with other chemical compounds present in tomato fruit for their use in cancer prevention. JF - European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) AU - Sengupta, A AU - Das, S AD - Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 325 EP - 330 VL - 8 IS - 4 SN - 0959-8278, 0959-8278 KW - Anticarcinogenic Agents KW - 0 KW - Carotenoids KW - 36-88-4 KW - lycopene KW - SB0N2N0WV6 KW - Index Medicus KW - Animals KW - Humans KW - Lycopersicon esculentum -- chemistry KW - Carotenoids -- therapeutic use KW - Anticarcinogenic Agents -- therapeutic use KW - Anticarcinogenic Agents -- chemistry KW - Neoplasms -- prevention & control KW - Carotenoids -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70060478?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.atitle=The+anti-carcinogenic+role+of+lycopene%2C+abundantly+present+in+tomato.&rft.au=Sengupta%2C+A%3BDas%2C+S&rft.aulast=Sengupta&rft.aufirst=A&rft.date=1999-08-01&rft.volume=8&rft.issue=4&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=European+journal+of+cancer+prevention+%3A+the+official+journal+of+the+European+Cancer+Prevention+Organisation+%28ECP%29&rft.issn=09598278&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy. AN - 70031951; 10480216 AB - Lymphocytes are believed to play a role in the induction and perpetuation of membranous nephropathy. Fludarabine is a purine nucleoside analog with selective activity against both dividing and resting lymphocytes. We evaluated the tolerance, toxicity, pharmacokinetics, immunologic, and clinical effects of fludarabine in patients with membranous nephropathy in an single arm pilot study. Eight patients with idiopathic (n = 7) or lupus (n = 1) membranous nephropathy who had failed high-dose prednisone (n = 8) and/or alkylating agents (n = 2), or cyclosporine (n = 1) were treated with 6-monthly cycles of fludarabine (cycles 1-2, 20 mg/m2/day x 2 days, cycles 3-6, 20 mg/m2/day x 3 days). Mean proteinuria was 9 g/day with a mean duration of disease of 25 months (range 12-48). Proteinuria, GFR and effective renal plasma flow were compared before and after completing the treatment. Seven patients completed the protocol. CD3, CD4, CD8 and B cell counts decreased by 53%, 46%, 61% and 84%, respectively, at the end of treatment and remained at lower than pretreatment levels 6 months after completing the trial. Despite lymphopenia, serum immunoglobulin levels remained unchanged. Both naive (CD45RA+) and memory CD4+ T cells (CD45RO+) were reduced (naive > memory). Proteinuria decreased by > or = 50% in 5 out of 7 patients (p = 0.11). Filtration fraction improved in all patients with decreased filtration fraction at baseline. The only side-effect observed was one episode of acute bacterial sinusitis that responded promptly to antibiotic therapy. We conclude that low-dose fludarabine treatment in patients with membranous nephropathy is well tolerated and results in significant lymphopenia involving B more than T cells. In this pilot study improvement in proteinuria and filtration rate were observed. Additional studies are required to determine the optimal dose and clinical efficacy of fludarabine. JF - Clinical nephrology AU - Boumpas, D T AU - Tassiulas, I O AU - Fleisher, T A AU - Vaughan, E AU - Piscitelli, S AU - Kim, Y AU - Pucino, F AU - Balow, J E AU - Austin, H A AD - Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 67 EP - 75 VL - 52 IS - 2 SN - 0301-0430, 0301-0430 KW - Alkylating Agents KW - 0 KW - Anti-Inflammatory Agents KW - Immunoglobulin G KW - Immunosuppressive Agents KW - Cyclosporine KW - 83HN0GTJ6D KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - AIDS/HIV KW - Alkylating Agents -- therapeutic use KW - Lymphocyte Count -- drug effects KW - Proteinuria -- urine KW - CD8-Positive T-Lymphocytes -- drug effects KW - Drug Administration Schedule KW - Immunologic Memory -- drug effects KW - Lupus Nephritis KW - Prednisone -- therapeutic use KW - Cyclosporine -- therapeutic use KW - Glomerular Filtration Rate -- drug effects KW - Humans KW - Anti-Inflammatory Agents -- therapeutic use KW - Pilot Projects KW - CD4-Positive T-Lymphocytes -- drug effects KW - Renal Plasma Flow, Effective -- drug effects KW - Immunoglobulin G -- blood KW - B-Lymphocytes -- drug effects KW - Proteinuria -- drug therapy KW - Adult KW - Sinusitis -- microbiology KW - Middle Aged KW - Follow-Up Studies KW - Lymphocytes -- drug effects KW - Male KW - Female KW - Vidarabine -- analogs & derivatives KW - Vidarabine -- pharmacokinetics KW - Glomerulonephritis, Membranous -- drug therapy KW - Vidarabine -- therapeutic use KW - Vidarabine -- administration & dosage KW - Glomerulonephritis, Membranous -- immunology KW - Vidarabine -- adverse effects KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- pharmacokinetics KW - Immunosuppressive Agents -- adverse effects KW - Immunosuppressive Agents -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70031951?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+nephrology&rft.atitle=A+pilot+study+of+low-dose+fludarabine+in+membranous+nephropathy+refractory+to+therapy.&rft.au=Boumpas%2C+D+T%3BTassiulas%2C+I+O%3BFleisher%2C+T+A%3BVaughan%2C+E%3BPiscitelli%2C+S%3BKim%2C+Y%3BPucino%2C+F%3BBalow%2C+J+E%3BAustin%2C+H+A&rft.aulast=Boumpas&rft.aufirst=D&rft.date=1999-08-01&rft.volume=52&rft.issue=2&rft.spage=67&rft.isbn=&rft.btitle=&rft.title=Clinical+nephrology&rft.issn=03010430&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-07 N1 - Date created - 1999-10-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. AN - 70025957; 10475971 AB - A search of the National Cancer Institute's Anti-Neoplastic Drug Screen for compounds with an inhibitory profile similar to that of the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 yielded anthrax lethal toxin. Anthrax lethal factor was found to inhibit progesterone-induced meiotic maturation of frog oocytes by preventing the phosphorylation and activation of mitogen-activated protein kinase (MAPK). Similarly, lethal toxin prevented the activation of MAPK in serum stimulated, ras-transformed NIH3T3 cells. In vitro analyses using recombinant proteins indicated that lethal factor proteolytically modified the NH2-terminus of both MAPKK1 and 2, rendering them inactive and hence incapable of activating MAPK. The consequences of this inactivation upon meiosis and transformed cells are also discussed. JF - Journal of applied microbiology AU - Duesbery, N S AU - Vande Woude, G F AD - ABL-Basic Research Program, NCI-FCRDC, Frederick, MD 21702, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 289 EP - 293 VL - 87 IS - 2 SN - 1364-5072, 1364-5072 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Antigens, Bacterial KW - Bacterial Toxins KW - Enzyme Inhibitors KW - Flavonoids KW - anthrax toxin KW - Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase Kinases KW - EC 2.7.12.2 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Phosphorylation KW - Meiosis -- drug effects KW - Mitogen-Activated Protein Kinases -- metabolism KW - Ranidae KW - Enzyme Activation -- drug effects KW - Mitogen-Activated Protein Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- pharmacology KW - Mice KW - Flavonoids -- pharmacology KW - Signal Transduction -- drug effects KW - Mitogen-Activated Protein Kinase Kinases -- antagonists & inhibitors KW - Anthrax -- pathology KW - Bacterial Toxins -- toxicity KW - Anthrax -- microbiology KW - Anthrax -- metabolism KW - Bacillus anthracis KW - Mitogen-Activated Protein Kinase Kinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70025957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+microbiology&rft.atitle=Anthrax+lethal+factor+causes+proteolytic+inactivation+of+mitogen-activated+protein+kinase+kinase.&rft.au=Duesbery%2C+N+S%3BVande+Woude%2C+G+F&rft.aulast=Duesbery&rft.aufirst=N&rft.date=1999-08-01&rft.volume=87&rft.issue=2&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+microbiology&rft.issn=13645072&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-04 N1 - Date created - 1999-11-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Maternal and developmental toxicity evaluation of melatonin administered orally to pregnant Sprague-Dawley rats. AN - 70016730; 10478864 AB - Melatonin (MEL) is a widely used, over-the-counter sleep aid, and it has putative contraceptive, antioxidant, antiaging, and anticancer effects. The developmental toxicity potential for repeated oral doses of MEL had not previously been evaluated. In the present studies, time-mated, Sprague-Dawley-derived (CD) rats were administered MEL or vehicle by gavage on gestation days (gd) 6-19. MEL-treated groups received 1-, 10-, 100-, 150-, or 200-mg/kg body weight/day in the screening study (15 rats/group), and 50, 100, or 200 mg/kg/day in the definitive study (25 rats/group). In both studies, maternal food/water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20, both studies), maternal liver and gravid uterine weights, number of ovarian corpora lutea, conceptus survival, fetal sex, and fetal body weight were evaluated. Fetal morphological examination included external structures (both studies) as well as visceral and skeletal structures (definitive study). In the screening study, maternal serum levels of 17beta-estradiol, progesterone, prolactin, and luteinizing hormone were determined by radioimmunoassay, and mammary tissue was fixed, stained, and evaluated for percent glandular area within the fat pad. No maternal morbidity/mortality was found in either study. In the screening study, aversion to treatment (> or =100 mg/kg/day) and reduced maternal weight gain (> or =150 mg/kg/day) were noted, but reproductive/endocrine parameters and fetal development were not affected. In the definitive study, aversion to treatment was noted at > or =50 mg/kg/day, and mild sedation, reduced maternal food intake, and reduced body weight gain were found during initial treatment with 200 mg/kg/day. MEL had no effect on prenatal survival, fetal body weight, or incidences of fetal malformations/variations. Thus, in the definitive study, the maternal toxicity NOAEL and LOAEL were 100 and 200 mg/kg/day, respectively, and the developmental toxicity NOAEL was > or =200 mg/kg/day. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Jahnke, G AU - Marr, M AU - Myers, C AU - Wilson, R AU - Travlos, G AU - Price, C AD - Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Jahnke@NIEHS.NIH.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 271 EP - 279 VL - 50 IS - 2 SN - 1096-6080, 1096-6080 KW - Antioxidants KW - 0 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Rats KW - Eating -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Aversive Therapy -- methods KW - Survival Rate KW - Drinking -- drug effects KW - Body Weight -- drug effects KW - Radioimmunoassay KW - Male KW - Female KW - Pregnancy KW - Fetus -- drug effects KW - Maternal-Fetal Exchange -- drug effects KW - Reproduction -- drug effects KW - Melatonin -- toxicity KW - Antioxidants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70016730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Maternal+and+developmental+toxicity+evaluation+of+melatonin+administered+orally+to+pregnant+Sprague-Dawley+rats.&rft.au=Jahnke%2C+G%3BMarr%2C+M%3BMyers%2C+C%3BWilson%2C+R%3BTravlos%2C+G%3BPrice%2C+C&rft.aulast=Jahnke&rft.aufirst=G&rft.date=1999-08-01&rft.volume=50&rft.issue=2&rft.spage=271&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-28 N1 - Date created - 1999-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Association of low-voltage alpha EEG with a subtype of alcohol use disorders. AN - 70010339; 10470973 AB - Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. We evaluated these findings using an independent, similarly established, dataset of 120 subjects. We also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 times) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low-amplitude alpha activity that was associated with alcohol use disorders. The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders. JF - Alcoholism, clinical and experimental research AU - Enoch, M A AU - White, K V AU - Harris, C R AU - Robin, R W AU - Ross, J AU - Rohrbaugh, J W AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-8110, USA. maenoch@dicbr.niaaa.nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1312 EP - 1319 VL - 23 IS - 8 SN - 0145-6008, 0145-6008 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Phenotype KW - Aged, 80 and over KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Adolescent KW - Male KW - Female KW - Anxiety Disorders -- genetics KW - Alcoholism -- genetics KW - Alcoholism -- complications KW - Anxiety Disorders -- complications KW - Alpha Rhythm UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70010339?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Association+of+low-voltage+alpha+EEG+with+a+subtype+of+alcohol+use+disorders.&rft.au=Enoch%2C+M+A%3BWhite%2C+K+V%3BHarris%2C+C+R%3BRobin%2C+R+W%3BRoss%2C+J%3BRohrbaugh%2C+J+W%3BGoldman%2C+D&rft.aulast=Enoch&rft.aufirst=M&rft.date=1999-08-01&rft.volume=23&rft.issue=8&rft.spage=1312&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-26 N1 - Date created - 1999-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic tolerance and sensitization to alcohol in sons of alcoholics: II. Replication and reanalysis. AN - 70007670; 10472511 AB - Data from D. B. Newlin and J. B. Thomson (1991) were reanalyzed, and data from an independent replication study were analyzed, relative to tonic (baseline) and phasic (response to alcohol challenge) aspects of drinking alcohol administered at the same dose on several occasions. Among the high-risk men (sons of alcoholic fathers), linear trends across days for resting (predrinking) baselines were opposite to alcohol-evoked changes for finger pulse amplitude, finger temperature, and skin conductance in Study 1 and for pulse transit time and body sway (static ataxia) in Study 2. In contrast, the structure of the low-risk men's (sons of nonalcoholic parents) data was precisely the opposite. Results are discussed in terms of sensitization as a potential mechanism that relates vulnerability to final manifestation of addictive behavior. JF - Experimental and clinical psychopharmacology AU - Newlin, D B AU - Thomson, J B AD - Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. dnewlin@irp.nida.nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 234 EP - 243 VL - 7 IS - 3 SN - 1064-1297, 1064-1297 KW - Central Nervous System Depressants KW - 0 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Humans KW - Regional Blood Flow -- drug effects KW - Motor Activity -- physiology KW - Postural Balance -- drug effects KW - Drug Tolerance KW - Heart Rate -- drug effects KW - Risk Factors KW - Adult KW - Heart Rate -- physiology KW - Galvanic Skin Response -- drug effects KW - Motor Activity -- drug effects KW - Regional Blood Flow -- physiology KW - Female KW - Galvanic Skin Response -- physiology KW - Male KW - Central Nervous System Depressants -- pharmacology KW - Ethanol -- pharmacology KW - Alcohol Drinking -- psychology KW - Alcohol Drinking -- physiopathology KW - Alcoholism -- physiopathology KW - Alcohol Drinking -- genetics KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70007670?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+and+clinical+psychopharmacology&rft.atitle=Chronic+tolerance+and+sensitization+to+alcohol+in+sons+of+alcoholics%3A+II.+Replication+and+reanalysis.&rft.au=Newlin%2C+D+B%3BThomson%2C+J+B&rft.aulast=Newlin&rft.aufirst=D&rft.date=1999-08-01&rft.volume=7&rft.issue=3&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Experimental+and+clinical+psychopharmacology&rft.issn=10641297&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Flavone acetic acid induces a G2/M cell cycle arrest in mammary carcinoma cells. AN - 70007069; 10471038 AB - Flavone acetic acid (FAA) is a synthetic flavonoid that demonstrated extraordinary anti-tumour properties in murine models but was not effective in clinical trials. In an effort to better understand the molecular mechanisms by which FAA asserts its tumouricidal activities, we have examined the effect of FAA on the cell cycle. We observed FAA-mediated G2/M cell cycle arrest in mammary carcinoma cells at a concentration previously demonstrated to have anti-tumour effects in rodent models. The cell cycle arrest was accompanied by an increase in the P34cdc2 (cdc2) cyclin-dependent kinase activity. Morphological cytogenetic analysis demonstrated a colcemid-like effect of FAA on cytokinesis by causing accumulation of condensed C-metaphases of a sustained mitotic block. The cell cycle effect was blocked by the antioxidants ADPC and ascorbate, the superoxide scavenger Tiron, and the sphingosine kinase inhibitor L-cycloserine, but not by inhibitors of nitric oxide synthase. Based on these data, we propose that FAA may induce cell cycle arrest by stimulating the activity of acidic sphingomyelinase leading to the generation of reactive oxygen species. JF - British journal of cancer AU - Panaro, N J AU - Popescu, N C AU - Harris, S R AU - Thorgeirsson, U P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1905 EP - 1911 VL - 80 IS - 12 SN - 0007-0920, 0007-0920 KW - Antineoplastic Agents KW - 0 KW - Flavonoids KW - RNA, Neoplasm KW - flavone acetic acid KW - 87626-55-9 KW - Cycloserine KW - 95IK5KI84Z KW - CDC2 Protein Kinase KW - EC 2.7.11.22 KW - Index Medicus KW - Rats KW - Animals KW - G2 Phase -- drug effects KW - Tumor Cells, Cultured KW - Mitotic Index -- drug effects KW - Metaphase -- drug effects KW - CDC2 Protein Kinase -- metabolism KW - Mitosis -- drug effects KW - Mammary Neoplasms, Experimental KW - RNA, Neoplasm -- analysis KW - Cycloserine -- pharmacology KW - Female KW - Flow Cytometry -- methods KW - Flavonoids -- antagonists & inhibitors KW - Antineoplastic Agents -- toxicity KW - Cell Cycle -- drug effects KW - Flavonoids -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70007069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Flavone+acetic+acid+induces+a+G2%2FM+cell+cycle+arrest+in+mammary+carcinoma+cells.&rft.au=Panaro%2C+N+J%3BPopescu%2C+N+C%3BHarris%2C+S+R%3BThorgeirsson%2C+U+P&rft.aulast=Panaro&rft.aufirst=N&rft.date=1999-08-01&rft.volume=80&rft.issue=12&rft.spage=1905&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-21 N1 - Date created - 1999-09-21 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Biol Cell. 1996 Nov;7(11):1749-58 [8930897] Cancer Res. 1996 Nov 1;56(21):4856-61 [8895733] Free Radic Biol Med. 1997;22(5):749-60 [9119242] Biochem Biophys Res Commun. 1997 Jun 27;235(3):509-14 [9207186] J Biol Chem. 1998 Jan 30;273(5):2591-600 [9446561] Nature. 1998 Mar 19;392(6673):300-3 [9521327] Eur J Cancer Clin Oncol. 1987 Jul;23(7):1047-50 [3665989] J Natl Cancer Inst. 1988 Apr 20;80(4):241-5 [3351960] Cell. 1988 Jul 1;54(1):17-26 [3289755] J Natl Cancer Inst. 1989 Feb 1;81(3):216-20 [2911084] J Natl Cancer Inst. 1989 Jul 5;81(13):1005-13 [2733044] Cancer Chemother Pharmacol. 1989;24(5):269-72 [2667786] FEBS Lett. 1990 Jan 15;260(1):10-3 [2298289] Br J Cancer. 1990 Aug;62(2):231-7 [2386739] Cancer Res. 1990 Nov 1;50(21):6966-70 [2170013] Proc Natl Acad Sci U S A. 1990 Dec;87(24):9553-7 [2263610] Cancer Res. 1991 Jan 1;51(1):77-81 [1988109] Eur J Cancer. 1990;26(10):1079-83 [2148884] Br J Cancer. 1991 Jun;63(6):889-92 [1712621] Int J Radiat Biol. 1991 Jul-Aug;60(1-2):379-84 [1677998] Cancer Res. 1991 Oct 1;51(19):5113-7 [1833048] Cancer Res. 1991 Dec 15;51(24):6596-602 [1742732] Biochem Pharmacol. 1992 Jun 9;43(11):2401-6 [1610403] Anticancer Res. 1992 Jul-Aug;12(4):1275-9 [1503421] Cancer Res. 1993 Mar 1;53(5):1128-35 [8439958] Cancer Res. 1993 Mar 15;53(6):1328-31 [8443813] Anticancer Drugs. 1993 Feb;4(1):3-17 [8457711] Eur J Cancer. 1993;29A(5):729-33 [8471332] Free Radic Biol Med. 1993 Oct;15(4):385-94 [8225020] Biochem Pharmacol. 1994 Feb 9;47(3):573-80 [8117326] Biochem Biophys Res Commun. 1994 Oct 28;204(2):578-84 [7980517] Cell Growth Differ. 1994 Oct;5(10):1041-50 [7848905] Trends Biochem Sci. 1995 Sep;20(9):342-4 [7482697] Anticancer Res. 1996 Jan-Feb;16(1):425-31 [8615648] Cancer Res. 1996 Jul 1;56(13):2973-8 [8674031] J Cell Sci. 1996 Sep;109 ( Pt 9):2407-15 [8886990] Carcinogenesis. 1996 Nov;17(11):2367-75 [8968050] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Animal models of rheumatoid arthritis. AN - 70002877; 10475714 JF - Molecular medicine today AU - Joe, B AU - Wilder, R L AD - Inflammatory Joint Diseases Section, Athritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 367 EP - 369 VL - 5 IS - 8 SN - 1357-4310, 1357-4310 KW - Adjuvants, Immunologic KW - 0 KW - Diamines KW - Extracellular Matrix Proteins KW - Glycoproteins KW - Matn1 protein, mouse KW - Matrilin Proteins KW - Proteoglycans KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Collagen KW - 9007-34-5 KW - avridine KW - P9J7O7YNSW KW - Index Medicus KW - Rats KW - Animals KW - Disease Models, Animal KW - Mice KW - Arthritis, Rheumatoid -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70002877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+medicine+today&rft.atitle=Animal+models+of+rheumatoid+arthritis.&rft.au=Joe%2C+B%3BWilder%2C+R+L&rft.aulast=Joe&rft.aufirst=B&rft.date=1999-08-01&rft.volume=5&rft.issue=8&rft.spage=367&rft.isbn=&rft.btitle=&rft.title=Molecular+medicine+today&rft.issn=13574310&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-02 N1 - Date created - 1999-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amphotericin B lipid complex in pediatric patients with invasive fungal infections. AN - 69995932; 10462340 AB - Lipid formulations of amphotericin B have been recently introduced for treatment of invasive fungal infections. However, little is known about their role in pediatric populations. We studied the safety and antifungal efficacy of amphotericin B lipid complex (ABLC, Abelcet) in 111 treatment episodes in pediatric patients through an open label, emergency use multicenter study. Patients with invasive fungal infections were enrolled if they had mycoses refractory to conventional antifungal therapy, if they were intolerant of previous systemic antifungal agents or concomitant nephrotoxic drugs or if they had preexisting renal disease. All 111 treatment episodes were evaluable for safety and 54 were evaluable for efficacy. The mean serum creatinine for the study population did not significantly change between baseline (1.23 +/- 0.11 mg/dl) and cessation of ABLC therapy (1.32 +/- 0.12 mg/dl) during 6 weeks. There were no significant differences observed between initial and end-of-therapy levels of serum potassium, magnesium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and hemoglobin. However, there was an increase in mean total bilirubin (3.66 +/- 0.73 to 5.31 +/- 1.09 mg/dl) at the end of therapy (P = 0.054). Among 54 cases fulfilling criteria for evaluation of antifungal efficacy, a complete or partial therapeutic response was obtained in 38 patients (70%) after ABLC therapy. Complete or partial therapeutic response was documented in 56% of cases with aspergillosis (n = 25) and in 81% (n = 27) with candidiasis. Among premature infants (n = 8) and allogeneic marrow recipients (n = 14), response rates were 88 and 57%, respectively. Response was similar in those patients enrolled because of intolerance to previous antifungal therapy or because of progressive infection. These data support the use of ABLC for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy. JF - The Pediatric infectious disease journal AU - Walsh, T J AU - Seibel, N L AU - Arndt, C AU - Harris, R E AU - Dinubile, M J AU - Reboli, A AU - Hiemenz, J AU - Chanock, S J AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 702 EP - 708 VL - 18 IS - 8 SN - 0891-3668, 0891-3668 KW - Antifungal Agents KW - 0 KW - Drug Combinations KW - Phosphatidylcholines KW - Phosphatidylglycerols KW - liposomal amphotericin B KW - Amphotericin B KW - 7XU7A7DROE KW - Creatinine KW - AYI8EX34EU KW - Index Medicus KW - Humans KW - Aspergillosis -- drug therapy KW - Infant, Newborn KW - Child KW - Creatinine -- blood KW - Child, Preschool KW - Zygomycosis -- drug therapy KW - Infant KW - Candidiasis -- drug therapy KW - Adolescent KW - Female KW - Male KW - Antifungal Agents -- adverse effects KW - Amphotericin B -- administration & dosage KW - Phosphatidylglycerols -- adverse effects KW - Antifungal Agents -- therapeutic use KW - Phosphatidylcholines -- adverse effects KW - Phosphatidylcholines -- therapeutic use KW - Amphotericin B -- adverse effects KW - Phosphatidylglycerols -- therapeutic use KW - Antifungal Agents -- administration & dosage KW - Mycoses -- drug therapy KW - Phosphatidylcholines -- administration & dosage KW - Amphotericin B -- therapeutic use KW - Phosphatidylglycerols -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69995932?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Pediatric+infectious+disease+journal&rft.atitle=Amphotericin+B+lipid+complex+in+pediatric+patients+with+invasive+fungal+infections.&rft.au=Walsh%2C+T+J%3BSeibel%2C+N+L%3BArndt%2C+C%3BHarris%2C+R+E%3BDinubile%2C+M+J%3BReboli%2C+A%3BHiemenz%2C+J%3BChanock%2C+S+J&rft.aulast=Walsh&rft.aufirst=T&rft.date=1999-08-01&rft.volume=18&rft.issue=8&rft.spage=702&rft.isbn=&rft.btitle=&rft.title=The+Pediatric+infectious+disease+journal&rft.issn=08913668&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-26 N1 - Date created - 1999-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH. AN - 69968390; 10452615 AB - The monomer-dimer equilibrium for the human immunodeficiency virus type 1 (HIV-1) protease has been investigated under physiological conditions. Dimer dissociation at pH 7.0 was correlated with a loss in beta-sheet structure and a lower degree of ANS binding. An autolysis-resistant mutant, Q7K/L33I/L63I, was used to facilitate sedimentation equilibrium studies at neutral pH where the wild-type enzyme is typically unstable in the absence of bound inhibitor. The dimer dissociation constant (KD) of the triple mutant was 5.8 microM at pH 7.0 and was below the limit of measurement (approximately 100 nM) at pH 4.5. Similar studies using the catalytically inactive D25N mutant yielded a KD value of 1.0 microM at pH 7.0. These values differ significantly from a previously reported value of 23 nM obtained indirectly from inhibitor binding measurements (Darke et al., 1994). We show that the discrepancy may result from the thermodynamic linkage between the monomer-dimer and inhibitor binding equilibria. Under conditions where a significant degree of monomer is present, both substrates and competitive inhibitors will shift the equilibrium toward the dimer, resulting in apparent increases in dimer stability and decreases in ligand binding affinity. Sedimentation equilibrium studies were also carried out on several drug-resistant HIV-1 protease mutants: V82F, V82F/I84V, V82T/I84V, and L90M. All four mutants exhibited reduced dimer stability relative to the autolysis-resistant mutant at pH 7.0. Our results indicate that reductions in drug affinity may be due to the combined effects of mutations on both dimer stability and inhibitor binding. JF - Protein science : a publication of the Protein Society AU - Xie, D AU - Gulnik, S AU - Gustchina, E AU - Yu, B AU - Shao, W AU - Qoronfleh, W AU - Nathan, A AU - Erickson, J W AD - Structural Biochemistry Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA. xie@ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1702 EP - 1707 VL - 8 IS - 8 SN - 0961-8368, 0961-8368 KW - HIV Protease KW - EC 3.4.23.- KW - Index Medicus KW - AIDS/HIV KW - Mutagenesis, Site-Directed KW - Spectrometry, Fluorescence KW - Hydrogen-Ion Concentration KW - Enzyme Stability KW - Dimerization KW - Circular Dichroism KW - Ultracentrifugation KW - HIV Protease -- genetics KW - Drug Resistance, Microbial -- genetics KW - HIV Protease -- metabolism KW - HIV Protease -- chemistry KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69968390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Drug+resistance+mutations+can+effect+dimer+stability+of+HIV-1+protease+at+neutral+pH.&rft.au=Xie%2C+D%3BGulnik%2C+S%3BGustchina%2C+E%3BYu%2C+B%3BShao%2C+W%3BQoronfleh%2C+W%3BNathan%2C+A%3BErickson%2C+J+W&rft.aulast=Xie&rft.aufirst=D&rft.date=1999-08-01&rft.volume=8&rft.issue=8&rft.spage=1702&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1992 Oct 6;31(39):9491-501 [1390732] Biochemistry. 1992 Sep 1;31(34):7886-91 [1510976] Biochem Biophys Res Commun. 1993 Mar 31;191(3):998-1003 [8466539] Annu Rev Biochem. 1993;62:543-85 [8352596] Biochemistry. 1994 Jan 11;33(1):98-105 [8286367] Biochemistry. 1994 Aug 16;33(32):9405-13 [8068616] Methods Enzymol. 1994;241:104-27 [7854174] Methods Enzymol. 1994;241:254-78 [7854181] Biochemistry. 1995 Jul 25;34(29):9282-7 [7626598] Curr Top Microbiol Immunol. 1996;214:95-131 [8791726] Biochemistry. 1996 Oct 1;35(39):12957-62 [8841142] Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2243-8 [9122179] J Med Chem. 1997 Mar 28;40(7):1149-64 [9089336] J Virol. 1997 Aug;71(8):5774-81 [9223465] J Mol Biol. 1998 Oct 23;283(2):475-88 [9769219] J Mol Biol. 1965 Sep;13(2):482-95 [5867031] Prog Biophys Mol Biol. 1972;24:107-23 [4566650] J Biol Chem. 1975 Dec 25;250(24):9391-6 [1194291] Proc Natl Acad Sci U S A. 1988 Jul;85(13):4686-90 [3290901] J Biol Chem. 1989 Feb 5;264(4):2307-12 [2644259] Nature. 1990 Jan 4;343(6253):90-2 [1688646] Proteins. 1990;7(3):205-14 [2194218] Annu Rev Biophys Biophys Chem. 1990;19:189-215 [2194475] Proc Natl Acad Sci U S A. 1991 May 15;88(10):4528-32 [2034693] Methods Enzymol. 1991;204:125-39 [1943776] J Virol. 1992 Nov;66(11):6781-3 [1404618] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced risk of AIDS lymphoma in individuals heterozygous for the CCR5-delta32 mutation. AN - 69962346; 10446961 AB - Non-Hodgkin's lymphoma (NHL) has been increasing in frequency in the industrialized world, but the environmental and genetic factors that contribute to susceptibility are not known. B-cell lymphomas represent a major cause of morbidity and mortality in HIV-infected individuals. The identification of a deletion in the CCR5 chemokine receptor gene that alters the risk for infection and progression to AIDS led us to examine a potential role of this gene in AIDS lymphoma. A matched case-control analysis was performed using all eligible NHL cases in the Multicenter AIDS Cohort Study. Patients were matched for age, study center, time AIDS-free, and slope of the CD4+ T-cell decline. The CCR5-delta32 allele was found to be associated with a 3-fold lower risk of NHL among individuals after controlling for time of infection and progression toward AIDS. The CCR5 gene was not associated with a difference in risk for Kaposi's sarcoma, another common malignancy in AIDS patients, or opportunistic infections. Costimulation of normal phorbol 12-myristate 13-acetate-treated B cells with the CCR5 ligand RANTES induced a proliferative response, indicating that RANTES is a mitogen for B cells. Taken together, these findings suggest that the CCR5 gene plays a role in the risk of NHL in HIV-infected patients, perhaps through a mechanism involving a decreased response of B cells to the mitogenic activity of RANTES. JF - Cancer research AU - Dean, M AU - Jacobson, L P AU - McFarlane, G AU - Margolick, J B AU - Jenkins, F J AU - Howard, O M AU - Dong, H F AU - Goedert, J J AU - Buchbinder, S AU - Gomperts, E AU - Vlahov, D AU - Oppenheim, J J AU - O'Brien, S J AU - Carrington, M AD - Laboratories of Genomic Diversity, National Cancer Institute, Frederick, Maryland 21702-1201, USA. Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 3561 EP - 3564 VL - 59 IS - 15 SN - 0008-5472, 0008-5472 KW - Chemokine CCL5 KW - 0 KW - Receptors, CCR5 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Chemokine CCL5 -- physiology KW - B-Lymphocytes -- pathology KW - Gene Frequency KW - Humans KW - Sarcoma, Kaposi -- genetics KW - Sarcoma, Kaposi -- epidemiology KW - AIDS-Related Opportunistic Infections -- epidemiology KW - AIDS-Related Opportunistic Infections -- genetics KW - European Continental Ancestry Group -- genetics KW - HIV-1 KW - Risk KW - B-Lymphocytes -- drug effects KW - Adult KW - Cohort Studies KW - Case-Control Studies KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genetic Predisposition to Disease KW - Male KW - Sequence Deletion KW - Lymphoma, AIDS-Related -- epidemiology KW - Receptors, CCR5 -- genetics KW - Point Mutation KW - Lymphoma, AIDS-Related -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69962346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Reduced+risk+of+AIDS+lymphoma+in+individuals+heterozygous+for+the+CCR5-delta32+mutation.&rft.au=Dean%2C+M%3BJacobson%2C+L+P%3BMcFarlane%2C+G%3BMargolick%2C+J+B%3BJenkins%2C+F+J%3BHoward%2C+O+M%3BDong%2C+H+F%3BGoedert%2C+J+J%3BBuchbinder%2C+S%3BGomperts%2C+E%3BVlahov%2C+D%3BOppenheim%2C+J+J%3BO%27Brien%2C+S+J%3BCarrington%2C+M&rft.aulast=Dean&rft.aufirst=M&rft.date=1999-08-01&rft.volume=59&rft.issue=15&rft.spage=3561&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-07 N1 - Date created - 1999-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Elevated mutant frequencies in lymphoid tissues persist throughout plasmacytoma development in BALB/c.lambdaLIZ mice. AN - 69961788; 10446972 AB - Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, the mean mutant frequencies in the target gene, lacI, were found to be significantly increased in lymphoid tissues of congenic BALB/c.lambdaLIZ N5 mice in the terminal stage of a plasmacytoma induction experiment, 213-280 days after the first i.p. injection of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane). In plasmacytoma-bearing mice (n = 7), mutant frequencies in the spleens and mesenteric lymph nodes were elevated 2.46-fold and 5.35-fold, respectively, when compared with age-matched controls. In plasmacytoma-negative mice (n = 11), mutant frequencies were increased 2.30-fold (spleens) and 3.48-fold (mesenteric nodes). These results, interpreted in conjunction with our previous findings (K. Felix et al., Cancer Res., 58: 1616-1619, 1998) of approximately 3-fold elevations in pristane-induced splenic mutagenesis on day 42 postpristane, indicate that increased mutant levels in lymphoid tissues persist throughout plasmacytomagenesis in genetically susceptible BALB/c mice. JF - Cancer research AU - Felix, K AU - Kelliher, K A AU - Bornkamm, G W AU - Janz, S AD - Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. felixk@dc37a.nci.nih.gov Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 3621 EP - 3626 VL - 59 IS - 15 SN - 0008-5472, 0008-5472 KW - Bacterial Proteins KW - 0 KW - Carcinogens KW - DNA, Neoplasm KW - Escherichia coli Proteins KW - Lac Repressors KW - Repressor Proteins KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Spleen -- chemistry KW - Animals KW - Bacterial Proteins -- genetics KW - DNA Mutational Analysis KW - Disease Progression KW - Lymph Nodes -- pathology KW - Spleen -- pathology KW - Mice KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Repressor Proteins -- genetics KW - Mutagenesis KW - Mice, Inbred C57BL KW - Lymph Nodes -- chemistry KW - DNA, Neoplasm -- genetics KW - Spleen -- drug effects KW - Lymph Nodes -- drug effects KW - Female KW - Male KW - Terpenes -- toxicity KW - Peritoneal Neoplasms -- chemically induced KW - Lymphoid Tissue -- pathology KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Carcinogens -- toxicity KW - Peritoneal Neoplasms -- genetics KW - Peritoneal Neoplasms -- pathology KW - Lac Operon -- genetics KW - Lymphoid Tissue -- chemistry KW - Plasmacytoma -- genetics KW - Genes, Reporter -- genetics KW - DNA -- genetics KW - Lymphoid Tissue -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69961788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Elevated+mutant+frequencies+in+lymphoid+tissues+persist+throughout+plasmacytoma+development+in+BALB%2Fc.lambdaLIZ+mice.&rft.au=Felix%2C+K%3BKelliher%2C+K+A%3BBornkamm%2C+G+W%3BJanz%2C+S&rft.aulast=Felix&rft.aufirst=K&rft.date=1999-08-01&rft.volume=59&rft.issue=15&rft.spage=3621&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-07 N1 - Date created - 1999-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convection-enhanced selective excitotoxic ablation of the neurons of the globus pallidus internus for treatment of parkinsonism in nonhuman primates. AN - 69946411; 10433318 AB - Selective treatment of central nervous system (CNS) structures holds therapeutic promise for many neurological disorders, including Parkinson's disease (PD). The ability to inhibit or augment specific neuronal populations within the CNS reliably by using present therapeutic techniques is limited. To overcome this problem, the authors modeled and developed a method in which convection was used to deliver compounds to deep brain nuclei in a reproducible, homogeneous, and targeted manner. To determine the feasibility and clinical efficacy of convective drug delivery for treatment of a neurological disorder, the investigators selectively ablated globus pallidus internus (GPi) neurons with quinolinic acid (QA), an excitotoxin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model of primate parkinsonism. After the parameters of convective distribution to the GPi were confirmed by infusion of biotinylated albumin into the GPi of a primate (Macaca mulatta), seven adult monkeys of this species were rendered either fully parkinsonian by intravenous injections of MPTP (five animals) or hemiparkinsonian by a right-sided intracarotid injection of this agent (two monkeys). Using convection-enhanced delivery to the GPi, animals were infused with either QA (three fully parkinsonian, two hemiparkinsonian) or saline (two fully parkinsonian). The three fully parkinsonian animals that underwent GPi lesioning with QA had substantial improvement of PD symptoms, manifested by a marked increase in activity (34 +/- 2.5%; mean +/- standard deviation) and dramatic improvement of parkinsonian clinical scores. In contrast, the control animals did not improve (activity monitor change = -1.5 +/- 0.5%). The two hemiparkinsonian animals that underwent QA lesioning of the GPi had dramatic recovery of extremity use. Histological examination revealed selective neural ablation of GPi neurons (mean loss 87%) with sparing of surrounding gray and white matter structures. No animal developed worsening signs of PD or neurological deficits after infusion. Convection-enhanced delivery of QA permits selective, region-specific (GPi), and safe lesioning of neuronal subpopulations, resulting in dramatic improvement in parkinsonian symptomatology. The properties of convection-enhanced delivery indicate that this method could be used for chemical neurosurgery for medically refractory PD and that it may be ideal for cell-specific therapeutic ablation or trophic treatment of other targeted structures associated with CNS disorders. JF - Journal of neurosurgery AU - Lonser, R R AU - Corthésy, M E AU - Morrison, P F AU - Gogate, N AU - Oldfield, E H AD - Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, and Bioengineering and Physical Science Program, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 294 EP - 302 VL - 91 IS - 2 SN - 0022-3085, 0022-3085 KW - Albumins KW - 0 KW - Antiparkinson Agents KW - Dopamine Agents KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Quinolinic Acid KW - F6F0HK1URN KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Feasibility Studies KW - Reproducibility of Results KW - Extracellular Space -- metabolism KW - Albumins -- pharmacokinetics KW - Disease Models, Animal KW - Motor Activity -- drug effects KW - Models, Chemical KW - Macaca mulatta KW - Quinolinic Acid -- administration & dosage KW - Globus Pallidus -- pathology KW - Drug Delivery Systems KW - Globus Pallidus -- metabolism KW - Antiparkinson Agents -- administration & dosage KW - Neurons -- drug effects KW - Globus Pallidus -- drug effects KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- pathology KW - Parkinson Disease -- drug therapy KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69946411?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Convection-enhanced+selective+excitotoxic+ablation+of+the+neurons+of+the+globus+pallidus+internus+for+treatment+of+parkinsonism+in+nonhuman+primates.&rft.au=Lonser%2C+R+R%3BCorth%C3%A9sy%2C+M+E%3BMorrison%2C+P+F%3BGogate%2C+N%3BOldfield%2C+E+H&rft.aulast=Lonser&rft.aufirst=R&rft.date=1999-08-01&rft.volume=91&rft.issue=2&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-16 N1 - Date created - 1999-08-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Neurosurg. 2000 Aug;93(2):364-6 [10930028] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue and site-specific methylation correlates with expression of the mouse lactoferrin gene. AN - 69944649; 10425446 AB - We have previously examined the regulatory region of the mouse lactoferrin gene and have identified sequences essential for basal and hormonally induced expression. In this study, we explore the relationship between the methylation state of the mouse lactoferrin gene promoter and its expression in selected mouse tissues. In a transient expression system, transcriptional activity was blocked after in vitro methylation of the regulatory region of the mouse lactoferrin gene. In addition, the in vivo methylation state of three promoter region sites was assessed using Southern blot analysis of DNA digested with methylation-insensitive and -sensitive restriction enzymes. The results showed that site -455, upstream of the mouse lactoferrin estrogen response module, was highly unmethylated in DNA from both hormone-treated and -untreated mouse lung, liver, and spleen tissues. Also, in both treated and untreated samples, the -54 site is uniquely highly unmethylated in liver DNA, while the -22 site is unmethylated in spleen DNA. Northern blot analysis showed lactoferrin expression in tissues that were unmethylated at a minimum of two sites. These results show that the alteration of the methylation status of the three sites are tissue-specific and are associated with constitutive expression of lactoferrin. JF - Journal of molecular endocrinology AU - Grant, D J AU - Shi, H AU - Teng, C T AD - Gene Regulation Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 45 EP - 55 VL - 23 IS - 1 SN - 0952-5041, 0952-5041 KW - Estrogens, Non-Steroidal KW - 0 KW - Recombinant Fusion Proteins KW - Diethylstilbestrol KW - 731DCA35BT KW - DNA KW - 9007-49-2 KW - DNA modification methylase HpaII KW - EC 2.1.1.- KW - DNA-Cytosine Methylases KW - Chloramphenicol O-Acetyltransferase KW - EC 2.3.1.28 KW - Deoxyribonuclease HpaII KW - EC 3.1.21.- KW - Lactoferrin KW - EC 3.4.21.- KW - Index Medicus KW - Gene Expression -- drug effects KW - Animals KW - Humans KW - Liver -- metabolism KW - Brain -- metabolism KW - Deoxyribonuclease HpaII -- metabolism KW - Uterus -- metabolism KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - DNA-Cytosine Methylases -- metabolism KW - Recombinant Fusion Proteins -- genetics KW - Promoter Regions, Genetic -- genetics KW - Kidney -- metabolism KW - Spleen -- metabolism KW - DNA -- metabolism KW - Mice KW - Lung -- metabolism KW - Chloramphenicol O-Acetyltransferase -- metabolism KW - DNA -- drug effects KW - Chloramphenicol O-Acetyltransferase -- genetics KW - Methylation -- drug effects KW - DNA -- genetics KW - Diethylstilbestrol -- pharmacology KW - Estrogens, Non-Steroidal -- pharmacology KW - Female KW - Lactoferrin -- genetics KW - Lactoferrin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69944649?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+endocrinology&rft.atitle=Tissue+and+site-specific+methylation+correlates+with+expression+of+the+mouse+lactoferrin+gene.&rft.au=Grant%2C+D+J%3BShi%2C+H%3BTeng%2C+C+T&rft.aulast=Grant&rft.aufirst=D&rft.date=1999-08-01&rft.volume=23&rft.issue=1&rft.spage=45&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+endocrinology&rft.issn=09525041&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adolescent reproductive events and subsequent breast cancer risk. AN - 69934986; 10432916 AB - This study investigated the relationship between reproductive events during adolescence and subsequent breast cancer risk. Logistic regression models used self-reported data from 862 case patients and 790 controls in the Carolina Breast Cancer Study. Miscarriage, induced abortion, and full-term pregnancy before 20 years of age were not associated with breast cancer. Among premenopausal women, breast-feeding before 20 years of age was inversely associated with disease. Oral contraceptive use before 18 years of age was positively associated with disease risk among African American women only. Pregnancy during adolescence does not appear to influence breast cancer risk, but breast-feeding may. A possible increased breast cancer risk among African American women who used oral contraceptives as adolescents warrants further study. JF - American journal of public health AU - Marcus, P M AU - Baird, D D AU - Millikan, R C AU - Moorman, P G AU - Qaqish, B AU - Newman, B AD - Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-7354, USA. pm145q@nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1244 EP - 1247 VL - 89 IS - 8 SN - 0090-0036, 0090-0036 KW - Contraceptives, Oral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Breast Feeding -- adverse effects KW - Odds Ratio KW - Logistic Models KW - Risk Factors KW - Humans KW - Adult KW - Case-Control Studies KW - Middle Aged KW - Adolescent KW - Female KW - Pregnancy KW - Reproductive History KW - Pregnancy in Adolescence KW - Breast Neoplasms -- prevention & control KW - Breast Neoplasms -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69934986?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Adolescent+reproductive+events+and+subsequent+breast+cancer+risk.&rft.au=Marcus%2C+P+M%3BBaird%2C+D+D%3BMillikan%2C+R+C%3BMoorman%2C+P+G%3BQaqish%2C+B%3BNewman%2C+B&rft.aulast=Marcus&rft.aufirst=P&rft.date=1999-08-01&rft.volume=89&rft.issue=8&rft.spage=1244&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Breast Cancer Res Treat. 1995 Jul;35(1):51-60 [7612904] J Natl Cancer Inst. 1994 Nov 2;86(21):1584-92 [7932822] JAMA. 1996 Jan 24-31;275(4):283-7 [8544267] Development. 1996 Jan;122(1):181-93 [8565829] Cell Growth Differ. 1996 Jan;7(1):13-20 [8788029] N Engl J Med. 1997 Jan 9;336(2):81-5 [8988884] Ann Epidemiol. 1999 Apr;9(3):188-95 [10192651] Breast Cancer Res Treat. 1982;2(1):5-73 [6216933] Br J Cancer. 1983 Jun;47(6):757-62 [6860545] Am J Epidemiol. 1988 May;127(5):981-9 [2578017] J Clin Epidemiol. 1989;42(10):963-73 [2681548] Biometrics. 1990 Dec;46(4):963-75 [2085641] Am J Epidemiol. 1991 Aug 15;134(4):421-32 [1877602] Am J Epidemiol. 1991 Nov 1;134(9):1003-8 [1951288] Epidemiol Rev. 1993;15(1):17-35 [8405201] Epidemiol Rev. 1993;15(1):256-63 [8405209] Epidemiol Rev. 1993;15(1):36-47 [8405211] N Engl J Med. 1994 Jan 13;330(2):81-7 [8259187] Cancer Causes Control. 1995 Jul;6(4):321-31 [7548719] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Depletion of systemic macrophages by liposome-encapsulated clodronate attenuates increases in brain quinolinic acid during CNS-localized and systemic immune activation. AN - 69931137; 10428075 AB - Quinolinic acid is a neurotoxic tryptophan metabolite produced locally during immune activation. The present study tested the hypothesis that macrophages are an important source. In normal gerbils, the macrophage toxin liposome-encapsulated clodronate depleted blood monocytes and decreased quinolinic acid levels in liver (85%), duodenum (33%), and spleen (51%) but not serum or brain. In a model of CNS inflammation (an intrastriatal injection of 5 microg of lipopolysaccharide), striatal quinolinic acid levels were markedly elevated on day 4 after lipopolysaccharide in conjunction with infiltration with macrophages (lectin stain). Liposome-encapsulated clodronate given 1 day before intrastriatal lipopolysaccharide markedly reduced parenchymal macrophage invasion in response to lipopolysaccharide infusion and attenuated the increases in brain quinolinic acid (by 60%). A systemic injection of lipopolysaccharide (450 microg/kg) increased blood (by 38-fold), lung (34-fold), liver (23-fold), spleen (8-fold), and striatum (25-fold) quinolinic acid concentrations after 1 day. Liposome-encapsulated clodronate given 4 days before systemic lipopolysaccharide significantly attenuated the increases in quinolinic acid levels in blood (by 80%), liver (87%), spleen (80%), and striatum (68%) but had no effect on the increases in quinolinic acid levels in lung. These results are consistent with the hypothesis that macrophages are an important local source of quinolinic acid in brain and systemic tissues during immune activation. JF - Journal of neurochemistry AU - Koennecke, L A AU - Zito, M A AU - Proescholdt, M G AU - van Rooijen, N AU - Heyes, M P AD - Laboratory of Neurotoxicology, National Institute of Mental Health, Bethesda, Maryland 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 770 EP - 779 VL - 73 IS - 2 SN - 0022-3042, 0022-3042 KW - Griffonia simplicifolia lectins KW - 0 KW - Lectins KW - Lipopolysaccharides KW - Liposomes KW - Plant Lectins KW - Clodronic Acid KW - 0813BZ6866 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Animals KW - Corpus Striatum -- cytology KW - Gerbillinae KW - Drug Compounding KW - Lipopolysaccharides -- pharmacology KW - Corpus Striatum -- metabolism KW - Cerebellum -- immunology KW - Neuroimmunomodulation -- drug effects KW - Cerebellum -- metabolism KW - Cerebellum -- cytology KW - Microglia -- cytology KW - Encephalitis -- chemically induced KW - Female KW - Corpus Striatum -- immunology KW - Macrophages -- cytology KW - Clodronic Acid -- pharmacology KW - Quinolinic Acid -- cerebrospinal fluid KW - Brain Chemistry -- immunology KW - Quinolinic Acid -- blood KW - Brain Chemistry -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69931137?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Depletion+of+systemic+macrophages+by+liposome-encapsulated+clodronate+attenuates+increases+in+brain+quinolinic+acid+during+CNS-localized+and+systemic+immune+activation.&rft.au=Koennecke%2C+L+A%3BZito%2C+M+A%3BProescholdt%2C+M+G%3Bvan+Rooijen%2C+N%3BHeyes%2C+M+P&rft.aulast=Koennecke&rft.aufirst=L&rft.date=1999-08-01&rft.volume=73&rft.issue=2&rft.spage=770&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-13 N1 - Date created - 1999-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hematopoietic cancer and peptic ulcer: a multicenter case-control study. AN - 69930031; 10426792 AB - Helicobacter pylori has been suggested as a cause of gastric carcinoma and gastric non-Hodgkin's lymphoma (NHL). In a previous cohort study, a relative risk of six for gastric NHL was reported among subjects who tested positive for anti-H.pylori antibodies. The association between peptic ulcer and NHL has been studied in a population-based case-control investigation on hemato-lymphopoietic malignancies in Italy, based on face-to-face interviews to 2671 cases and 1718 controls (refusal rates 10 and 19%, respectively). Subjects who reported a diagnosis of peptic ulcer had a relative risk of 5.6 [95% confidence interval (CI) 3.8-8.0] for gastric NHL, whereas the estimate for non-gastric NHL was 1.3 (1.0-1.6). The association with recent diagnosis of ulcer was stronger, but the odds ratio (OR) was as high as 2.1 (95% CI 1.1-4.2) after >/=20 years since such diagnosis. After exclusion of the last 2 years before the diagnosis of NHL, and of ulcers diagnosed before 1978 (when gastroscopy became common in Italy), the OR was still 5.3 (95% CI 3.0-9.2). We found a strong effect modification by educational level, with ORs for ulcer more elevated in higher social groups. Gender was an effect modifier (OR = 4.1 in males, 9.2 in females; P = 0.03 for heterogeneity). The association with other gastrointestinal pathologies was much lower and statistically not significant. Almost all gastric lymphomas were B-cell NHLs of intermediate grade according to the working formulation; the majority belonged to the mucosa-associated lymphoid tissue (MALT) type. The association with ulcer was much stronger among MALT lymphomas, but only for recent ulcer diagnoses (2-10 years). Our study shows an increased risk for gastric NHL, very similar to the estimate reported in a previous cohort study. The risk was higher among more educated subjects. JF - Carcinogenesis AU - Vineis, P AU - Crosignani, P AU - Sacerdote, C AU - Fontana, A AU - Masala, G AU - Miligi, L AU - Nanni, O AU - Ramazzotti, V AU - Rodella, S AU - Stagnaro, E AU - Tumino, R AU - Viganò, C AU - Vindigni, C AU - Costantini, A S AD - Unit of Cancer Epidemiology, Ospedale S. Giovanni and CPO-Piemonte, via Santena 7, I-10126 Torino, Unit of Epidemiology, National Cancer Institute, Milano, Italy. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1459 EP - 1463 VL - 20 IS - 8 SN - 0143-3334, 0143-3334 KW - Index Medicus KW - Risk KW - Odds Ratio KW - Educational Status KW - Sex Factors KW - Lymphoma, B-Cell, Marginal Zone -- microbiology KW - Lymphoma, B-Cell, Marginal Zone -- complications KW - Humans KW - Adult KW - Case-Control Studies KW - Aged KW - Middle Aged KW - Male KW - Female KW - Stomach Neoplasms -- microbiology KW - Stomach Neoplasms -- complications KW - Helicobacter pylori KW - Peptic Ulcer -- complications KW - Peptic Ulcer -- microbiology KW - Lymphoma, Non-Hodgkin -- complications KW - Helicobacter Infections -- complications KW - Lymphoma, Non-Hodgkin -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69930031?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Hematopoietic+cancer+and+peptic+ulcer%3A+a+multicenter+case-control+study.&rft.au=Vineis%2C+P%3BCrosignani%2C+P%3BSacerdote%2C+C%3BFontana%2C+A%3BMasala%2C+G%3BMiligi%2C+L%3BNanni%2C+O%3BRamazzotti%2C+V%3BRodella%2C+S%3BStagnaro%2C+E%3BTumino%2C+R%3BVigan%C3%B2%2C+C%3BVindigni%2C+C%3BCostantini%2C+A+S&rft.aulast=Vineis&rft.aufirst=P&rft.date=1999-08-01&rft.volume=20&rft.issue=8&rft.spage=1459&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kaposi's sarcoma and non-Hodgkin's lymphoma incidence trends in AIDS Clinical Trial Group study participants. AN - 69929904; 10430216 AB - Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. We therefore examined incidence trends of Kaposi's sarcoma and non-Hodgkin's lymphoma in patients with advanced HIV infection in nine AIDS Clinical Trial Group studies of antiviral therapies for HIV and cytomegalovirus infections. Among a total of 6587 patients enrolled between November 1987 and February 1997, there were 280 cases of Kaposi's sarcoma and 68 cases of non-Hodgkin's lymphoma. Incidence rates per 100 person-years of both malignancies declined in concert with decreases in mortality, but the decreases in Kaposi's sarcoma were more profound and consistent than the decreases in non-Hodgkin's lymphoma. These data suggest that current therapies have ameliorated the incidence of Kaposi's sarcoma, but may not have had an equal effect on non-Hodgkin's lymphoma. JF - Journal of acquired immune deficiency syndromes (1999) AU - Rabkin, C S AU - Testa, M A AU - Huang, J AU - Von Roenn, J H AD - Viral Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - S31 EP - S33 VL - 21 Suppl 1 SN - 1525-4135, 1525-4135 KW - Anti-HIV Agents KW - 0 KW - Antiviral Agents KW - Foscarnet KW - 364P9RVW4X KW - Indinavir KW - 5W6YA9PKKH KW - Ganciclovir KW - P9G3CKZ4P5 KW - Index Medicus KW - AIDS/HIV KW - Cytomegalovirus Retinitis -- drug therapy KW - Antiviral Agents -- therapeutic use KW - Ganciclovir -- therapeutic use KW - Humans KW - Retrospective Studies KW - Clinical Trials as Topic KW - Indinavir -- therapeutic use KW - Incidence KW - Foscarnet -- therapeutic use KW - Cytomegalovirus Retinitis -- complications KW - Lymphoma, AIDS-Related -- epidemiology KW - Lymphoma, AIDS-Related -- complications KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Lymphoma, Non-Hodgkin -- epidemiology KW - AIDS-Related Opportunistic Infections -- complications KW - HIV Infections -- complications KW - Lymphoma, Non-Hodgkin -- complications KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - Sarcoma, Kaposi -- epidemiology KW - Sarcoma, Kaposi -- complications KW - AIDS-Related Opportunistic Infections -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69929904?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.atitle=Kaposi%27s+sarcoma+and+non-Hodgkin%27s+lymphoma+incidence+trends+in+AIDS+Clinical+Trial+Group+study+participants.&rft.au=Rabkin%2C+C+S%3BTesta%2C+M+A%3BHuang%2C+J%3BVon+Roenn%2C+J+H&rft.aulast=Rabkin&rft.aufirst=C&rft.date=1999-08-01&rft.volume=21+Suppl+1&rft.issue=&rft.spage=S31&rft.isbn=&rft.btitle=&rft.title=Journal+of+acquired+immune+deficiency+syndromes+%281999%29&rft.issn=15254135&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-dependent antagonism between fluorouracil and paclitaxel in human breast cancer cells. AN - 69929329; 10424768 AB - The effects of 24-hr exposures to 5-fluorouracil (FUra) and paclitaxel in various sequences were studied in MCF-7 breast cancer cells to determine an optimal schedule for possible clinical use. In clonogenic assays, pre-exposure to FUra followed by paclitaxel resulted in marked antagonism, while sequential paclitaxel followed by FUra was optimal. Concurrent or pre-exposure to paclitaxel did not affect [3H]FUra metabolism, [3H]FUra-RNA incorporation, or the extent of FUra-mediated thymidylate synthase inhibition. Paclitaxel led to G2/M phase accumulation that persisted for up to 24 hr after drug exposure, while a 24-hr FUra exposure produced S-phase accumulation. FUra pre-exposure diminished paclitaxel-associated G2/M phase block, whereas subsequent exposure to FUra after paclitaxel did not. FUra exposure resulted in transient induction of p53 and p21, which returned to basal levels 24 hr after drug removal. p53 and p21 protein content also increased markedly during paclitaxel exposure, accompanied by phosphorylation of Bcl-2. Double-stranded DNA fragmentation (approximately 50 kb) was seen at 48 hr when cells were exposed to paclitaxel for an initial 24-hr period. Paclitaxel-associated DNA fragmentation was not prevented by concurrent or subsequent exposure to FUra. Thus, paclitaxel-mediated G2/M phase arrest appeared to be a crucial step in induction of DNA fragmentation. Since an initial 24-hr paclitaxel exposure did not interfere with subsequent FUra metabolism or thymidylate synthase inhibition, and delayed exposure to FUra did not impede either paclitaxel-mediated induction of mitotic blockade or DNA fragmentation, the sequence of paclitaxel followed by FUra is recommended for clinical trials. JF - Biochemical pharmacology AU - Grem, J L AU - Nguyen, D AU - Monahan, B P AU - Kao, V AU - Geoffroy, F J AD - Developmental Therapeutics Department, National Cancer Institute-Medicine Branch, National Naval Medical Center, Bethesda, MD 20889-5105, USA. jgrem@helix.nih.gov Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 477 EP - 486 VL - 58 IS - 3 SN - 0006-2952, 0006-2952 KW - Antimetabolites, Antineoplastic KW - 0 KW - Antineoplastic Agents, Phytogenic KW - CDKN1A protein, human KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA, Neoplasm KW - RNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Paclitaxel KW - P88XT4IS4D KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Breast Neoplasms -- drug therapy KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Cyclins -- biosynthesis KW - Drug Administration Schedule KW - Humans KW - Cell Division -- drug effects KW - DNA Damage -- drug effects KW - DNA, Neoplasm -- drug effects KW - Thymidylate Synthase -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Breast Neoplasms -- pathology KW - Drug Antagonism KW - Cell Cycle -- drug effects KW - RNA, Neoplasm -- metabolism KW - Fluorouracil -- antagonists & inhibitors KW - Paclitaxel -- antagonists & inhibitors KW - Antineoplastic Agents, Phytogenic -- pharmacology KW - Fluorouracil -- pharmacology KW - Paclitaxel -- pharmacology KW - Fluorouracil -- metabolism KW - Antineoplastic Agents, Phytogenic -- antagonists & inhibitors KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69929329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Sequence-dependent+antagonism+between+fluorouracil+and+paclitaxel+in+human+breast+cancer+cells.&rft.au=Grem%2C+J+L%3BNguyen%2C+D%3BMonahan%2C+B+P%3BKao%2C+V%3BGeoffroy%2C+F+J&rft.aulast=Grem&rft.aufirst=J&rft.date=1999-08-01&rft.volume=58&rft.issue=3&rft.spage=477&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-02 N1 - Date created - 1999-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Single-channel properties of BK-type calcium-activated potassium channels at a cholinergic presynaptic nerve terminal. AN - 69923289; 10420003 AB - 1. A high-conductance calcium-activated potassium channel (BK KCa) was characterized at a cholinergic presynaptic nerve terminal using the calyx synapse isolated from the chick ciliary ganglion. 2. The channel had a conductance of 210 pS in a 150 mM:150 mM K+ gradient, was highly selective for K+ over Na+, and was sensitive to block by external charybdotoxin or tetraethylammonium (TEA) and by internal Ba2+. At +60 mV it was activated by cytoplasmic calcium [Ca2+]i with a Kd of approximately 0.5 microM and a Hill coefficient of approximately 2.0. At 10 microM [Ca2+]i the channel was 50 % activated (V) at -8.0 mV with a voltage dependence (Boltzmann slope-factor) of 32.7 mV. The V values hyperpolarized with an increase in [Ca2+]i while the slope factors decreased. There were no overt differences in conductance or [Ca2+]i sensitivity between BK channels from the transmitter release face and the non-release face. 3. Open and closed times were fitted by two and three exponentials, respectively. The slow time constants were strongly affected by both [Ca2+]i and membrane potential changes. 4. In cell-attached patch recordings BK channel opening was enhanced by a prepulse permissive for calcium influx through the patch, suggesting that the channel can be activated by calcium ion influx through neighbouring calcium channels. 5. The properties of the presynaptic BK channel are well suited for rapid activation during the presynaptic depolarization and Ca2+ influx that are associated with transmitter release. This channel may play an important role in terminating release by rapid repolarization of the action potential. JF - The Journal of physiology AU - Sun, X P AU - Schlichter, L C AU - Stanley, E F AD - Synaptic Mechanisms Section, DIR, National Institute of Neurological Disorders and Stroke, Building 36, Room 5A25, National Institutes of Health, Bethesda, MD 20892-4156, USA. Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 639 EP - 651 VL - 518 ( Pt 3) SN - 0022-3751, 0022-3751 KW - Large-Conductance Calcium-Activated Potassium Channels KW - 0 KW - Potassium Channel Blockers KW - Potassium Channels KW - Potassium Channels, Calcium-Activated KW - Charybdotoxin KW - 115422-61-2 KW - Barium KW - 24GP945V5T KW - Tetraethylammonium KW - 66-40-0 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Tetraethylammonium -- pharmacology KW - Chick Embryo KW - Ganglia, Parasympathetic -- physiology KW - Membrane Potentials -- physiology KW - Algorithms KW - Charybdotoxin -- pharmacology KW - Ion Channel Gating -- drug effects KW - Calcium -- metabolism KW - Ion Channel Gating -- physiology KW - Patch-Clamp Techniques KW - Ganglia, Parasympathetic -- cytology KW - Kinetics KW - Barium -- pharmacology KW - Parasympathetic Nervous System -- physiology KW - Potassium Channels -- physiology KW - Presynaptic Terminals -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69923289?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+physiology&rft.atitle=Single-channel+properties+of+BK-type+calcium-activated+potassium+channels+at+a+cholinergic+presynaptic+nerve+terminal.&rft.au=Sun%2C+X+P%3BSchlichter%2C+L+C%3BStanley%2C+E+F&rft.aulast=Sun&rft.aufirst=X&rft.date=1999-08-01&rft.volume=518+%28+Pt+3%29&rft.issue=&rft.spage=639&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+physiology&rft.issn=00223751&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-04 N1 - Date created - 1999-10-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Pharmacol. 1988 Dec;95(4):1329-35 [2464391] FEBS Lett. 1986 Dec 1;209(1):117-21 [2433153] Am J Physiol. 1989 Sep;257(3 Pt 1):C470-80 [2782390] Brain Res. 1989 Dec 29;505(2):341-5 [2598055] J Physiol. 1989 Jul;414:201-22 [2575161] J Neurosci. 1990 Nov;10(11):3664-84 [1700083] J Neurosci. 1991 Apr;11(4):985-93 [2010819] Pflugers Arch. 1991 Mar;418(1-2):102-8 [2041716] Neuron. 1991 Oct;7(4):585-91 [1657055] Ann N Y Acad Sci. 1991;635:221-33 [1660236] J Neurosci. 1992 Jan;12(1):297-305 [1370323] J Gen Physiol. 1991 Dec;98(6):1161-79 [1723748] Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1325-9 [1371356] Pflugers Arch. 1992 Sep;421(6):558-65 [1331975] J Physiol. 1992 Nov;457:47-74 [1284313] Neuron. 1993 Apr;10(4):689-99 [8386529] J Physiol. 1992 Dec;458:41-67 [1302271] Hear Res. 1993 Apr;66(2):123-9 [7685332] J Neurophysiol. 1993 May;69(5):1433-42 [8389824] Science. 1993 Jul 9;261(5118):221-4 [7687074] Hear Res. 1993 May;67(1-2):13-9 [8340264] J Neurophysiol. 1993 Jul;70(1):284-98 [8395581] Neuron. 1993 Oct;11(4):645-55 [7691106] Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7578-82 [8052623] Neuron. 1994 Sep;13(3):671-81 [7917297] Neuron. 1994 Dec;13(6):1275-80 [7993621] J Neurosci. 1994 Dec;14(12):7713-25 [7996206] Neuron. 1995 Mar;14(3):645-50 [7695911] J Neurophysiol. 1995 Jan;73(1):178-89 [7714563] J Gen Physiol. 1995 Jan;105(1):49-72 [7730789] J Neurophysiol. 1995 Jun;73(6):2448-58 [7666151] J Neurosci. 1995 Sep;15(9):6110-23 [7545225] J Neurosci. 1996 Feb 1;16(3):955-63 [8558264] J Physiol. 1995 Dec 1;489 ( Pt 2):403-18 [8847636] Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2853-8 [9096310] J Neurosci. 1997 May 1;17(9):2990-3001 [9096135] Brain Res Mol Brain Res. 1997 Apr;45(1):33-40 [9105668] Neurosci Res. 1997 Mar;27(3):219-28 [9129180] J Gen Physiol. 1997 May;109(5):647-73 [9154910] Pflugers Arch. 1997 Aug;434(4):406-12 [9211806] Br J Pharmacol. 1997 Aug;121(8):1531-40 [9283685] Trends Neurosci. 1997 Sep;20(9):404-9 [9292969] Curr Opin Neurobiol. 1998 Jun;8(3):321-9 [9687354] Nature. 1998 Oct 29;395(6705):900-5 [9804423] Biophys J. 1988 Jun;53(6):919-34 [2456105] J Gen Physiol. 1981 Jun;77(6):629-46 [6267163] J Physiol. 1985 Apr;361:441-57 [2580982] J Pharmacol Exp Ther. 1985 Oct;235(1):241-7 [2413197] J Biol Chem. 1986 Nov 5;261(31):14607-13 [2429958] FEBS Lett. 1989 Jul 3;250(2):433-6 [2473920] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Autoimmunity to a pathogenic retinal antigen begins as a balanced cytokine response that polarizes towards type 1 in a disease-susceptible and towards type 2 in a disease-resistant genotype. AN - 69919665; 10421788 AB - Susceptible, but not resistant, strains of rodents immunized for induction of experimental autoimmune uveitis (EAU) with the uveitogenic protein interphotoreceptor retinoid-binding protein (IRBP) exhibit a type 1 response at the time of disease expression. Here we investigate the evolution of this response using the prototypic EAU-susceptible and EAU-resistant mouse strains, B10.A and BALB/c. Disease severity and IRBP-specific responses (proliferation, cytokines and antibody isotypes) were evaluated 7, 14 and 21 days after uveitogenic immunization. B10.A mice initially exhibited an IgG1-dominated antibody response, and their lymph node cells produced IL-4 and IL-5 in addition to IFN-gamma. On day 14 and 21, however, the IgG2a isotype became predominant, and the primed lymph node cells produced mainly IFN-gamma and IL-12. B10.A mice developed EAU before day 14. BALB/c mice initially produced IL-12 and IFN-gamma in addition to IL-5, IL-4 and IL-10. At later time points IL-12 and IFN-gamma production diminished, and IL-4, IL-5 and IL-10 increased. An IgG1-dominated antibody response was maintained throughout. BALB/c mice failed to develop EAU even at day 21. Thus, both susceptible and resistant genotypes initially mount a balanced, type 0-like cytokine response to a uveitogenic challenge, that subsequently polarizes towards type 1 in the susceptible strain and towards type 2 in the resistant strain. JF - International immunology AU - Sun, B AU - Sun, S H AU - Chan, C C AU - Wiggert, B AU - Caspi, R R AD - Laboratory of Immunology, and Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 1307 EP - 1312 VL - 11 IS - 8 SN - 0953-8178, 0953-8178 KW - Autoantibodies KW - 0 KW - Cytokines KW - Eye Proteins KW - Immunoglobulin Isotypes KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Activation KW - Animals KW - Disease Susceptibility KW - Cytokines -- biosynthesis KW - Autoantibodies -- blood KW - Autoimmunity KW - Mice KW - Mice, Inbred BALB C KW - Immunization KW - Female KW - Lymph Nodes -- immunology KW - Th1 Cells -- immunology KW - Retinol-Binding Proteins -- immunology KW - Uveitis -- physiopathology KW - Uveitis -- immunology KW - Th2 Cells -- immunology KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69919665?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunology&rft.atitle=Autoimmunity+to+a+pathogenic+retinal+antigen+begins+as+a+balanced+cytokine+response+that+polarizes+towards+type+1+in+a+disease-susceptible+and+towards+type+2+in+a+disease-resistant+genotype.&rft.au=Sun%2C+B%3BSun%2C+S+H%3BChan%2C+C+C%3BWiggert%2C+B%3BCaspi%2C+R+R&rft.aulast=Sun&rft.aufirst=B&rft.date=1999-08-01&rft.volume=11&rft.issue=8&rft.spage=1307&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-24 N1 - Date created - 1999-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lamivudine for chronic delta hepatitis. AN - 69914968; 10421666 AB - Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thiacytidine), an oral nucleoside analogue with marked effects against hepatitis B, as therapy in 5 patients with chronic hepatitis D. Five men, ages 38 to 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in serum, as well as persistent elevations in alanine aminotransferase (ALT) levels and liver histology showing severe chronic hepatitis with fibrosis or cirrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 months. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV-RNA levels serially during the year of treatment and for 6 months thereafter. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetectable even by polymerase chain reaction (PCR) in 4. However, all 5 patients remained HBsAg- and HDV-RNA-positive, and serum ALT levels and liver histology did not improve. All patients tolerated therapy well. When lamivudine was stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replication, but does not improve disease activity or lower HDV-RNA levels in patients with chronic delta hepatitis. JF - Hepatology (Baltimore, Md.) AU - Lau, D T AU - Doo, E AU - Park, Y AU - Kleiner, D E AU - Schmid, P AU - Kuhns, M C AU - Hoofnagle, J H AD - Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 546 EP - 549 VL - 30 IS - 2 SN - 0270-9139, 0270-9139 KW - Antiviral Agents KW - 0 KW - DNA, Viral KW - Hepatitis B Surface Antigens KW - RNA, Viral KW - Lamivudine KW - 2T8Q726O95 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Adult KW - DNA, Viral -- blood KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - RNA, Viral -- blood KW - Hepatitis B Surface Antigens -- blood KW - Antiviral Agents -- therapeutic use KW - Lamivudine -- adverse effects KW - Hepatitis D, Chronic -- virology KW - Lamivudine -- therapeutic use KW - Hepatitis D, Chronic -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69914968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Lamivudine+for+chronic+delta+hepatitis.&rft.au=Lau%2C+D+T%3BDoo%2C+E%3BPark%2C+Y%3BKleiner%2C+D+E%3BSchmid%2C+P%3BKuhns%2C+M+C%3BHoofnagle%2C+J+H&rft.aulast=Lau&rft.aufirst=D&rft.date=1999-08-01&rft.volume=30&rft.issue=2&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-12 N1 - Date created - 1999-08-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Hepatology. 1999 Aug;30(2):579-81 [10421673] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dopamine transporter: transmembrane phenylalanine mutations can selectively influence dopamine uptake and cocaine analog recognition. AN - 69911202; 10419565 AB - Cocaine blocks the normal role of the dopamine transporter (DAT) in terminating dopamine signaling through molecular interactions that are only partially understood. Cocaine analog structure-activity studies have suggested roles for both cationic and aromatic interactions among DAT, dopamine, and cocaine. We hypothesized that phenylalanine residues lying in putative DAT transmembrane (TM) domains were good candidates to contribute to aromatic and/or cationic interactions among DAT, dopamine, and cocaine. To test this idea, we characterized the influences of alanine substitution for each of 29 phenylalanine residues lying in or near a putative DAT TM domain. Cells express 22 mutants at near wild-type levels, manifest by DAT immunohistochemistry and binding of the radiolabeled cocaine analog [(3)H](-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT). Seven mutants fail to express at normal levels. Four mutations selectively reduce cocaine analog affinities. Alanine substitutions at Phe(76), Phe(98), Phe(390), and Phe(361) located in TM domains 1 and 2, the fourth extracellular loop near TM 4 and in TM 7, displayed normal affinities for dopamine but 3- to 8-fold reductions in affinities for CFT. One TM 3 mutation, F(155)A, selectively decreased dopamine affinity to less than 3% of wild-type levels while reducing CFT affinity less than 3-fold. In a current DAT structural model, each of the residues at which alanine substitution selectively reduces cocaine analog or dopamine affinities faces a central transporter cavity, whereas mutations that influence expression levels are more likely to lie at potential helix/helix interfaces. Specific, overlapping sets of phenylalanine residues contribute selectively to DAT recognition of dopamine and cocaine. JF - Molecular pharmacology AU - Lin, Z AU - Wang, W AU - Kopajtic, T AU - Revay, R S AU - Uhl, G R AD - Molecular Neurobiology Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 434 EP - 447 VL - 56 IS - 2 SN - 0026-895X, 0026-895X KW - Carrier Proteins KW - 0 KW - Dopamine Plasma Membrane Transport Proteins KW - Dopamine Uptake Inhibitors KW - Membrane Glycoproteins KW - Membrane Transport Proteins KW - Nerve Tissue Proteins KW - Nortropanes KW - Tritium KW - 10028-17-8 KW - 2-carbomethoxy-3-(4-fluorophenyl)nortropane KW - 127648-30-0 KW - Phenylalanine KW - 47E5O17Y3R KW - Cocaine KW - I5Y540LHVR KW - Alanine KW - OF5P57N2ZX KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - COS Cells KW - Models, Molecular KW - Nortropanes -- pharmacology KW - Biological Transport KW - Radioligand Assay KW - Structure-Activity Relationship KW - Mutagenesis KW - Alanine -- metabolism KW - Binding, Competitive KW - Alanine -- genetics KW - Immunohistochemistry KW - Amino Acid Substitution KW - Phenylalanine -- metabolism KW - Cocaine -- analogs & derivatives KW - Carrier Proteins -- metabolism KW - Carrier Proteins -- genetics KW - Dopamine -- metabolism KW - Phenylalanine -- genetics KW - Cocaine -- pharmacokinetics KW - Dopamine Uptake Inhibitors -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69911202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Dopamine+transporter%3A+transmembrane+phenylalanine+mutations+can+selectively+influence+dopamine+uptake+and+cocaine+analog+recognition.&rft.au=Lin%2C+Z%3BWang%2C+W%3BKopajtic%2C+T%3BRevay%2C+R+S%3BUhl%2C+G+R&rft.aulast=Lin&rft.aufirst=Z&rft.date=1999-08-01&rft.volume=56&rft.issue=2&rft.spage=434&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intrastriatal dopamine injection induces apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats. AN - 69910678; 10419543 AB - ABSTRACT More and more evidence suggests that increases in dopamine (DA) in striata may participate in neurodegenerative processes during acute ischemia, hypoxia, and excitotoxicity. With a rat model of intrastriatal DA injection, we studied the molecular events involved in DA toxicity. Intrastriatal injections of DA in amounts from 1 to 2 micromol result in apoptotic cell death, as indicated by terminal deoxynucleotidyl transferase labeling of DNA strand breaks and Klenow polymerase-catalyzed [(32)P]deoxycytidine triphosphate-labeled DNA laddering. Injections of DA produce a strong and prolonged activated protein 1 (AP-1) activity that contains c-fos, c-jun, and phosphorylated c-jun protein. DA injections also stimulate the activity of nuclear factor-kappaB (NF-kappaB), an oxidative stress-responsive transcription factor. Injection of curcumin at a dose that selectively inhibits AP-1 activation without affecting NF-kappaB activity attenuates DNA laddering induced by DA. Preinjection with SN50, a specific permeable recombinant NF-kappaB translocation inhibitor peptide, reduces DA-induced NF-kappaB activation and apoptosis. Moreover, preinjection of the antioxidant GSH significantly inhibits both DA-induced activation of transcription factors AP-1 and NF-kappaB and subsequent apoptosis. Thus, our data suggest that DA-oxidative stress-induced apoptosis in vivo is mediated by activation of transcription factors AP-1 and NF-kappaB. JF - Molecular pharmacology AU - Luo, Y AU - Hattori, A AU - Munoz, J AU - Qin, Z H AU - Roth, G S AD - Molecular Physiology and Genetics Section, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA. luoyq@helix.nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 254 EP - 264 VL - 56 IS - 2 SN - 0026-895X, 0026-895X KW - Antioxidants KW - 0 KW - NF-kappa B KW - Proto-Oncogene Proteins c-fos KW - Proto-Oncogene Proteins c-jun KW - Transcription Factor AP-1 KW - Glutathione KW - GAN16C9B8O KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Animals KW - Proto-Oncogene Proteins c-fos -- metabolism KW - Antioxidants -- pharmacology KW - Oxidative Stress KW - Rats, Wistar KW - Corpus Striatum KW - Proto-Oncogene Proteins c-jun -- metabolism KW - Glutathione -- pharmacology KW - Male KW - Dopamine -- pharmacology KW - Apoptosis KW - Transcription Factor AP-1 -- metabolism KW - NF-kappa B -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69910678?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Intrastriatal+dopamine+injection+induces+apoptosis+through+oxidation-involved+activation+of+transcription+factors+AP-1+and+NF-kappaB+in+rats.&rft.au=Luo%2C+Y%3BHattori%2C+A%3BMunoz%2C+J%3BQin%2C+Z+H%3BRoth%2C+G+S&rft.aulast=Luo&rft.aufirst=Y&rft.date=1999-08-01&rft.volume=56&rft.issue=2&rft.spage=254&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nup124p is a nuclear pore factor of Schizosaccharomyces pombe that is important for nuclear import and activity of retrotransposon Tf1. AN - 69904836; 10409764 AB - The long terminal repeat (LTR)-containing retrotransposon Tf1 propagates within the fission yeast Schizosaccharomyces pombe as the result of several mechanisms that are typical of both retrotransposons and retroviruses. To identify host factors that contribute to the transposition process, we mutagenized cultures of S. pombe and screened them for strains that were unable to support Tf1 transposition. One such strain contained a mutation in a gene we named nup124. The product of this gene contains 11 FXFG repeats and is a component of the nuclear pore complex. In addition to the reduced levels of Tf1 transposition, the nup124-1 allele caused a significant reduction in the nuclear localization of Tf1 Gag. Surprisingly, the mutation in nup124-1 did not cause any reduction in the growth rate, the nuclear localization of specific nuclear localization signal-containing proteins, or the cytoplasmic localization of poly(A) mRNA. A two-hybrid analysis and an in vitro precipitation assay both identified an interaction between Tf1 Gag and the N terminus of Nup124p. These results provide evidence for an unusual mechanism of nuclear import that relies on a direct interaction between a nuclear pore factor and Tf1 Gag. JF - Molecular and cellular biology AU - Balasundaram, D AU - Benedik, M J AU - Morphew, M AU - Dang, V D AU - Levin, H L AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 5768 EP - 5784 VL - 19 IS - 8 SN - 0270-7306, 0270-7306 KW - Fungal Proteins KW - 0 KW - Gene Products, gag KW - Macromolecular Substances KW - Nuclear Pore Complex Proteins KW - Nuclear Proteins KW - Retroelements KW - Schizosaccharomyces pombe Proteins KW - nup124 protein, S pombe KW - Index Medicus KW - AIDS/HIV KW - Microscopy, Fluorescence KW - Terminator Regions, Genetic KW - Alleles KW - Recombination, Genetic KW - Molecular Sequence Data KW - Biological Transport KW - Amino Acid Sequence KW - Terminal Repeat Sequences KW - Gene Products, gag -- metabolism KW - Mutagenesis KW - Schizosaccharomyces -- genetics KW - Fungal Proteins -- physiology KW - Nuclear Proteins -- genetics KW - Cell Nucleus -- metabolism KW - Schizosaccharomyces -- metabolism KW - Fungal Proteins -- genetics KW - Retroelements -- physiology KW - Nuclear Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69904836?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Nup124p+is+a+nuclear+pore+factor+of+Schizosaccharomyces+pombe+that+is+important+for+nuclear+import+and+activity+of+retrotransposon+Tf1.&rft.au=Balasundaram%2C+D%3BBenedik%2C+M+J%3BMorphew%2C+M%3BDang%2C+V+D%3BLevin%2C+H+L&rft.aulast=Balasundaram&rft.aufirst=D&rft.date=1999-08-01&rft.volume=19&rft.issue=8&rft.spage=5768&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1998 Feb;18(2):1105-14 [9448008] Mol Cell Biol. 1998 Feb;18(2):1115-24 [9448009] EMBO J. 1998 Feb 16;17(4):909-17 [9463369] J Cell Biol. 1995 May;129(4):939-55 [7744966] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] Mol Biol Cell. 1995 Apr;6(4):401-417 [7626806] Cell. 1983 Feb;32(2):371-7 [6337726] J Bacteriol. 1984 May;158(2):636-43 [6233260] J Cell Biol. 1984 Dec;99(6):2216-22 [6501421] J Cell Biol. 1990 Apr;110(4):883-94 [2324201] Cell. 1990 Jun 15;61(6):979-89 [2112428] Mol Cell Biol. 1990 Dec;10(12):6791-8 [2174117] Cell. 1991 Feb 8;64(3):615-23 [1991323] Methods Enzymol. 1991;194:795-823 [2005825] EMBO J. 1992 Mar;11(3):1145-53 [1312461] Cell. 1992 May 15;69(4):605-13 [1586943] J Cell Biol. 1992 Nov;119(4):705-23 [1385442] EMBO J. 1992 Dec;11(13):5051-61 [1464327] J Virol. 1993 Jan;67(1):119-30 [8380067] Gene. 1993 Jan 15;123(1):127-30 [8422996] Curr Genet. 1993 May-Jun;23(5-6):547-8 [8319314] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] Cell. 1995 Nov 17;83(4):569-76 [7585960] Cell. 1995 Dec 1;83(5):683-92 [8521485] Mol Cell Biol. 1996 Jan;16(1):338-46 [8524313] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):96-100 [8552683] Cell. 1998 Feb 6;92(3):327-36 [9476893] J Virol. 1998 Jul;72(7):6004-13 [9621063] Mol Biol Cell. 1998 Oct;9(10):2839-55 [9763447] J Cell Biol. 1998 Nov 16;143(4):875-85 [9817747] Gene. 1998 Nov 26;223(1-2):157-63 [9858717] Mol Cell Biol. 1999 Mar;19(3):2351-65 [10022921] J Cell Biol. 1993 Oct;123(2):275-84 [7691829] Nature. 1993 Oct 14;365(6447):666-9 [8105392] EMBO J. 1993 Dec;12(12):4885-95 [8223497] J Cell Biol. 1993 Nov;123(4):771-83 [8227139] Cell. 1993 Nov 19;75(4):791-803 [8242750] J Cell Biol. 1994 Jun;125(5):955-69 [8195299] Genetics. 1994 Mar;136(3):849-56 [8005439] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6992-6 [8041734] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7311-5 [8041786] Cell. 1994 Jul 29;78(2):275-89 [8044840] J Cell Biol. 1994 Oct;127(2):319-32 [7929578] EMBO J. 1995 Jan 3;14(1):76-87 [7828598] Mol Biol Cell. 1994 Nov;5(11):1185-98 [7865884] J Biol Chem. 1995 Mar 31;270(13):7411-9 [7706287] J Cell Biol. 1995 Dec;131(6 Pt 2):1677-97 [8557737] J Cell Biol. 1995 Dec;131(6 Pt 2):1699-713 [8557738] J Virol. 1996 Feb;70(2):1027-32 [8551560] Mol Cell Biol. 1996 Oct;16(10):5645-54 [8816477] Science. 1996 Oct 25;274(5287):624-7 [8849456] Gene. 1996 Oct 3;174(2):315-8 [8890754] J Virol. 1997 Jan;71(1):843-7 [8985428] Cell. 1997 Jan 10;88(1):5-8 [9019405] Genes Dev. 1997 Jan 15;11(2):270-85 [9009208] Nature. 1997 Apr 24;386(6627):779-87 [9126736] Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4451-6 [9114010] Curr Opin Cell Biol. 1997 Jun;9(3):401-11 [9159086] Curr Opin Cell Biol. 1997 Jun;9(3):412-9 [9159081] Mol Biol Cell. 1997 May;8(5):825-41 [9168469] Cell. 1997 May 30;89(5):715-25 [9182759] Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9825-30 [9275210] Mol Biol Cell. 1997 Aug;8(8):1461-79 [9285819] Yeast. 1997 Sep 30;13(12):1167-79 [9301023] EMBO J. 1997 Oct 1;16(19):5998-6007 [9312057] Genes Dev. 1998 Jan 15;12(2):175-85 [9436978] J Virol. 1998 Feb;72(2):1324-33 [9445033] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. AN - 69903957; 10411572 AB - Cytochrome P-450 (CYP) 2C19 is responsible for the metabolism of a number of therapeutic agents such as S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Genetic polymorphisms in this enzyme are responsible for the poor metabolizers (PM) of mephenytoin, which represent approximately 13-23% of Asians and 3-5% of Caucasians. Several polymorphisms contribute to this phenotype. We have isolated two new allelic variants that contribute to the PM phenotype in Caucasians. CYP2C19*7 contained a single T --> A nucleotide transversion in the invariant GT at the 5' donor splice site of intron 5. The second PM allele, CYP2C19*8, consisted of a T358C nucleotide transition in exon 3 that results in a Trp120Arg substitution. In a bacterial expression system, CYP2C198 protein exhibited a dramatic (approximately 90% and 70%) reduction in the metabolism of S-mephenytoin and tolbutamide, respectively, when compared with the wild-type CYP2C191B protein. Restriction fragment length polymerase chain reaction tests were developed to identify the new allelic variants. JF - The Journal of pharmacology and experimental therapeutics AU - Ibeanu, G C AU - Blaisdell, J AU - Ferguson, R J AU - Ghanayem, B I AU - Brosen, K AU - Benhamou, S AU - Bouchardy, C AU - Wilkinson, G R AU - Dayer, P AU - Goldstein, J A AD - National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 635 EP - 640 VL - 290 IS - 2 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Cytochrome P-450 Enzyme Inhibitors KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2C19 protein, human KW - Cytochrome P-450 CYP2C19 KW - Mephenytoin KW - R420KW629U KW - Index Medicus KW - Escherichia coli -- metabolism KW - Plasmids -- genetics KW - Exons KW - Humans KW - Escherichia coli -- genetics KW - Reverse Transcriptase Polymerase Chain Reaction KW - Phenotype KW - Mutagenesis, Site-Directed KW - France KW - Genotype KW - Polymerase Chain Reaction KW - Alleles KW - Polymorphism, Restriction Fragment Length KW - European Continental Ancestry Group KW - Introns KW - Lung -- enzymology KW - Mixed Function Oxygenases -- antagonists & inhibitors KW - Cytochrome P-450 Enzyme System -- genetics KW - Anticonvulsants -- metabolism KW - Mixed Function Oxygenases -- genetics KW - Mephenytoin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69903957?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=A+novel+transversion+in+the+intron+5+donor+splice+junction+of+CYP2C19+and+a+sequence+polymorphism+in+exon+3+contribute+to+the+poor+metabolizer+phenotype+for+the+anticonvulsant+drug+S-mephenytoin.&rft.au=Ibeanu%2C+G+C%3BBlaisdell%2C+J%3BFerguson%2C+R+J%3BGhanayem%2C+B+I%3BBrosen%2C+K%3BBenhamou%2C+S%3BBouchardy%2C+C%3BWilkinson%2C+G+R%3BDayer%2C+P%3BGoldstein%2C+J+A&rft.aulast=Ibeanu&rft.aufirst=G&rft.date=1999-08-01&rft.volume=290&rft.issue=2&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-18 N1 - Date created - 1999-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of DNA-dependent activities by the functional motifs of the high-mobility-group chromosomal proteins. AN - 69902324; 10409715 JF - Molecular and cellular biology AU - Bustin, M AD - Protein Section, Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. bustin@helix.nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 5237 EP - 5246 VL - 19 IS - 8 SN - 0270-7306, 0270-7306 KW - High Mobility Group Proteins KW - 0 KW - Nucleosomes KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Animals KW - Models, Molecular KW - Cell Nucleus -- metabolism KW - Humans KW - Nucleosomes -- metabolism KW - Protein Binding KW - Nucleic Acid Conformation KW - Structure-Activity Relationship KW - Binding Sites KW - High Mobility Group Proteins -- physiology KW - High Mobility Group Proteins -- chemistry KW - DNA -- metabolism KW - DNA -- chemistry KW - Protein Structure, Tertiary KW - High Mobility Group Proteins -- classification UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69902324?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Regulation+of+DNA-dependent+activities+by+the+functional+motifs+of+the+high-mobility-group+chromosomal+proteins.&rft.au=Bustin%2C+M&rft.aulast=Bustin&rft.aufirst=M&rft.date=1999-08-01&rft.volume=19&rft.issue=8&rft.spage=5237&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Cell Biol. 1995 Dec;15(12):6663-9 [8524231] Proc Natl Acad Sci U S A. 1976 Jun;73(6):1897-901 [1064861] Cell. 1979 Jan;16(1):181-9 [369705] Biochemistry. 1980 Sep 16;19(19):4466-71 [6157409] J Biol Chem. 1997 Nov 21;272(47):29904-10 [9368066] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13448-51 [9391045] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12845-50 [9371763] Biochem Soc Trans. 1997 Nov;25(4):S647 [9450075] J Mol Biol. 1997 Dec 12;274(4):454-65 [9417927] EMBO J. 1998 Feb 2;17(3):817-26 [9451006] J Virol. 1998 Mar;72(3):2125-31 [9499068] Genes Dev. 1998 Feb 15;12(4):462-72 [9472015] Nucleic Acids Res. 1998 Mar 15;26(6):1433-9 [9490789] Prog Cell Cycle Res. 1995;1:339-49 [9552376] EMBO J. 1998 Apr 1;17(7):2079-85 [9524129] J Biol Chem. 1998 Apr 17;273(16):9409-14 [9545265] J Biol Chem. 1998 Apr 17;273(16):9755-60 [9545312] Nature. 1998 Apr 30;392(6679):885-8 [9582068] Int J Biochem Cell Biol. 1998 Jul;30(7):761-6 [9722980] Bioessays. 1998 Jul;20(7):584-8 [9723008] Nucleic Acids Res. 1998 Oct 1;26(19):4413-21 [9742243] Cancer Res. 1998 Sep 15;58(18):4193-8 [9751634] Prog Nucleic Acid Res Mol Biol. 1998;61:379-422 [9752726] Annu Rev Biochem. 1998;67:545-79 [9759497] Mech Dev. 1998 Aug;76(1-2):57-66 [9767109] J Virol. 1998 Nov;72(11):8477-84 [9765384] Curr Opin Genet Dev. 1998 Oct;8(5):519-25 [9794825] Genes Dev. 1998 Nov 1;12(21):3343-56 [9808622] Mol Cell. 1998 Oct;2(4):457-67 [9809067] Genes Chromosomes Cancer. 1998 Dec;23(4):279-85 [9824199] Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14173-8 [9826673] EMBO J. 1998 Dec 1;17(23):6992-7001 [9843505] Nat Struct Biol. 1998 Dec;5(12):1025-8 [9846868] J Cell Biol. 1998 Dec 14;143(6):1427-36 [9852141] J Biol Chem. 1999 Jan 15;274(3):1525-32 [9880529] J Biol Chem. 1999 Jan 15;274(3):1628-34 [9880542] Mol Cell. 1998 Dec;2(6):829-39 [9885570] Biochemistry. 1999 Jan 12;38(2):589-95 [9888798] Mol Cell Biol. 1999 May;19(5):3466-73 [10207070] Nat Genet. 1999 Jul;22(3):276-80 [10391216] Exp Cell Res. 1985 Feb;156(2):295-310 [3881264] Cancer Res. 1985 Dec;45(12 Pt 1):6051-7 [2998592] J Biol Chem. 1994 Jun 24;269(25):17136-40 [8006019] Mol Cell Biol. 1994 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Sep 29;252(4):423-32 [7563062] Exp Cell Res. 1986 Mar;163(1):95-102 [3510889] EMBO J. 1987 Jul;6(7):1981-7 [2820715] J Biol Chem. 1990 May 25;265(15):8573-82 [1692833] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] Trends Biochem Sci. 1991 Mar;16(3):92-7 [1647556] Biochem J. 1991 Dec 1;280 ( Pt 2):491-7 [1747124] Proteins. 1991;11(4):281-96 [1758883] EMBO J. 1992 Dec;11(12):4497-506 [1425584] J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] EMBO J. 1993 Apr;12(4):1311-9 [8467791] Nucleic Acids Res. 1993 May 25;21(10):2493-501 [8506143] EMBO J. 1993 Aug;12(8):3237-47 [8344261] Nucleic Acids Res. 1993 Jul 25;21(15):3427-36 [8346022] EMBO J. 1993 Oct;12(10):3855-64 [8404854] EMBO J. 1994 Jan 15;13(2):416-24 [8313887] Cell. 1997 Feb 21;88(4):483-92 [9038339] Am J Pathol. 1997 Mar;150(3):911-8 [9060829] Genes Dev. 1997 Mar 1;11(5):629-39 [9119227] J Cell Biol. 1997 Apr 7;137(1):19-26 [9105033] Biochemistry. 1997 May 20;36(20):5992-9 [9166769] J Exp Med. 1997 Jun 2;185(11):2025-32 [9166431] EMBO J. 1997 May 15;16(10):2665-70 [9184213] Cancer Res. 1997 Jun 1;57(11):2276-80 [9187132] Mol Cell Biol. 1997 Jul;17(7):3649-62 [9199299] Mol Endocrinol. 1997 Jul;11(8):1009-19 [9212049] Nat Struct Biol. 1997 Aug;4(8):657-65 [9253416] Nucleic Acids Res. 1997 Sep 1;25(17):3523-31 [9254714] Nature. 1997 Sep 18;389(6648):251-60 [9305837] Mol Cell Biol. 1997 Oct;17(10):5843-55 [9315642] EMBO J. 1997 Oct 1;16(19):5943-54 [9312052] J Biol Chem. 1997 Oct 24;272(43):27476-83 [9341202] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Cell. 1994 Feb 25;76(4):609-22 [7510215] Nucleic Acids Res. 1994 Feb 11;22(3):285-92 [8127664] Bioessays. 1993 Aug;15(8):539-46 [8135767] Cell. 1994 Apr 8;77(1):5-8 [8156597] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3368-72 [8159753] Mol Cell Biol. 1994 May;14(5):3376-91 [8164686] EMBO J. 1994 Apr 15;13(8):1817-22 [8168480] Trends Genet. 1994 Mar;10(3):94-100 [8178371] J Biol Chem. 1997 Nov 7;272(45):28171-4 [9353261] Proc Natl Acad Sci U S A. 1998 May 12;95(10):5468-73 [9576905] Genomics. 1998 Apr 15;49(2):247-52 [9598312] Development. 1998 Jul;125(13):2521-32 [9609835] Cancer Genet Cytogenet. 1998 Jun;103(2):175-7 [9614921] Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7322-6 [9636147] Eur J Biochem. 1998 May 1;253(3):787-95 [9654080] Keio J Med. 1998 Jun;47(2):73-7 [9659816] Mol Cell Biol. 1998 Aug;18(8):4471-87 [9671457] J Biol Chem. 1998 Aug 7;273(32):20015-20 [9685339] Semin Cell Biol. 1995 Aug;6(4):247-55 [8562917] Cell. 1995 Dec 29;83(7):1091-100 [8548797] Cell. 1995 Dec 29;83(7):1101-11 [8548798] EMBO J. 1996 Feb 1;15(3):548-61 [8599938] Nucleic Acids Res. 1996 Mar 15;24(6):1047-51 [8604337] J Biol Chem. 1996 May 17;271(20):12009-16 [8662614] Oncogene. 1996 Feb 1;12(3):515-21 [8637707] Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6716-20 [8692884] Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 [8768072] Int J Dev Biol. 1996 Feb;40(1):177-87 [8735927] Genomics. 1996 Jan 15;31(2):207-14 [8824803] EMBO J. 1996 Sep 16;15(18):4981-91 [8890171] EMBO J. 1996 Nov 1;15(21):5897-906 [8918467] Eur J Biochem. 1997 Jan 15;243(1-2):151-9 [9030734] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mapping of the feline calicivirus proteinase responsible for autocatalytic processing of the nonstructural polyprotein and identification of a stable proteinase-polymerase precursor protein. AN - 69886812; 10400760 AB - Expression of the region of the feline calicivirus (FCV) ORF1 encoded by nucleotides 3233 to 4054 in an in vitro rabbit reticulocyte system resulted in synthesis of an active proteinase that specifically processes the viral nonstructural polyprotein. Site-directed mutagenesis of the cysteine (Cys1193) residue in the putative active site of the proteinase abolished autocatalytic cleavage as well as cleavage of the viral capsid precursor, suggesting that this "3C-like" proteinase plays an important role in proteolytic processing during viral replication. Expression of the region encoding the C-terminal portion of the FCV ORF1 (amino acids 942 to 1761) in bacteria allowed direct N-terminal sequence analysis of the virus-specific polypeptides produced in this system. The results of these analyses indicate that the proteinase cleaves at amino acid residues E960-A961, E1071-S1072, E1345-T1346, and E1419-G1420; however, the cleavage efficiency is varied. The E1071-S1072 cleavage site defined the N terminus of a 692-amino-acid protein that contains sequences with similarity to the picornavirus 3C proteinase and 3D polymerase domains. Immunoprecipitation of radiolabeled proteins from FCV-infected feline kidney cells with serum raised against the FCV ORF1 C-terminal region showed that this "3CD-like" proteinase-polymerase precursor protein is apparently stable and accumulates in cells during infection. JF - Journal of virology AU - Sosnovtseva, S A AU - Sosnovtsev, S V AU - Green, K Y AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 6626 EP - 6633 VL - 73 IS - 8 SN - 0022-538X, 0022-538X KW - Protein Precursors KW - 0 KW - Proteins KW - Viral Nonstructural Proteins KW - Viral Proteins KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - 3C proteases KW - EC 3.4.22.28 KW - Index Medicus KW - Animals KW - Humans KW - Open Reading Frames KW - Amino Acid Sequence KW - Chromosome Mapping KW - Proteins -- metabolism KW - Binding Sites KW - Mutagenesis KW - Sequence Analysis KW - Cats KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Cell Line KW - Catalysis KW - Viral Proteins -- genetics KW - Calicivirus, Feline -- enzymology KW - Protein Precursors -- metabolism KW - DNA-Directed RNA Polymerases -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Calicivirus, Feline -- genetics KW - Protein Processing, Post-Translational KW - Cysteine Endopeptidases -- chemistry KW - Viral Proteins -- metabolism KW - Viral Nonstructural Proteins -- metabolism KW - Cysteine Endopeptidases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69886812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Mapping+of+the+feline+calicivirus+proteinase+responsible+for+autocatalytic+processing+of+the+nonstructural+polyprotein+and+identification+of+a+stable+proteinase-polymerase+precursor+protein.&rft.au=Sosnovtseva%2C+S+A%3BSosnovtsev%2C+S+V%3BGreen%2C+K+Y&rft.aulast=Sosnovtseva&rft.aufirst=S&rft.date=1999-08-01&rft.volume=73&rft.issue=8&rft.spage=6626&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Curr Top Microbiol Immunol. 1990;161:49-87 [2169385] Arch Virol. 1989;108(1-2):69-79 [2596975] J Biol Chem. 1991 Mar 25;266(9):5412-6 [1848550] Virus Res. 1990 Nov;17(3):145-60 [2077782] Virology. 1991 Oct;184(2):664-76 [1840711] Virology. 1991 Oct;184(2):677-86 [1887589] J Gen Virol. 1991 Sep;72 ( Pt 9):2197-206 [1895057] Arch Virol. 1992;122(3-4):223-35 [1731695] J Virol. 1992 Dec;66(12):7481-9 [1331532] Virology. 1993 Jul;195(1):51-61 [8391187] EMBO J. 1993 Sep;12(9):3587-98 [8253083] J Biol Chem. 1994 Feb 4;269(5):3212-8 [8106356] Nature. 1994 May 5;369(6475):72-6 [8164744] Cell. 1994 Jun 3;77(5):761-71 [7515772] J Virol. 1994 Oct;68(10):6487-95 [8083986] Virology. 1995 Jul 10;210(2):383-90 [7618275] J Virol. 1995 Nov;69(11):7159-68 [7474137] J Virol. 1996 Feb;70(2):1261-5 [8551592] J Gen Virol. 1996 Jan;77 ( Pt 1):123-7 [8558120] J Virol. 1996 Apr;70(4):2605-10 [8642693] J Virol. 1996 Sep;70(9):5954-61 [8709217] J Virol. 1996 Nov;70(11):7974-83 [8892921] Protein Sci. 1996 Nov;5(11):2203-16 [8931139] J Biol Chem. 1997 Mar 21;272(12):7883-91 [9065455] J Gen Virol. 1997 May;78 ( Pt 5):1033-40 [9152420] J Virol. 1998 Apr;72(4):3051-9 [9525628] Nature. 1998 May 21;393(6682):280-4 [9607767] Arch Virol. 1998;143(12):2421-30 [9930197] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5345-9 [202952] J Biol Chem. 1978 Aug 10;253(15):5263-6 [209034] J Gen Virol. 1978 Nov;41(2):443-6 [569187] Proc Natl Acad Sci U S A. 1978 Oct;75(10):4868-72 [217003] J Gen Virol. 1980 Mar;47(1):215-20 [7365464] Biochim Biophys Acta. 1980 Jun 27;608(1):39-46 [6901506] Eur J Biochem. 1980;107(1):39-45 [7398638] J Mol Biol. 1982 May 5;157(1):105-32 [7108955] J Virol. 1984 May;50(2):579-86 [6323757] Virology. 1986 Feb;149(1):114-27 [3004023] FEBS Lett. 1989 Jan 30;243(2):103-14 [2645167] Annu Rev Microbiol. 1990;44:603-23 [2252396] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a new quantitative trait locus on chromosome 7 controlling disease severity of collagen-induced arthritis in rats. AN - 69886413; 10398805 AB - Autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, and multiple sclerosis, are regulated by multiple genes. Major histocompatibility complex (MHC) genes have the strongest effects, but non-MHC genes also contribute to disease susceptibility/severity. In this paper, we describe a new non-MHC quantitative trait locus, Cia8, on rat Chromosome (Chr) 7 that controls collagen-induced arthritis severity in F2 progeny of DA and F344 inbred rats, and present an updated localization of Cia4 on the same chromosome. We also describe the location of mouse and human genes, orthologous to the genes in the genomic intervals containing Cia4 and Cia8, and provide evidence that the segment of rat Chr 7 containing Cia4 and Cia8 is homologous to segments of mouse Chr 10 and 15 and human Chr 8, 12, and 19. JF - Immunogenetics AU - Dracheva, S V AU - Remmers, E F AU - Gulko, P S AU - Kawahito, Y AU - Longman, R E AU - Reese, V R AU - Cannon, G W AU - Griffiths, M M AU - Wilder, R L AD - Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes Of Health, Bldg. 10, Room 9N240, 10 Center Drive MSC 1820, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 787 EP - 791 VL - 49 IS - 9 SN - 0093-7711, 0093-7711 KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - Severity of Illness Index KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Lod Score KW - Humans KW - Mice KW - Sequence Homology KW - Collagen -- adverse effects KW - Chromosome Mapping KW - Genes, MHC Class II KW - Arthritis, Experimental -- genetics KW - Chromosomes, Human, Pair 7 KW - Arthritis, Experimental -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69886413?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunogenetics&rft.atitle=Identification+of+a+new+quantitative+trait+locus+on+chromosome+7+controlling+disease+severity+of+collagen-induced+arthritis+in+rats.&rft.au=Dracheva%2C+S+V%3BRemmers%2C+E+F%3BGulko%2C+P+S%3BKawahito%2C+Y%3BLongman%2C+R+E%3BReese%2C+V+R%3BCannon%2C+G+W%3BGriffiths%2C+M+M%3BWilder%2C+R+L&rft.aulast=Dracheva&rft.aufirst=S&rft.date=1999-08-01&rft.volume=49&rft.issue=9&rft.spage=787&rft.isbn=&rft.btitle=&rft.title=Immunogenetics&rft.issn=00937711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-07 N1 - Date created - 1999-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An avian sarcoma/leukosis virus-based gene trap vector for mammalian cells. AN - 69885936; 10400793 AB - RCASBP-M2C is a retroviral vector derived from an avian sarcoma/leukosis virus which has been modified so that it uses the envelope gene from an amphotropic murine leukemia virus (E. V. Barsov and S. H. Hughes, J. Virol. 70:3922-3929, 1996). The vector replicates efficiently in avian cells and infects, but does not replicate in, mammalian cells. This makes the vector useful for gene delivery, mutagenesis, and other applications in mammalian systems. Here we describe the development of a derivative of RCASBP-M2C, pGT-GFP, that can be used in gene trap experiments in mammalian cells. The gene trap vector pGT-GFP contains a green fluorescent protein (GFP) reporter gene. Appropriate insertion of the vector into genes causes GFP expression; this facilitates the rapid enrichment and cloning of the trapped cells and provides an opportunity to select subpopulations of trapped cells based on the subcellular localization of GFP. With this vector, we have generated about 90 gene-trapped lines using D17 and NIH 3T3 cells. Five trapped NIH 3T3 lines were selected based on the distribution of GFP in cells. The cellular genes disrupted by viral integration have been identified in four of these lines by using a 5' rapid amplification of cDNA ends protocol. JF - Journal of virology AU - Zheng, X H AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 6946 EP - 6952 VL - 73 IS - 8 SN - 0022-538X, 0022-538X KW - Luminescent Proteins KW - 0 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Mammals KW - Genes, Reporter KW - Mice KW - Genetic Vectors KW - Avian Leukosis Virus KW - Avian Sarcoma Viruses -- genetics KW - Luminescent Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69885936?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=An+avian+sarcoma%2Fleukosis+virus-based+gene+trap+vector+for+mammalian+cells.&rft.au=Zheng%2C+X+H%3BHughes%2C+S+H&rft.aulast=Zheng&rft.aufirst=X&rft.date=1999-08-01&rft.volume=73&rft.issue=8&rft.spage=6946&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6 [286319] Cell Growth Differ. 1996 Oct;7(10):1393-401 [8891343] J Biol Chem. 1982 Jun 10;257(11):6461-9 [7076678] Virology. 1984 Jul 15;136(1):89-99 [6330999] J Virol. 1987 Oct;61(10):3004-12 [3041020] J Virol. 1988 Dec;62(12):4809-12 [2460645] Nature. 1989 Mar 9;338(6211):153-6 [2563902] J Virol. 1991 Jul;65(7):3728-37 [2041092] Genes Dev. 1992 Jun;6(6):903-18 [1592261] Cell. 1992 Nov 27;71(5):865-73 [1423634] Kidney Int. 1992 Oct;42(4):888-95 [1333548] Cell. 1993 Sep 24;74(6):1043-51 [8402880] Science. 1994 Feb 11;263(5148):802-5 [8303295] Virology. 1994 Sep;203(2):211-20 [8053145] Genes Dev. 1994 May 1;8(9):1087-105 [7926789] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11241-5 [7972042] Dev Biol. 1995 Jun;169(2):770-4 [7781915] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6592-6 [7604039] Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7036-40 [7624365] Dev Biol. 1995 Sep;171(1):123-9 [7556889] Mol Cell Biol. 1996 Jan;16(1):414-21 [8524323] Development. 1997 Mar;124(6):1133-7 [9102300] FEBS Lett. 1997 May 5;407(3):313-9 [9175875] Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6267-72 [9177206] Dev Biol. 1997 May 15;185(2):201-14 [9187083] Dev Biol. 1997 Jul 1;187(1):36-42 [9224672] Dev Genet. 1997;20(4):338-47 [9254908] Development. 1997 Oct;124(20):4105-11 [9374406] Dev Biol. 1997 Dec 15;192(2):289-99 [9441668] Nature. 1998 Apr 9;392(6676):608-11 [9560157] J Cell Sci. 1998 Sep;111 ( Pt 17):2575-85 [9701556] Virology. 1998 Sep 1;248(2):295-304 [9721238] Virology. 1998 Sep 1;248(2):305-11 [9721239] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13042-7 [9789037] Mol Pharmacol. 1992 Aug;42(2):217-26 [1513321] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4931-6 [8643506] J Virol. 1996 Jun;70(6):3922-9 [8648729] Gene. 1996;173(1 Spec No):99-103 [8707063] Nature. 1979 Nov 15;282(5736):339-41 [228201] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of three nonoxynol-9 preparations on vaginal flora and epithelium. AN - 69883611; 10395859 AB - To evaluate the effects of nonoxynol-9 (N-9) on the vaginal flora and epithelium, 48 women (16 in each group) were evaluated by use of quantitative vaginal cultures and colposcopy. at baseline and at 0.5, 4, 24, 48, and 72 h after insertion of one of three N-9 preparations (4% gel [Conceptrol], 3.5% gel [Advantage-24], or a 28% vaginal contraceptive film). The proportion positive for H2O2+ or H2O2- lactobacilli did not change significantly with any of the preparations, but lactobacilli concentrations decreased transiently. Both the proportion of women with Gardnerella vaginalis and the concentration of G. vaginalis decreased transiently. The proportion of women with Escherichia coli increased with the 4% gel, and the concentration increased with all preparations. The number with anaerobic gram-negative rods increased, although the concentrations decreased. Symptoms and colposcopic abnormalities were rare. Changes in levels of vaginal bacteria were transient after single applications of N-9, but adverse effects may be enhanced with frequent, chronic use. JF - The Journal of infectious diseases AU - Watts, D H AU - Rabe, L AU - Krohn, M A AU - Aura, J AU - Hillier, S L AD - Pediatric, Adolescent, Maternal AIDS Branch, CRMC/NICHD/NIH, Bethesda, MD 20892, USA. hw59i@nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 426 EP - 437 VL - 180 IS - 2 SN - 0022-1899, 0022-1899 KW - Spermatocidal Agents KW - 0 KW - Nonoxynol KW - 26027-38-3 KW - Abridged Index Medicus KW - Index Medicus KW - Enterococcus -- isolation & purification KW - Gram-Negative Anaerobic Bacteria -- drug effects KW - Lactobacillus -- drug effects KW - Humans KW - Enterococcus -- drug effects KW - Epithelium -- drug effects KW - Gram-Negative Anaerobic Bacteria -- isolation & purification KW - Gardnerella vaginalis -- isolation & purification KW - Escherichia coli -- isolation & purification KW - Adult KW - Escherichia coli -- drug effects KW - Gardnerella vaginalis -- drug effects KW - Lactobacillus -- isolation & purification KW - Colposcopy KW - Female KW - Spermatocidal Agents -- pharmacology KW - Vagina -- cytology KW - Bacteria -- isolation & purification KW - Bacteria -- drug effects KW - Nonoxynol -- pharmacology KW - Vagina -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69883611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=The+effects+of+three+nonoxynol-9+preparations+on+vaginal+flora+and+epithelium.&rft.au=Watts%2C+D+H%3BRabe%2C+L%3BKrohn%2C+M+A%3BAura%2C+J%3BHillier%2C+S+L&rft.aulast=Watts&rft.aufirst=D&rft.date=1999-08-01&rft.volume=180&rft.issue=2&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-07 N1 - Date created - 1999-09-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Recall of a lead-contaminated vitamin and mineral supplement in a clinical trial. AN - 69540739; 15073911 AB - The Treatment of Lead-exposed Children (TLC) trial tested whether developmental outcome differed between children treated for lead poisoning with succimer or placebo. On 7 July 1997, TLC was informed that the vitamin and mineral supplements it gave to all children were contaminated with about 35 microg of lead per tablet. TLC recalled the contaminated supplements and measured the children's exposure. The families of 96% of the children were contacted with 30 days. Among the 571 children to whom the contaminated supplements were dispensed, the mean increase in blood lead was 0.06+/-0.01 micromol/L (1.2+/-0.2 microg/dL); among 78 children to whom they were not, it was 0.09+/-0.03 micromol/L (1.8+/-0.7 microg/dL). There was no evidence of a dose-response relation between estimated supplement consumption and increase in blood lead concentration. The children's blood lead concentrations were not detectably affected by the contamination. Since the association of cognitive delay with lead exposure is best described for blood lead, we believe that the trial's inference about the effect of drug therapy on lead induced cognitive delay should be unaffected. Copyright 1999 John Wiley & Sons, Ltd. JF - Pharmacoepidemiology and drug safety AU - Rogan, W J AU - Ragan, N B AU - Damokosh, A I AU - Davoli, C AU - Shaffer, T R AU - Jones, R L AU - Wilkens, S AU - Heenehan, M C AU - Ware, J H AU - Henretig, F AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 343 EP - 350 VL - 8 IS - 5 SN - 1053-8569, 1053-8569 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69540739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacoepidemiology+and+drug+safety&rft.atitle=Recall+of+a+lead-contaminated+vitamin+and+mineral+supplement+in+a+clinical+trial.&rft.au=Rogan%2C+W+J%3BRagan%2C+N+B%3BDamokosh%2C+A+I%3BDavoli%2C+C%3BShaffer%2C+T+R%3BJones%2C+R+L%3BWilkens%2C+S%3BHeenehan%2C+M+C%3BWare%2C+J+H%3BHenretig%2C+F&rft.aulast=Rogan&rft.aufirst=W&rft.date=1999-08-01&rft.volume=8&rft.issue=5&rft.spage=343&rft.isbn=&rft.btitle=&rft.title=Pharmacoepidemiology+and+drug+safety&rft.issn=10538569&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-07-12 N1 - Date created - 2004-04-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Data needs for occupational epidemiologic studies. AN - 69505054; 11529156 AB - Data needs in an epidemiologic study can appear to be substantial in light of the other responsibilities of an industrial hygienist. Many of the data needed for this type of investigation, however, are already collected for other exposure assessment purposes. To increase understanding of this concept, the data needs for the major purposes for conducting an exposure assessment are identified. The purposes include determining compliance; implementing industrial hygiene programs, such as personal protective and respiratory equipment, hazard communication training, and medical surveillance; investigating health complaints and worker concerns; investigating tasks or engineering control effectiveness; investigating toxic tort or worker compensation claims; and conducting epidemiologic studies. A comprehensive exposure assessment system is then described that incorporates the data needs for all these purposes, including epidemiologic studies. The data needs of epidemiologic studies and how the data are used are then described and illustrated with examples taken from published epidemiologic studies. JF - Journal of environmental monitoring : JEM AU - Stewart, P AU - Stenzel, M AD - National Cancer Institute, EPS 810, Bethesda, MD 20892, USA. Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 75N EP - 82N VL - 1 IS - 4 SN - 1464-0325, 1464-0325 KW - Index Medicus KW - Protective Clothing KW - Guideline Adherence KW - Epidemiologic Studies KW - Humans KW - Workers' Compensation KW - Data Collection KW - Workplace KW - Research Design KW - Occupational Health KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69505054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+environmental+monitoring+%3A+JEM&rft.atitle=Data+needs+for+occupational+epidemiologic+studies.&rft.au=Stewart%2C+P%3BStenzel%2C+M&rft.aulast=Stewart&rft.aufirst=P&rft.date=1999-08-01&rft.volume=1&rft.issue=4&rft.spage=75N&rft.isbn=&rft.btitle=&rft.title=Journal+of+environmental+monitoring+%3A+JEM&rft.issn=14640325&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-09-13 N1 - Date created - 2001-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Second malignancies as a consequence of nucleoside analog therapy for chronic lymphoid leukemias. AN - 69283681; 10561309 AB - The nucleoside analogs fludarabine, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CdA), commonly used in the treatment of patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), are associated with myelosuppression and profound and prolonged immunosuppression. These complications raise the possibility of an increase in secondary malignancies in patients whose disease already places them at greater risk. The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA. We reviewed the long-term follow-up data for 2,014 patients treated on National Cancer Institute Group C protocols with fludarabine for relapsed and refractory CLL and with DCF and CdA for HCL using a Second Cancer Report. The numbers of observed and expected secondary tumors were compared. Median follow-up periods for the DCF (n = 409), fludarabine (n = 724), and CdA (n = 979) studies were 6.9, 7.4, and 5.1 years, respectively. The 111 malignancies were most commonly lymphoma (25 patients), prostate (19), lung (15), colorectal (nine), bladder (six), and breast (six), but also CNS, stomach, ovary, head and neck, melanoma, sarcoma, testicular, and myeloid leukemias. Compared with age-adjusted 1994 Surveillance and Epidemiology End-Results rates for the general population, the observed/expected frequencies for DCF, fludarabine, and CdA were 1.43 (95% confidence interval [CI], 0.93 to 2.10), 1.65 (95% CI, 1.04 to 2.47), and 1.50 (95% CI, 1.14 to 1.93), respectively, indicating a significant (at P =.05) increase in risk for patients treated on the latter two protocols compared with a normal population. However, these values are consistent with the increase already associated with these diseases. Despite their immunosuppression, nucleoside analogs can be safely administered to patients with CLL or HCL without a significantly increased risk of secondary malignancies. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Cheson, B D AU - Vena, D A AU - Barrett, J AU - Freidlin, B AD - The Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. chesonb@ctep.nci.nih.gov Y1 - 1999/08// PY - 1999 DA - August 1999 SP - 2454 EP - 2460 VL - 17 IS - 8 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Immunosuppressive Agents KW - Pentostatin KW - 395575MZO7 KW - Cladribine KW - 47M74X9YT5 KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Humans KW - Aged KW - Middle Aged KW - Follow-Up Studies KW - Male KW - Female KW - Vidarabine -- analogs & derivatives KW - Neoplasms, Second Primary -- etiology KW - Cladribine -- therapeutic use KW - Leukemia, Lymphocytic, Chronic, B-Cell -- complications KW - Vidarabine -- adverse effects KW - Pentostatin -- therapeutic use KW - Antineoplastic Agents -- adverse effects KW - Cladribine -- adverse effects KW - Immunosuppression -- adverse effects KW - Leukemia, Lymphocytic, Chronic, B-Cell -- drug therapy KW - Pentostatin -- adverse effects KW - Vidarabine -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69283681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Second+malignancies+as+a+consequence+of+nucleoside+analog+therapy+for+chronic+lymphoid+leukemias.&rft.au=Cheson%2C+B+D%3BVena%2C+D+A%3BBarrett%2C+J%3BFreidlin%2C+B&rft.aulast=Cheson&rft.aufirst=B&rft.date=1999-08-01&rft.volume=17&rft.issue=8&rft.spage=2454&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-01-06 N1 - Date created - 2000-01-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacterial death induced by expression of the intracellular portion of human Fas AN - 17939435; 5200217 AB - In attempting to produce the intracellular portion of human Fas (IC sub(175-319)) as a GST-fusion protein we found that expression of GST-IC sub(175-319)), but not GST alone or GST-IC sub(231-298) (containing the Fas death domain), rapidly caused the death of host E. coli cells. Expression of GST-IC sub(175-319) with a single amino acid substitution (V238N) corresponding to the mouse lpr super(cg) mutation, or E245A, which abolishes the ability of Fas to self-associate, did not kill bacteria. Deletional analysis identified a 20-amino acids region (Asp sub(210)-Lys sub(230)) as essential for the killing activity, and introduction of a single amino acid substitution (T225P) in this 20 amino acid region markedly decreased the ability of Fas- IC sub(175-319) to cause bacterial death. These data indicate that Fas can deliver a death signal in prokaryotic organisms by a means that shares some features with eukaryotic cells, and raise the possibility that certain mechanisms leading to programmed cell death may be conserved from bacteria to mammalian cells. JF - Cell Death and Differentiation AU - Yang, Y AU - Hong, J S AU - Eder, A AU - Ashwell, J D AD - Building 10, Room 1B-40, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 805 EP - 812 VL - 6 IS - 8 SN - 1350-9047, 1350-9047 KW - Fas antigen KW - Microbiology Abstracts B: Bacteriology KW - Apoptosis KW - Escherichia coli KW - Amino acid composition KW - Fusion protein KW - Signal transduction KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17939435?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+Death+and+Differentiation&rft.atitle=Bacterial+death+induced+by+expression+of+the+intracellular+portion+of+human+Fas&rft.au=Yang%2C+Y%3BHong%2C+J+S%3BEder%2C+A%3BAshwell%2C+J+D&rft.aulast=Yang&rft.aufirst=Y&rft.date=1999-08-01&rft.volume=6&rft.issue=8&rft.spage=805&rft.isbn=&rft.btitle=&rft.title=Cell+Death+and+Differentiation&rft.issn=13509047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Fusion protein; Apoptosis; Amino acid composition; Signal transduction ER - TY - JOUR T1 - Effect of 13 week magnetic field exposures on DMBA-initiated mammary gland carcinomas in female Sprague-Dawley rats AN - 17913472; 5172027 AB - Several studies suggest that exposure to 50 Hz magnetic fields may promote chemically induced breast cancer in rats. Groups of 100 female Sprague-Dawley rats were initiated with four weekly 5 mg gavage doses of 7,12-dimethylbenz[a]anthracene (DMBA) starting at 50 days of age. After the first weekly DMBA administration, exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 G field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week was initiated. Exposure continued for 13 weeks. A vehicle control group without DMBA was included. In a second study, using lower doses of DMBA, groups of 100 female Sprague-Dawley rats were initiated with four weekly doses of 2 mg of DMBA starting at 50 days of age followed, after the first weekly DMBA administration, by exposure to ambient fields (sham exposed) or 50 Hz magnetic fields at either 1 or 5 G field intensity for 18.5 h/day, 7 days/week for 13 weeks. Rats were weighted and palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or on the time of appearance of mammary tumors in either study. At the end of 13 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. In the first 13 week study, the mammary gland carcinoma incidences were 92, 86, 96 and 96% for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. The total numbers of carcinomas were 691, 528 (P < 0.05, decrease), 561 and 692 for the DMBA controls, 1 G, 50 Hz, 5 G, 50 Hz and 1 G, 60 Hz groups, respectively. In study 2, the mammary gland carcinoma incidences were 43, 48 and 38% for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. The total numbers of carcinomas were 102, 90 and 79 for the DMBA controls, 1 G, 50 Hz and 5 G, 50 Hz groups, respectively. There was no effect of magnetic field exposure on tumor size either by in-life palpation or by measurement at necropsy in either study. There was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer in these studies in female rats. These studies do not support the hypothesis that magnetic field exposure promotes breast cancer in this DMBA rat model. JF - Carcinogenesis AU - Anderson, LE AU - Boorman, G A AU - Morris, JE AU - Sasser, L B AU - Mann, P C AU - Grumbein, S L AU - Hailey, J R AU - McNally, A AU - Sills, R C AU - Haseman, J K AD - National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, boorman@niehs.nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 1615 EP - 1620 VL - 20 IS - 8 SN - 0143-3334, 0143-3334 KW - rats KW - Toxicology Abstracts KW - Magnetic fields KW - Mammary gland KW - 9,10-Dimethyl-1,2-benzanthracene KW - Carcinoma KW - X 24210:Radiation & radioactive materials UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17913472?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effect+of+13+week+magnetic+field+exposures+on+DMBA-initiated+mammary+gland+carcinomas+in+female+Sprague-Dawley+rats&rft.au=Anderson%2C+LE%3BBoorman%2C+G+A%3BMorris%2C+JE%3BSasser%2C+L+B%3BMann%2C+P+C%3BGrumbein%2C+S+L%3BHailey%2C+J+R%3BMcNally%2C+A%3BSills%2C+R+C%3BHaseman%2C+J+K&rft.aulast=Anderson&rft.aufirst=LE&rft.date=1999-08-01&rft.volume=20&rft.issue=8&rft.spage=1615&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Magnetic fields; Mammary gland; Carcinoma; 9,10-Dimethyl-1,2-benzanthracene ER - TY - JOUR T1 - Laxifloranone, a New Phloroglucinol Derivative from Marila laxiflora AN - 17502372; 4691008 AB - A new polyisoprenylated phloroglucinol derivative has been isolated from the twigs of Marila laxiflora and characterized on the basis of 1D and 2D NMR spectra. Laxifloranone (1) shows moderate inhibition of the cytopathic effects of in vitro HIV infection. JF - Journal of Natural Products AU - Bokesch, H R AU - Groweiss, A AU - McKee, T C AU - Boyd, M R AD - Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA, boyd@dtpax2.ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 1197 EP - 1199 VL - 62 IS - 8 SN - 0163-3864, 0163-3864 KW - HIV KW - laxifloranone KW - phloroglucinol KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology KW - Antiviral agents KW - Human immunodeficiency virus KW - Inhibition KW - Marila laxiflora KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17502372?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Natural+Products&rft.atitle=Laxifloranone%2C+a+New+Phloroglucinol+Derivative+from+Marila+laxiflora&rft.au=Bokesch%2C+H+R%3BGroweiss%2C+A%3BMcKee%2C+T+C%3BBoyd%2C+M+R&rft.aulast=Bokesch&rft.aufirst=H&rft.date=1999-08-01&rft.volume=62&rft.issue=8&rft.spage=1197&rft.isbn=&rft.btitle=&rft.title=Journal+of+Natural+Products&rft.issn=01633864&rft_id=info:doi/10.1021%2Fnp990136e LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Marila laxiflora; Human immunodeficiency virus; Antiviral agents; Inhibition DO - http://dx.doi.org/10.1021/np990136e ER - TY - JOUR T1 - Characterization of Novel Macrolide Toxins, Mycolactones A and B, from a Human Pathogen, Mycobacterium ulcerans AN - 17440355; 4655738 AB - Mycobacterium ulcerans causes a severe skin disease, Buruli ulcer characterized by extensive necrosis in the absence of an acute inflammatory response. Even though the better known pathogenic members of the genus Mycobacterium, such as Mycobacterium tuberculosis and Mycobacterium leprae, are not associated with toxins, the possible presence of a toxin in M. ulcerans, which is an extracellular pathogen, has been hypothesized for a number of years. Despite several attempts, no compound responsible for the cytopathic effect of this organism has been identified. Partial purification of the toxin and evidence that it was a lipophilic molecule were reported earlier. The spectral analyses of the toxin lead to the identification of two compounds which were named mycolactones A and B. The structure elucidation of the two compounds is described in this paper. This is the first identification of a macrolide produced by a human pathogen, as well as the only macrolide identified in the genus Mycobacterium. JF - Journal of the American Chemical Society AU - Gunawardana, G AU - Chatterjee, D AU - George, K M AU - Brennan, P AU - Whittern, D AU - Small, PLC AD - Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60046-3500, Rocky Mountain Laboratories, NIH, NIA1D, 903 South Fourth Street, Hamilton, MT 59840, USA, psmall@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 6092 EP - 6093 PB - American Chemical Society VL - 121 IS - 25 SN - 0002-7863, 0002-7863 KW - mycolactone A KW - mycolactone B KW - structure KW - macrolides KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Necrosis KW - Mycobacterium ulcerans KW - Skin diseases KW - Buruli ulcer KW - Toxins KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17440355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=Characterization+of+Novel+Macrolide+Toxins%2C+Mycolactones+A+and+B%2C+from+a+Human+Pathogen%2C+Mycobacterium+ulcerans&rft.au=Gunawardana%2C+G%3BChatterjee%2C+D%3BGeorge%2C+K+M%3BBrennan%2C+P%3BWhittern%2C+D%3BSmall%2C+PLC&rft.aulast=Gunawardana&rft.aufirst=G&rft.date=1999-08-01&rft.volume=121&rft.issue=25&rft.spage=6092&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/10.1021%2Fja990017l LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium ulcerans; Skin diseases; Buruli ulcer; Necrosis; Toxins DO - http://dx.doi.org/10.1021/ja990017l ER - TY - JOUR T1 - EIIaCre - Utility of a general deleter strain AN - 17438703; 4645745 AB - We conducted a survey of the utility of the EllaCre strain of transgenic mice in which Cre is expressed in the unfertilized egg and in the zygote. Our survey is based on results reported by 10 laboratories that set up matings of EllaCre mice and gene-altered mutant strains that harbor lox-flanked genes. Cre action on 29 different lox-flanked loci resulted in progeny in which the DNA sequences between the lox sites were found to be deleted. In cases where proper quantitation was performed, the frequency of deletions approximated Mendelian expectations. These results underscore the utility of EllaCre mice as a general deleter strain. This review examines the efficiency of Cre mediated deletion of DNA sequences in genetically altered mice. JF - Transgenic Research AU - Williams-Simons, L AU - Westphal, H AD - Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD 20892-2790 USA, hw@helix.nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 253 EP - 254 VL - 8 IS - 4 SN - 0962-8819, 0962-8819 KW - Nucleotide sequence KW - mice KW - Cre protein KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Reviews KW - Transgenic mice KW - W2 32070:Animals KW - W2 32000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17438703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Transgenic+Research&rft.atitle=EIIaCre+-+Utility+of+a+general+deleter+strain&rft.au=Williams-Simons%2C+L%3BWestphal%2C+H&rft.aulast=Williams-Simons&rft.aufirst=L&rft.date=1999-08-01&rft.volume=8&rft.issue=4&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Transgenic+Research&rft.issn=09628819&rft_id=info:doi/10.1023%2FA%3A1008994831937 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transgenic mice; Reviews DO - http://dx.doi.org/10.1023/A:1008994831937 ER - TY - JOUR T1 - Residential exposure to magnetic fields: an empirical examination of alternative measurement strategies AN - 17435116; 4653289 AB - The objectives were to investigate the impact of measuring a single home then imputing information from another home among subjects who lived in two homes in a subset of the National Cancer Institute/Children's Cancer Group (NCI/CCG) investigation of residential exposure to magnetic fields and risk of childhood leukaemia. Each subject's summary time weighted average (TWA) exposure was derived from measurements of two homes, weighted by the fraction of the reference period lived in the residence. The three cost efficient field work strategies examined were measuring: (a) the longer lived in home; (b) the currently lived in home; and (c) the former lived in home. Two different methods were used for imputing the missing values: (a) control mean imputation, (b) status specific mean imputation. The subject's summary exposure to magnetic fields estimated with each approach was compared with the subject's TWA calculated from measurements in both homes. The association between estimated exposure to magnetic fields and the risk of leukaemia under different approaches was examined with unconditional logistic regression analysis. The Pearson correlation coefficient between the two measurements within subjects was 0.31 (p<10 super(-4)), indicating a lack of independence of measurements. Differences were found between mean exposures in current and former homes of cases, and between longer and shorter lived in homes of controls. All methods with measurements from one of the homes in conjunction with imputation of measurements for the second home led to marked attenuation of risk estimates at the highest exposure category, particularly when measurements from current homes were used and those from former homes were imputed. Results argue against attempting to estimate lifetime magnetic field exposure from imputed values derived from current residences to fill in gaps caused by unmeasured residences previously lived in. JF - Occupational and Environmental Medicine AU - Baris, D AU - Linet AU - Tarone, R E AU - Kleinerman, R A AU - Hatch, EE AU - Kaune, W T AU - Robison, L L AU - Lubin, J AU - Wacholder, S AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Executive Plaza South, Room-8122, Bethesda, MD 20892-7240, USA, barisd@epndce.nci.nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 562 EP - 566 VL - 56 IS - 8 SN - 1351-0711, 1351-0711 KW - magnetic fields KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Houses KW - Dosimetry KW - Children KW - Cancer KW - Public health KW - Magnetic fields KW - Leukemia KW - Radiation KW - Regression analysis KW - Residential areas KW - X 24210:Radiation & radioactive materials KW - H 11000:Diseases/Injuries/Trauma UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17435116?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Occupational+and+Environmental+Medicine&rft.atitle=Residential+exposure+to+magnetic+fields%3A+an+empirical+examination+of+alternative+measurement+strategies&rft.au=Baris%2C+D%3BLinet%3BTarone%2C+R+E%3BKleinerman%2C+R+A%3BHatch%2C+EE%3BKaune%2C+W+T%3BRobison%2C+L+L%3BLubin%2C+J%3BWacholder%2C+S&rft.aulast=Baris&rft.aufirst=D&rft.date=1999-08-01&rft.volume=56&rft.issue=8&rft.spage=562&rft.isbn=&rft.btitle=&rft.title=Occupational+and+Environmental+Medicine&rft.issn=13510711&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Residential areas; Children; Cancer; Leukemia; Public health; Magnetic fields; Radiation; Houses; Dosimetry; Regression analysis; Risk assessment ER - TY - JOUR T1 - Papuamides A-D, HIV-Inhibitory and Cytotoxic Depsipeptides from the Sponges Theonella mirabilis and Theonella swinhoei Collected in Papua New Guinea AN - 17435093; 4655734 AB - The novel cyclic depsipeptides papuamides A (1), B (2), C (3), and D (4) have been isolated from Papua New Guinea collections of the sponges Theonella mirabilis and Theonella swinhoei. Their structures were determined by a combination of spectroscopic analysis and chemical degradation and derivatization studies. In addition to glycine, alanine, and threonine, these peptides contain a number of unusual amino acids including 3,4-dimethylglutamine, beta -methoxytyrosine, 3-methoxyalanine, and 2,3-diaminobutanoic acid or 2-amino-2-butenoic acid residues. Papuamides A-D (1-4) are also the first marine-derived peptides reported to contain 3-hydroxyleucine and homoproline residues. These peptides also contain a previously undescribed 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid moiety N-linked to a terminal glycine residue. Papuamides A (1) and B (2) inhibited the infection of human T-lymphoblastoid cells by HIV-1 sub(RF) in vitro with an EC sub(50) of approximately 4 ng/mL. Compound 1 was also cytotoxic against a panel of human cancer cell lines with a mean IC sub(50) of 75 ng/mL. JF - Journal of the American Chemical Society AU - Ford, P W AU - Gustafson, K R AU - McKee, T C AU - Shigematsu, Nobuharu AU - Maurizi, L K AU - Pannell, L K AU - Williams, DE AU - De Silva, ED AU - Lassota, P AU - Allen, T M AU - Van Soest, R AU - Andersen, R J AU - Boyd, M R AD - Frederick Cancer Research and Development Center, National Cancer Institute, Building 1052, Room 121, Frederick, MD 21702-1201, USA, boyd@dtpax2.ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 5899 EP - 5909 PB - American Chemical Society VL - 121 IS - 25 SN - 0002-7863, 0002-7863 KW - HIV-1 KW - cyclic depsipeptides KW - cyclic depsipeptides papuamides KW - Virology & AIDS Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; ASFA Marine Biotechnology Abstracts; ASFA 1: Biological Sciences & Living Resources KW - Molecular structure KW - Cytotoxicity KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Theonella mirabilis KW - ISEW, Papua New Guinea KW - Peptides KW - Theonella swinhoei KW - Tumor cells KW - Antitumour agents KW - A 01068:Antiviral & viricidal KW - Q1 08625:Non-edible products KW - Q4 27380:Pharmaceuticals KW - V 22100:Antiviral agents UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17435093?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=Papuamides+A-D%2C+HIV-Inhibitory+and+Cytotoxic+Depsipeptides+from+the+Sponges+Theonella+mirabilis+and+Theonella+swinhoei+Collected+in+Papua+New+Guinea&rft.au=Ford%2C+P+W%3BGustafson%2C+K+R%3BMcKee%2C+T+C%3BShigematsu%2C+Nobuharu%3BMaurizi%2C+L+K%3BPannell%2C+L+K%3BWilliams%2C+DE%3BDe+Silva%2C+ED%3BLassota%2C+P%3BAllen%2C+T+M%3BVan+Soest%2C+R%3BAndersen%2C+R+J%3BBoyd%2C+M+R&rft.aulast=Ford&rft.aufirst=P&rft.date=1999-08-01&rft.volume=121&rft.issue=25&rft.spage=5899&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/10.1021%2Fja990582o LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Molecular structure; Antiviral agents; Peptides; Antitumour agents; Cytotoxicity; Tumor cells; Human immunodeficiency virus 1; Theonella mirabilis; Theonella swinhoei; ISEW, Papua New Guinea DO - http://dx.doi.org/10.1021/ja990582o ER - TY - JOUR T1 - Cadmium(II), unlike nickel(II), inhibits 8-oxo-dGTPase activity and increases 8-oxo-dG level in DNA of the rat testis, a target organ for cadmium(II) carcinogenesis AN - 17402769; 4623045 AB - 8-Oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) is an enzyme which prevents incorporation into DNA of promutagenic 8-oxo-2'-deoxyguanosine (8-oxo-dG) from a deoxynucleotide pool damaged by endogenous oxidants. Its inhibition may thus be carcinogenic. We previously found that Cd(II) inhibited 8-oxo-dGTPase in both cell free systems and cultured cells. To verify this finding in a relevant animal model, we investigated the effects of Cd(II) on cellular 8-oxo-dGTPase activity and nuclear DNA 8-oxo-dG levels in the rat testis, a target organ for Cd(II) carcinogenesis. Ni(II), which does not induce testicular tumors in rats and is a weaker in vitro inhibitor of 8-oxo-dGTPase than Cd(II), was investigated as a comparison. Male F344/NCr rats were given a single s.c. dose of 20 mu mol Cd(II) acetate, 90 mu mol Ni(II) acetate or 180 mu mol sodium acetate (controls) per kg body wt and killed 2, 8, 24 or 48 h later (three rats/time point). Cd(II) caused a gradual decrease in testicular 8-oxo-dGTPase activity with time. It became significant only after 8 h post-injection (P < 0.05) and resulted in a final 50% loss of the enzyme activity at 48 h (P < 0.01). Although the results for Ni(II) at 8 h and later were apparently lower than the controls, the decrease did not reach statistical significance. Treatment of rats with Cd(II) led to an early and progressive increase (from 130% at 2 h to 200% at 48 h versus the controls) of the 8-oxo-dG level in testicular DNA (P < 0.05 or better). Ni(II) acetate also tended to raise the testicular 8-oxo-dG level, but the increase was transient, with an apparent maximum at 8 h, and did not approach statistical significance (P < 0.2). Thus, Cd(II), unlike Ni(II), is able to inhibit 8-oxo-dGTPase activity and to raise 8-oxo-dG levels in rat testicular DNA. However, the time course of both effects indicates that 8-oxo-dGTPase inhibition is most likely not the sole cause of the increase in 8-oxo-dG. JF - Carcinogenesis AU - Bialkowski, K AU - Bialkowska, A AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute and SAIC Frederick, FCRDC, Frederick, MD 21702, USA, kasprkaz@mail.ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 1621 EP - 1624 VL - 20 IS - 8 SN - 0143-3334, 0143-3334 KW - rats KW - testes KW - 8-oxo-2'-deoxyguanosine KW - 8-oxo-2'-deoxyguanosine 5'-triphosphate KW - cadmium KW - nickel KW - Toxicology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Testes KW - Carcinogenesis KW - N 14630:Chemical reactions & interactions, including effects of radiation KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17402769?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Cadmium%28II%29%2C+unlike+nickel%28II%29%2C+inhibits+8-oxo-dGTPase+activity+and+increases+8-oxo-dG+level+in+DNA+of+the+rat+testis%2C+a+target+organ+for+cadmium%28II%29+carcinogenesis&rft.au=Bialkowski%2C+K%3BBialkowska%2C+A%3BKasprzak%2C+K+S&rft.aulast=Bialkowski&rft.aufirst=K&rft.date=1999-08-01&rft.volume=20&rft.issue=8&rft.spage=1621&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Testes; Carcinogenesis ER - TY - JOUR T1 - Supplement to the Carcinogenic Potency Database (CPDB): Results of Animal Bioassays Published in the General Literature in 1993 to 1994 and by the National Toxicology Program in 1995 to 1996 AN - 17383285; 4603435 AB - The Carcinogenic Potency Database (CPDB) is a systematic and unifying analysis of results of chronic, long-term cancer tests. This paper presents a supplemental plot of the CPDB, including 513 experiments on 157 test compounds published in the general literature in 1993 and 1994 and in Technical Reports of the National Toxicology Program in 1995 and 1996. The plot standardizes the experimental results (whether positive or negative for carcinogenicity), including qualitative data on strain, sex, route of compound administration, target organ, histopathology, and author's opinion and reference to the published paper, as well as quantitative data on carcinogenic potency, statistical significance, tumor incidence, dose-response curve shape, length of experiment, duration of dosing, and dose rate. A numerical description of carcinogenic potency, the TD sub(50), is estimated for each set of tumor incidence data reported. When added to the data published earlier, the CPDB now includes results of 5,620 experiments on 1,372 chemicals that have been reported in 1,250 published papers and 414 National Cancer Institute/National Toxicology Program Technical Reports. The plot presented here includes detailed analyses of 25 chemicals tested in monkeys for up to 32 years by the National Cancer Institute. Half the rodent carcinogens that were tested in monkeys were not carcinogenic, despite usually strong evidence of carcinogenicity in rodents and/or humans. Our analysis of possible explanatory factors indicates that this result is due in part to the fact that the monkey studies lacked power to detect an effect compared to standard rodent bioassays. Factors that contributed to the lack of power are the small number of animals on test; a stop-exposure protocol for model rodent carcinogens; in a few cases, toxic doses that resulted in stoppage of dosing or termination of the experiment; and in a few cases, low doses administered to monkeys or early termination of the experiment even though the doses were not toxic. Among chemicals carcinogenic in both monkeys and rodents, there is some support for target site concordance, but it is primarily restricted to liver tumors. Potency values are highly correlated between rodents and monkeys. The plot in this paper can be used in conjunction with the earlier results published in the CRC Handbook of Carcinogenic Potency and Genotoxicity Databases and with our web site (http://potency.berkeley.edu), which includes a guide to the plot of the database, a complete description of the numerical index of carcinogenic potency (TD sub(50)), and a discussion of the sources of data, the rationale for the inclusion of particular experiments and particular target sites, and the conventions adopted in summarizing the literature. Two summary tables permit easy access to the literature of animal cancer tests by target organ and by chemical. For readers using the CPDB extensively, a combined plot on diskette or other format is available from the first author. It includes all results published earlier and in this paper, ordered alphabetically by chemical. A SAS database is also available. JF - Environmental Health Perspectives AU - Gold, L S AU - Manley, N B AU - Slone, TH AU - Rohrbach, L AD - NIEHS Center, 401 Barker Hall, University of California, Berkeley, CA 94720-3202, USA, lois@potency.berkeley.edu Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 527 EP - 600 VL - 107 SN - 0091-6765, 0091-6765 KW - Toxicology Abstracts KW - Databases KW - Bioassays KW - Laboratory animals KW - Carcinogens KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17383285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Supplement+to+the+Carcinogenic+Potency+Database+%28CPDB%29%3A+Results+of+Animal+Bioassays+Published+in+the+General+Literature+in+1993+to+1994+and+by+the+National+Toxicology+Program+in+1995+to+1996&rft.au=Gold%2C+L+S%3BManley%2C+N+B%3BSlone%2C+TH%3BRohrbach%2C+L&rft.aulast=Gold&rft.aufirst=L&rft.date=1999-08-01&rft.volume=107&rft.issue=&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Databases; Carcinogens; Laboratory animals; Bioassays ER - TY - JOUR T1 - The structure of bacteriorhodopsin: an emerging consensus AN - 17378089; 4589321 AB - Six different sets of coordinates have been recently published for bacteriorhodopsin, with reported resolutions ranging from 3.5 Angstrom to 2.3 Angstrom. Three of these are the result of electron crystallographic investigations of two-dimensional crystals of bacteriorhodopsin, whereas the others are from X-ray crystallographic studies of three-dimensional crystals of bacteriorhodopsin. How similar are these models? Are the structure determinations using X-ray diffraction data more accurate than those determined by electron crystallography? Is any one of these coordinate sets closer to the `real' structure of bacteriorhodopsin than the others? Does the availability of newer models bring us closer to understanding how bacteriorhodopsin really works? These questions, as well as some related issues, are currently being explored. JF - Current Opinion in Structural Biology AU - Subramaniam, S AD - MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK and Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD 20892, USA, sriram@mrc-lmb.cam.ac.uk Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 462 EP - 468 VL - 9 IS - 4 SN - 0959-440X, 0959-440X KW - bacteriorhodopsin KW - Microbiology Abstracts B: Bacteriology KW - Protein structure KW - Photosynthetic pigments KW - Crystallography KW - X-ray diffraction KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17378089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Structural+Biology&rft.atitle=The+structure+of+bacteriorhodopsin%3A+an+emerging+consensus&rft.au=Subramaniam%2C+S&rft.aulast=Subramaniam&rft.aufirst=S&rft.date=1999-08-01&rft.volume=9&rft.issue=4&rft.spage=462&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Structural+Biology&rft.issn=0959440X&rft_id=info:doi/10.1016%2FS0959-440X%2899%2980065-7 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - X-ray diffraction; Crystallography; Protein structure; Photosynthetic pigments DO - http://dx.doi.org/10.1016/S0959-440X(99)80065-7 ER - TY - JOUR T1 - Mortality among aerial pesticide applicators and flight instructors: Follow-up from 1965-1988 AN - 17377555; 4596023 AB - Vital status followup for a retrospective cohort mortality study of 9,961 male aerial pesticide applicators was extended beyond a previous study (1965-1979), through December 31, 1988. Rate ratios (RR) were used to compare directly adjusted mortality rates between applicators and a comparison cohort of 9,969 flight instructors. Standardized mortality ratios (SMR) were calculated for comparisons with the U.S. white male population. Among applicator pilots, there were 1,441 deaths, and among instructors, 1,045. In both groups, aircraft accidents were the major cause of death (446 applicators; 234 instructors). Compared with flight instructors, aerial applicator pilots were at significantly elevated risk for all causes of death (risk ratio = 1.34) and for malignant neoplasms (1.18), non-motor vehicle accidents (1.71), motor vehicle accidents (1.69), and stroke (1.91). Pancreatic cancer (2.71) and leukemia (3.35) were significantly elevated. Applicators were at lower risk of colon cancer (0.51) and multiple myeloma (0.23) mortality. Based on U.S. rates, the SMR for all causes of death among applicators was 111 (95% confidence interval (CI) = 105-117) and among instructors, 81 (CI = 76-85). Aircraft accidents were a major cause of mortality in both applicator and flight instructor cohorts. Several other causes of death, some possibly related to pesticide exposure, were also elevated among pesticide applicator pilots. JF - American Journal of Industrial Medicine AU - Cantor, K P AU - Silberman, W AD - 6120 Executive Blvd., EPS-8106, Bethesda, MD 20892-7240, USA, cantor@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 239 EP - 247 VL - 36 IS - 2 SN - 0271-3586, 0271-3586 KW - man KW - flight instructors KW - Toxicology Abstracts; Health & Safety Science Abstracts; Risk Abstracts KW - Risk assessment KW - Pancreatic carcinoma KW - Pesticide applications KW - Leukemia KW - Occupational exposure KW - Mortality KW - Cancer KW - Pesticides KW - R2 23080:Industrial and labor KW - X 24132:Chronic exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17377555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Mortality+among+aerial+pesticide+applicators+and+flight+instructors%3A+Follow-up+from+1965-1988&rft.au=Cantor%2C+K+P%3BSilberman%2C+W&rft.aulast=Cantor&rft.aufirst=K&rft.date=1999-08-01&rft.volume=36&rft.issue=2&rft.spage=239&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2F%28SICI%291097-0274%28199908%2936%3A23.3.CO%3B2-M LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Occupational exposure; Mortality; Cancer; Leukemia; Pesticides; Pesticide applications; Pancreatic carcinoma DO - http://dx.doi.org/10.1002/(SICI)1097-0274(199908)36:2<239::AID-AJIM3>3.3.CO;2-M ER - TY - JOUR T1 - Occupational risk factors for pancreatic cancer: A case-control study based on death certificates from 24 U.S. states AN - 17376792; 4596025 AB - The relation between occupational exposure and pancreatic cancer is not well established. A population-based case-control study based on death certificates from 24 U.S. states was conducted to determine if occupations/industries or work-related exposures to solvents were associated with pancreatic cancer death. The cases were 63,097 persons who died from pancreatic cancer occurring in the period 1984-1993. The controls were 252,386 persons who died from causes other than cancer in the same time period. Industries associated with significantly increased risk of pancreatic cancer included printing and paper manufacturing; chemical, petroleum, and related processing; transport, communication, and public service; wholesale and retail trades; and medical and other health-related services. Occupations associated with significantly increased risk included managerial, administrative, and other professional occupations; technical occupations; and sales, clerical, and other administrative support occupations. Potential exposures to formaldehyde and other solvents were assessed by using a job exposure matrix developed for this study. Occupational exposure to formaldehyde was associated with a moderately increased risk of pancreatic cancer, with ORs of 1.2, 1.2, 1.4 for subjects with low, medium, and high probabilities of exposure and 1.2, 1.2, and 1.1 for subjects with low, medium, and high intensity of exposure, respectively. The findings of this study did not suggest that industrial or occupational exposure is a major contributor to the etiology of pancreatic cancer. Further study may be needed to confirm the positive association between formaldehyde exposure and pancreatic cancer. JF - American Journal of Industrial Medicine AU - Kernan, G J AU - Ji, B-T AU - Dosemeci, M AU - Silverman, D T AU - Balbus, J AU - Zahm, SH AD - National Cancer Institute, 6120 Executive Blvd., EPS 8120, Rockville, MD 20852, USA Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 260 EP - 270 VL - 36 IS - 2 SN - 0271-3586, 0271-3586 KW - man KW - USA KW - pancreatic carcinoma KW - Toxicology Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Mortality KW - Pancreatic carcinoma KW - Solvents KW - Formaldehyde KW - Cancer KW - Occupational exposure KW - X 24240:Miscellaneous KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17376792?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Occupational+risk+factors+for+pancreatic+cancer%3A+A+case-control+study+based+on+death+certificates+from+24+U.S.+states&rft.au=Kernan%2C+G+J%3BJi%2C+B-T%3BDosemeci%2C+M%3BSilverman%2C+D+T%3BBalbus%2C+J%3BZahm%2C+SH&rft.aulast=Kernan&rft.aufirst=G&rft.date=1999-08-01&rft.volume=36&rft.issue=2&rft.spage=260&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2F%28SICI%291097-0274%28199908%2936%3A23.3.CO%3B2-G LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Risk assessment; Occupational exposure; Solvents; Formaldehyde; Mortality; Cancer; Pancreatic carcinoma DO - http://dx.doi.org/10.1002/(SICI)1097-0274(199908)36:2<260::AID-AJIM5>3.3.CO;2-G ER - TY - JOUR T1 - OxyR and SoxRS Regulation of fur AN - 17368467; 4570001 AB - The cytotoxic effects of reactive oxygen species are largely mediated by iron. Hydrogen peroxide reacts with iron to form the extremely reactive and damaging hydroxyl radical via the Fenton reaction. Superoxide anion accelerates this reaction because the dismutation of superoxide leads to increased levels of hydrogen peroxide and because superoxide elevates the intracellular concentration of iron by attacking iron-sulfur proteins. We found that regulators of the Escherichia coli responses to oxidative stress, OxyR and SoxRS, activate the expression of Fur, the global repressor of ferric ion uptake. A transcript encoding Fur was induced by hydrogen peroxide in a wild-type strain but not in a Delta oxyR strain, and DNase I footprinting assays showed that OxyR binds to the fur promoter. In cells treated with the superoxide-generating compound paraquat, we observed the induction of a longer transcript encompassing both fur and its immediate upstream gene fldA, which encodes a flavodoxin. This polycistronic mRNA is induced by paraquat in a wild-type strain but not in a Delta soxRS strain, and SoxS was shown to bind to the fldA promoter. These results demonstrate that iron metabolism is coordinately regulated with the oxidative stress defenses. JF - Journal of Bacteriology AU - Zheng, M AU - Doan, B AU - Schneider, T D AU - Storz, G AD - NIH, Building 18T, Room 101, 18 Library Dr., MSC 5430, Bethesda, MD 20892-5430., storz@helix.nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 4639 EP - 4643 VL - 181 IS - 15 SN - 0021-9193, 0021-9193 KW - Fur gene KW - Fur protein KW - OxyR protein KW - SoxRS protein KW - fldA gene KW - fldA protein KW - iron KW - superoxide KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Oxidative stress KW - Gene regulation KW - Iron KW - N 14930:Transcription factors KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17368467?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=OxyR+and+SoxRS+Regulation+of+fur&rft.au=Zheng%2C+M%3BDoan%2C+B%3BSchneider%2C+T+D%3BStorz%2C+G&rft.aulast=Zheng&rft.aufirst=M&rft.date=1999-08-01&rft.volume=181&rft.issue=15&rft.spage=4639&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Iron; Gene regulation; Oxidative stress ER - TY - JOUR T1 - Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer AN - 17366551; 4587165 AB - In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent (P-value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9-1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer. JF - British Journal of Cancer AU - Silverman, D T AU - Schiffman, M AU - Everhart, J AU - Goldstein, A AU - Lillemoe, K D AU - Swanson, G M AU - Schwartz, A G AU - Brown, L M AU - Greenberg, R S AU - Schoenberg, J B AU - Pottern, L M AU - Hoover, R N AU - Fraumeni, JF Jr AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South, Room 8108, Bethesda, MD, USA 20892-7240 Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 1830 EP - 1837 VL - 80 IS - 11 SN - 0007-0920, 0007-0920 KW - diabetes mellitus KW - family studies KW - pancreas KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Etiology KW - Allergies KW - Cancer KW - Genetics KW - Diseases KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17366551?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+Journal+of+Cancer&rft.atitle=Diabetes+mellitus%2C+other+medical+conditions+and+familial+history+of+cancer+as+risk+factors+for+pancreatic+cancer&rft.au=Silverman%2C+D+T%3BSchiffman%2C+M%3BEverhart%2C+J%3BGoldstein%2C+A%3BLillemoe%2C+K+D%3BSwanson%2C+G+M%3BSchwartz%2C+A+G%3BBrown%2C+L+M%3BGreenberg%2C+R+S%3BSchoenberg%2C+J+B%3BPottern%2C+L+M%3BHoover%2C+R+N%3BFraumeni%2C+JF+Jr&rft.aulast=Silverman&rft.aufirst=D&rft.date=1999-08-01&rft.volume=80&rft.issue=11&rft.spage=1830&rft.isbn=&rft.btitle=&rft.title=British+Journal+of+Cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer; Etiology; Allergies; Diseases; Genetics; Risk assessment ER - TY - JOUR T1 - The Structure of Multiple Polypeptide Domains Determines the Signal Recognition Particle Targeting Requirement of Escherichia coli Inner Membrane Proteins AN - 17360749; 4570013 AB - The signal recognition particle (SRP) targeting pathway is required for the efficient insertion of many polytopic inner membrane proteins (IMPs) into the Escherichia coli inner membrane, but in the absence of SRP protein export proceeds normally. To define the properties of IMPs that impose SRP dependence, we analyzed the targeting requirements of bitopic IMPs that are structurally intermediate between exported proteins and polytopic IMPs. We found that disruption of the SRP pathway inhibited the insertion of only a subset of bitopic IMPs. Studies on a model bitopic AcrB-alkaline phosphatase fusion protein (AcrB 265-AP) showed that the SRP requirement for efficient insertion correlated with the presence of a large periplasmic domain (P1). As previously reported, perturbation of the SRP pathway also affected the insertion of a polytopic AcrB-AP fusion. Even exhaustive SRP depletion, however, failed to block the insertion of any AcrB derivative by more than 50%. Taken together these data suggest that many proteins that are normally targeted by SRP can utilize alternative targeting pathways and that the structure of both hydrophilic and membrane-spanning domains determines the degree to which the biogenesis of a protein is SRP dependent. JF - Journal of Bacteriology AU - Newitt, JA AU - Ulbrandt, N D AU - Bernstein, H D AD - National Institutes of Health, Bldg. 10, Rm. 9D-20, Bethesda, MD 20892-1810, harris_bernstein@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 4561 EP - 4567 VL - 181 IS - 15 SN - 0021-9193, 0021-9193 KW - signal recognition particle KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Inner membranes KW - Escherichia coli KW - Membrane proteins KW - N 14910:Nucleoproteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17360749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+Structure+of+Multiple+Polypeptide+Domains+Determines+the+Signal+Recognition+Particle+Targeting+Requirement+of+Escherichia+coli+Inner+Membrane+Proteins&rft.au=Newitt%2C+JA%3BUlbrandt%2C+N+D%3BBernstein%2C+H+D&rft.aulast=Newitt&rft.aufirst=JA&rft.date=1999-08-01&rft.volume=181&rft.issue=15&rft.spage=4561&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Membrane proteins; Inner membranes ER - TY - JOUR T1 - Protein Kinase A-RI alpha Antisense: Antitumor Mechanism of Action AN - 17346355; 4606514 AB - Cancer cells are characterized by arrest at an incomplete stage of maturation while retaining their capacity to proliferate. Recently, researchers have begun clinical trials of several agents that act by changing the biologic properties of cancer cells so that they lose the ability to divide continuously. Once this occurs, the cells are programmed to die. Understanding the molecular mechanisms underlying the signal transduction pathways in higher organisms is crucial in addressing such long-standing questions in cell biology as what causes cells to begin and to stop dividing and how many disturbances in those growth control mechanisms give rise to cancer. Antisense oligodeoxynucleotides (ODN) are short synthetic nucleotide sequences complementary to a specific gene or RNA message. Through the binding of these oligomers to a target DNA or mRNA sequence, transcription or translation of a gene can be selectively blocked, and the disease process generated by that gene can be halted. The antisense target herein described is cyclic AMP (CAMP)-dependent protein kinase type I (PKA-I). Changing the ratio of the two isoforms of the protein kinase A type I (PKA-I) and type II (PKA-II), which are distinguished by different regulatory subunits, RI and RII, has been linked to cell growth and differentiation. An enhanced expression of RI/PKA-I correlates with active cell growth and cell transformation, whereas a decrease in RI/PKA-I and an increase in RII/PKA-II are related to growth inhibition and differentiation maturation. The evidence presented shows that the sequence-specific inhibition of RI alpha gene expression by antisense oligonucleotides results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin and sustained inhibition of tumor growth in athymic mice. The loss of RI alpha by the antisense results in rapid increase in the half-life of RII beta protein via its stabilization in a holoenzyme complex (PKA-II). This compensatory stabilization of RII beta protein may represent a novel biochemical mechanism of RI alpha antisense that ensures depletion of PKA-I and sustained inhibition of tumor growth. JF - Antisense and Nucleic Acid Drug Development AU - Cho-Chung, Yoon S AU - Nesterova, M AU - Park, Y G AU - Lee, Youl Nam AD - National Cancer Institute, Building 10, room 5B05, Bethesda, MD 20892-1750, USA Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 383 EP - 388 VL - 9 IS - 4 SN - 1087-2906, 1087-2906 KW - mice KW - oligodeoxyribonucleotides KW - oligonucleotides KW - protein kinase A KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Cyclic AMP KW - Antitumor agents KW - Carcinoma KW - Leukemia KW - Antisense KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews KW - W3 33380:Antisense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17346355?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Protein+Kinase+A-RI+alpha+Antisense%3A+Antitumor+Mechanism+of+Action&rft.au=Cho-Chung%2C+Yoon+S%3BNesterova%2C+M%3BPark%2C+Y+G%3BLee%2C+Youl+Nam&rft.aulast=Cho-Chung&rft.aufirst=Yoon&rft.date=1999-08-01&rft.volume=9&rft.issue=4&rft.spage=383&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinoma; Leukemia; Antitumor agents; Cyclic AMP; Antisense ER - TY - JOUR T1 - Oligonucleotides Containing 5,6-Dihydro-5-Azacytosine at CpG Sites Can Produce Potent Inhibition of DNA Cytosine-C5-Methyltransferase without Covalently Binding to the Enzyme AN - 17342812; 4606520 AB - C5-cytosine methylation of DNA at CpG sites is catalyzed by DNA cytosine- C5-methyltransferase (C5-MTase) in both prokaryotes and eukaryotes. The mechanism of transfer of the methyl group from the cofactor S- adenosyl-L-methionine (AdoMet) to the target cytosine occurs in a similar fashion in most (if not all) C5-MTases, which share highly conserved sequence motifs in the catalytic and AdoMet binding regions. In mammals, the enzyme is responsible for the maintenance of methylation patterns in the genome. However, aberrant DNA methylation patterns are associated with tumorigenesis and are common in cancer. JF - Antisense and Nucleic Acid Drug Development AU - Marquez, V E AU - Goddard, A AU - Alvarez, E AU - Ford, H Jr AU - Christman, J K AU - Sheikhnejad, G AU - Brank, A AU - Marasco, C J AU - Suffrin, J R AU - O'Gara, M AU - Cheng, X AD - Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, Building 37, Room 5C-02, 37 Convent Drive, MSC 4255, Bethesda, MD 20892-4255, USA Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 415 EP - 421 VL - 9 IS - 4 SN - 1087-2906, 1087-2906 KW - 5,6-dihydro-5-azacytosine KW - oligodeoxyribonucleotides KW - oligonucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - DNA (cytosine-5-)-methyltransferase KW - Tumors KW - DNA methylation KW - S-Adenosylmethionine KW - W3 33385:DNA/RNA KW - N 14250:Biological properties KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17342812?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antisense+and+Nucleic+Acid+Drug+Development&rft.atitle=Oligonucleotides+Containing+5%2C6-Dihydro-5-Azacytosine+at+CpG+Sites+Can+Produce+Potent+Inhibition+of+DNA+Cytosine-C5-Methyltransferase+without+Covalently+Binding+to+the+Enzyme&rft.au=Marquez%2C+V+E%3BGoddard%2C+A%3BAlvarez%2C+E%3BFord%2C+H+Jr%3BChristman%2C+J+K%3BSheikhnejad%2C+G%3BBrank%2C+A%3BMarasco%2C+C+J%3BSuffrin%2C+J+R%3BO%27Gara%2C+M%3BCheng%2C+X&rft.aulast=Marquez&rft.aufirst=V&rft.date=1999-08-01&rft.volume=9&rft.issue=4&rft.spage=415&rft.isbn=&rft.btitle=&rft.title=Antisense+and+Nucleic+Acid+Drug+Development&rft.issn=10872906&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - DNA (cytosine-5-)-methyltransferase; DNA methylation; S-Adenosylmethionine; Tumors ER - TY - JOUR T1 - Identification and characterization of a Chlamydia trachomatis early operon encoding four novel inclusion membrane proteins AN - 17321987; 4599854 AB - Chlamydia trachomatis is a bacterial obligate intracellular parasite that replicates within a vacuole, termed an inclusion, that does not fuse with lysosomes. Within 2 h after internalization, the C. trachomatis inclusion ceases to interact with the endocytic pathway and, instead, becomes fusogenic with exocytic vesicles containing exogenously synthesized NBD-sphingomyelin. Both fusion of exocytic vesicles and long-term avoidance of lysosomal fusion require early chlamydial gene expression. Modification of the chlamydial inclusion probably occurs through the expression and insertion of chlamydial protein(s) into the inclusion membrane. To identify candidate inclusion membrane proteins, antisera were raised against a total membrane fraction purified from C. trachomatis-infected HeLa cells. By indirect immunofluorescence, this antisera recognized the inclusion membrane and, by immunoblot analysis, recognized three chlamydial-specific antigens of approximate molecular weights 15, 18 and 21 kDa. IncG, encoding an 18 kDa and 21 kDa doublet chlamydial antigen, was identified by screening a C. trachomatis, serovar L2, genomic expression library. Three additional genes, incD, incE and incF, were co-transcribed with incG. Monospecific antisera against each of the four genes of this operon demonstrated that the gene products were localized to the chlamydial inclusion membrane. Immediately downstream from the operon containing incD-G was the C. trachomatis homologue of incA. Like IncD, E, F and G, C. trachomatis Inca is also localized to the inclusion membrane. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that IncD-G, but not incA, are transcribed within the first 2 h after internalization, making them candidates for chlamydial factors required for the modification of the nascent chlamydial inclusion. JF - Molecular Microbiology AU - Scidmore-Carlson, MA AU - Shaw, E I AU - Dooley, CA AU - Fischer, E R AU - Hackstadt, T AD - Host-Parasite Interactions Section, Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, MT 59840, USA, Ted_Hackstadt@NIH.GOV Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 753 EP - 765 VL - 33 IS - 4 SN - 0950-382X, 0950-382X KW - IncA protein KW - IncD protein KW - IncE protein KW - IncF protein KW - IncG protein KW - amino acid sequence prediction KW - cDNA KW - incA gene KW - incD gene KW - incE gene KW - incF gene KW - incG gene KW - nucleotide sequence KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Chlamydia trachomatis KW - Membrane proteins KW - N 14640:Structure & sequence KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17321987?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Identification+and+characterization+of+a+Chlamydia+trachomatis+early+operon+encoding+four+novel+inclusion+membrane+proteins&rft.au=Scidmore-Carlson%2C+MA%3BShaw%2C+E+I%3BDooley%2C+CA%3BFischer%2C+E+R%3BHackstadt%2C+T&rft.aulast=Scidmore-Carlson&rft.aufirst=MA&rft.date=1999-08-01&rft.volume=33&rft.issue=4&rft.spage=753&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Membrane proteins ER - TY - JOUR T1 - Cloning and Analysis of the rnc-era-recO Operon from Pseudomonas aeruginosa AN - 17318235; 4576397 AB - The rnc operon from Pseudomonas aeruginosa has been cloned and characterized. The three genes comprising this operon, rnc, era, and recO, are arranged similarly to those in some other gram- negative bacteria. Multicopy plasmids carrying the rnc operon of P. aeruginosa functionally complement mutations of the rnc, era, and recO genes in Escherichia coli. In particular, the P. aeruginosa era homolog rescues the conditional lethality of era mutants in E. coli, and the presumptive protein has 60% identity with the Era of E. coli. We discuss these data and evidence suggesting that a GTPase previously purified from P. aeruginosa and designated Pra is not an Era homolog. JF - Journal of Bacteriology AU - Powell, B AU - Peters, HK III AU - Nakamura, Y AU - Court, D AD - Gene Regulation and Chromosome Biology Laboratory, ABL---Basic Research Program NCI---Frederick Cancer Research and Development Center, P.O. Box B Frederick, MD 21702-1201, court@ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 5111 EP - 5113 VL - 181 IS - 16 SN - 0021-9193, 0021-9193 KW - amino acid sequence prediction KW - cDNA KW - era gene KW - nucleotide sequence KW - recO gene KW - rnc gene KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Lethality KW - Escherichia coli KW - Pseudomonas aeruginosa KW - Guanosinetriphosphatase KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17318235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Cloning+and+Analysis+of+the+rnc-era-recO+Operon+from+Pseudomonas+aeruginosa&rft.au=Powell%2C+B%3BPeters%2C+HK+III%3BNakamura%2C+Y%3BCourt%2C+D&rft.aulast=Powell&rft.aufirst=B&rft.date=1999-08-01&rft.volume=181&rft.issue=16&rft.spage=5111&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Pseudomonas aeruginosa; Guanosinetriphosphatase; Lethality ER - TY - JOUR T1 - Impact of Cytokine Administration on the Generation of Antitumor Reactivity in Patients with Metastatic Melanoma Receiving a Peptide Vaccine AN - 17317051; 4585936 AB - Patients with metastatic melanoma were immunized with an immunodominant peptide derived from the gp100 melanoma-melanocyte differentiation Ag that was modified to increase binding to HLA-A super(+)0201. A total of 10 of 11 patients who received the g209-2M peptide alone developed precursors reactive with the native g209 peptide, compared with only 5 of 16 patients who received g209-2M peptide plus IL-2 (p sub(2) = 0.005). Peptide reactivity closely correlated with the recognition of HLA-A super(+)0201 melanoma cells (p < 0.001). The decrease in immune reactivity when peptide was administered with IL-2 appeared specific for the immunizing peptide, since reactivity to an influenza peptide resulting from prior exposure was not affected. Preexisting antitumor precursors did not decrease when peptide plus IL-2 was administered. The administration of GM-CSF or IL-12 also resulted in a decrease in circulating precursors compared with the administration of peptide alone, though not as great a decrease as that seen with IL-2. Immunization with peptide plus IL-2 did, however, appear to have clinical impact since 6 of the 16 patients (38%) that received peptide plus IL-2 had objective cancer regressions. It thus appeared possible that immunization with peptide plus IL-2 resulted in sequestering or apoptotic destruction of newly activated immune cells at the tumor site. These represent the first detailed studies of the impact of immunization with tumor peptides in conjunction with a variety of cytokines in patients with metastatic cancer. JF - Journal of Immunology AU - Rosenberg, SA AU - Yang, J C AU - Schwartzentruber, D J AU - Hwu, P AU - Marincola, F M AU - Topalian, S L AU - Restifo, N P AU - Sznol, M AU - Schwarz, S L AU - Spiess, P J AU - Wunderlich, J R AU - Seipp, CA AU - Einhorn, J H AU - Rogers-Freezer, L AU - White, DE AD - National Cancer Institute, 9000 Rockville Pike, Building 10, Room 2B42, Bethesda, MD 20892, USA, SAR@nih.gov Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 1690 EP - 1695 VL - 163 IS - 3 SN - 0022-1767, 0022-1767 KW - cancer vaccines KW - immunology KW - man KW - peptide vaccines KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antigen (tumor-associated) KW - Vaccines KW - Melanoma KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17317051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Impact+of+Cytokine+Administration+on+the+Generation+of+Antitumor+Reactivity+in+Patients+with+Metastatic+Melanoma+Receiving+a+Peptide+Vaccine&rft.au=Rosenberg%2C+SA%3BYang%2C+J+C%3BSchwartzentruber%2C+D+J%3BHwu%2C+P%3BMarincola%2C+F+M%3BTopalian%2C+S+L%3BRestifo%2C+N+P%3BSznol%2C+M%3BSchwarz%2C+S+L%3BSpiess%2C+P+J%3BWunderlich%2C+J+R%3BSeipp%2C+CA%3BEinhorn%2C+J+H%3BRogers-Freezer%2C+L%3BWhite%2C+DE&rft.aulast=Rosenberg&rft.aufirst=SA&rft.date=1999-08-01&rft.volume=163&rft.issue=3&rft.spage=1690&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Antigen (tumor-associated); Vaccines ER - TY - JOUR T1 - Infection of HIV-1 Transgenic Mice with Mycobacterium avium Induces the Expression of Infectious Virus Selectively from a Mac-1-Positive Host Cell Population AN - 17316843; 4585913 AB - Infection of HIV-1-transgenic mice with Mycobacterium avium, a common opportunistic pathogen in AIDS patients, was shown to result in increased tissue expression of viral specific transcripts. Moreover, by coculturing splenocytes from the transgenic animals with human T cells it was possible to demonstrate that the elevation in HIV-1 mRNA triggered by M. avium infection reflects increased production of infectious virions. Viral immune activation was also shown to correlate with a marked elevation of p24 in supernatants of ex vivo-cultured tissues and, more importantly, in systemic increases in the HIV-1 protein in plasma. Interestingly, these tissue and systemic p24 responses were found to be differentially regulated. Thus, while in vitro p24 production by cultured splenocytes increased concurrently with bacterial loads during the first 6 wk of infection, levels of the Ag in plasma actually decreased. In situ localization experiments together with FACS analysis of HIV-1-expressing splenocytes indicated that virus production is restricted largely to cells of the monocyte/macrophage lineage. Indeed, in vitro p24 expression by cells from noninfected transgenic mice was up-regulated by polyclonal stimulation of macrophages but not T cells. Together these results underscore the importance of the macrophage reservoir in persistent virus expression and establish a convenient and relevant animal model for studying the factors responsible for immune activation of HIV-1 induced by mycobacterial as well as other common coinfections encountered by AIDS patients. JF - Journal of Immunology AU - Doherty, T M AU - Chougnet, C AU - Schito, M AU - Patterson, B K AU - Fox, C AU - Shearer, G M AU - Englund, G AU - Sher, A AD - Building 4, Room 126, National Institutes of Health, 4 Center Drive, Bethesda, MD 20892-0425, USA, alan_sher@nih.gov Y1 - 1999/08/01/ PY - 1999 DA - 1999 Aug 01 SP - 1506 EP - 1515 VL - 163 IS - 3 SN - 0022-1767, 0022-1767 KW - HIV-1 KW - Human immunodeficiency virus 1 KW - Mac-1 antigen KW - Mycobacterium avium KW - immunology KW - p24 protein KW - transgenic mice KW - Virology & AIDS Abstracts; Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Macrophages KW - Acquired immune deficiency syndrome KW - Animal models KW - Opportunist infection KW - Splenocytes KW - Immunocompromised hosts KW - F 06880:Gastrointestinal tract & liver KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms KW - V 22003:AIDS: Immunological aspects KW - F 06860:CMI UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17316843?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Infection+of+HIV-1+Transgenic+Mice+with+Mycobacterium+avium+Induces+the+Expression+of+Infectious+Virus+Selectively+from+a+Mac-1-Positive+Host+Cell+Population&rft.au=Doherty%2C+T+M%3BChougnet%2C+C%3BSchito%2C+M%3BPatterson%2C+B+K%3BFox%2C+C%3BShearer%2C+G+M%3BEnglund%2C+G%3BSher%2C+A&rft.aulast=Doherty&rft.aufirst=T&rft.date=1999-08-01&rft.volume=163&rft.issue=3&rft.spage=1506&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Mycobacterium avium; Opportunist infection; Acquired immune deficiency syndrome; Immunocompromised hosts; Splenocytes; Macrophages; Animal models ER - TY - JOUR T1 - An uncommon Helicobacter isolate from blood: Evidence of a group of Helicobacter spp. pathogenic in AIDS patients AN - 17273293; 4588089 AB - An unusual Helicobacter sp. was isolated from the blood of a human immunodeficiency virus (HIV)-infected patient. This organism had spiral morphology, with single amphitrichous flagella, and was negative for hippurate hydrolysis, production of urease, and reduction of nitrate. 16S rRNA gene sequence analysis verified that the isolate was a species of Helicobacter, most closely related to an undescribed Helicobacter-like isolate from Vancouver, British Columbia, Canada, and to Helicobacter westmeadii, a recently described species from Australia. Both organisms had also been isolated from the blood of HIV-infected patients. These blood isolates, along with Helicobacter cinaedi, form a cluster of closely related Helicobacter spp. that may represent an emerging group of pathogens in immunocompromised patients. JF - Journal of Clinical Microbiology AU - Weir, S C AU - Gibert, CL AU - Gordin, F M AU - Fischer, SH AU - Gill, V J AD - Microbiology Service, Clinical Pathology Department, Building 10, Room 2C-385, 9000 Rockville Pike, Bethesda, MD 20892, USA, vgill@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 2729 EP - 2733 VL - 37 IS - 8 SN - 0095-1137, 0095-1137 KW - Australia KW - Canada KW - Canada, British Columbia, Vancouver KW - Hippuric acid KW - Nitrate KW - USA KW - USA, Northeast KW - rRNA 16S KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology KW - Phylogeny KW - Acquired immune deficiency syndrome KW - Helicobacter KW - Genotyping KW - Urease KW - Helicobacter cinaedi KW - Blood KW - Helicobacter westmeadii KW - Immunocompromised hosts KW - Human immunodeficiency virus 1 KW - Flagella KW - J 02710:Identification, taxonomy and typing KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17273293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=An+uncommon+Helicobacter+isolate+from+blood%3A+Evidence+of+a+group+of+Helicobacter+spp.+pathogenic+in+AIDS+patients&rft.au=Weir%2C+S+C%3BGibert%2C+CL%3BGordin%2C+F+M%3BFischer%2C+SH%3BGill%2C+V+J&rft.aulast=Weir&rft.aufirst=S&rft.date=1999-08-01&rft.volume=37&rft.issue=8&rft.spage=2729&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter; Helicobacter cinaedi; Helicobacter westmeadii; Human immunodeficiency virus 1; Urease; Phylogeny; Genotyping; Acquired immune deficiency syndrome; Immunocompromised hosts; Flagella; Blood ER - TY - JOUR T1 - Heteroresistance to fluconazole and voriconazole in Cryptococcus neoformans AN - 17268393; 4587982 AB - Cryptococcus neoformans isolates that exhibited unusual patterns of resistance to fluconazole and voriconazole were isolated from seven isolates from two different geographical regions: one isolate from an Israeli non-AIDS patient and six serial isolates from an Italian AIDS patient who had suffered six recurrent episodes of cryptococcal meningitis. Each isolate produced cultures with heterogeneous compositions in which most of the cells were susceptible, but cells highly resistant to fluconazole (MICs, greater than or equal to 64 mu g/ml) were recovered at a variable frequency (7 times 10 super(-3) to 4.6 times 10 super(-2)). Evidence showed that this type of resistance is innate and is unrelated to drug exposure since the Israeli patient had never been treated with azoles or any other antimycotic agents. Analysis of clonal subpopulations of these two strains showed that they exhibited heterogeneous patterns of resistance. The number of subpopulations which grew on fluconazole or voriconazole agar declined progressively with increasing azole concentration without a sharp cutoff point. For the Italian serial isolates, the number of clonal populations resistant to fluconazole (64 mu g/ml) and voriconazole (1 mu g/ml) increased steadily, yielding the highest number for the isolate from the last episode. Attempts to purify a sensitive subpopulation failed, but clones highly resistant to fluconazole (100 mu g/ml) and moderately resistant to voriconazole (1 mu g/ml) always produced a homogeneous population of resistant cells. Upon maintenance on drug-free medium, however, the majority of the homogeneously resistant cells of these subclones lost their resistance and returned to the stable initial heteroresistant phenotype. The pattern of heteroresistance was not affected by the pH or osmolarity of the medium but was influenced by temperature. The resistance appeared to be suppressed at 35 degree C and was completely abolished at 40 degree C. Although heterogeneity in azole resistance among subpopulations of single isolates has been reported for Candida species, the transient changes in expression of resistance under different growth conditions reported here have not been observed in fungal pathogens. JF - Antimicrobial Agents & Chemotherapy AU - Mondon, P AU - Petter, R AU - Amalfitano, G AU - Luzzati, R AU - Concia, E AU - Polacheck, I AU - Kwon-Chung, K J AD - MMS, LCI, NIAID, Bldg. 10, 11C304, National Institutes of Health, Bethesda, MD 20892, USA, June_Kwon-chung@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 1856 EP - 1861 VL - 43 IS - 8 SN - 0066-4804, 0066-4804 KW - Voriconazole KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Fluconazole KW - Temperature effects KW - Antifungal agents KW - Drug resistance KW - Candida KW - Minimum inhibitory concentration KW - Cryptococcus neoformans KW - Media (culture) KW - A 01064:Microbial resistance KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17268393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Heteroresistance+to+fluconazole+and+voriconazole+in+Cryptococcus+neoformans&rft.au=Mondon%2C+P%3BPetter%2C+R%3BAmalfitano%2C+G%3BLuzzati%2C+R%3BConcia%2C+E%3BPolacheck%2C+I%3BKwon-Chung%2C+K+J&rft.aulast=Mondon&rft.aufirst=P&rft.date=1999-08-01&rft.volume=43&rft.issue=8&rft.spage=1856&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Candida; Cryptococcus neoformans; Media (culture); Temperature effects; Drug resistance; Minimum inhibitory concentration; Antifungal agents; Fluconazole ER - TY - JOUR T1 - Recurrent bacteremia caused by a 'Flexispira'-like organism in a patient with X-linked (Bruton's) agammaglobulinemia AN - 17268243; 4588036 AB - Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H sub(2) for growth. Optimal growth was observed at 35 to 37 degree C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name 'Flexispira rappini' by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to 'F. rappini' and even less to other Helicobacter spp. Although the organism phenotypically resembles 'Flexispira' and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin. JF - Journal of Clinical Microbiology AU - Weir, S AU - Cuccherini, B AU - Whitney, A M AU - Ray, M L AU - MacGregor, J P AU - Steigerwalt, A AU - Daneshvar, MI AU - Weyant, R AU - Wray, B AU - Steele, J AU - Strober, W AU - Gill, V J AD - Microbiology Service, Bldg. 10/Rm2C-385, Department of Clinical Pathology, W.G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA, vjgill@nih.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 2439 EP - 2445 VL - 37 IS - 8 SN - 0095-1137, 0095-1137 KW - agammaglobulinemia KW - rRNA 16S gene KW - Microbiology Abstracts B: Bacteriology KW - Culture KW - Helicobacter KW - Genotyping KW - Flexispira KW - Bacteremia KW - Urease KW - Taxonomy KW - Hybridization analysis KW - J 02710:Identification, taxonomy and typing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17268243?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Recurrent+bacteremia+caused+by+a+%27Flexispira%27-like+organism+in+a+patient+with+X-linked+%28Bruton%27s%29+agammaglobulinemia&rft.au=Weir%2C+S%3BCuccherini%2C+B%3BWhitney%2C+A+M%3BRay%2C+M+L%3BMacGregor%2C+J+P%3BSteigerwalt%2C+A%3BDaneshvar%2C+MI%3BWeyant%2C+R%3BWray%2C+B%3BSteele%2C+J%3BStrober%2C+W%3BGill%2C+V+J&rft.aulast=Weir&rft.aufirst=S&rft.date=1999-08-01&rft.volume=37&rft.issue=8&rft.spage=2439&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Flexispira; Helicobacter; Urease; Hybridization analysis; Culture; Bacteremia; Taxonomy; Genotyping ER - TY - JOUR T1 - Ecology of the Patagonia puma Felis concolor patagonica in southern Chile AN - 17258699; 4547532 AB - The ecology of the Patagonia puma was studied in Torres del Paine National Park, Chile. Thirteen pumas were captured from 1986 to 1989 and equipped with radio transmitters. During the winter of 1988 there was one puma per 17 km super(2) in the 200 km super(2) study area. Home ranges varied from 24 to 107 km super(2). Female home ranges overlapped with those of other males and females extensively, but male ranges overlapped each other for only short time periods. Seven adult pumas had home ranges extending outside the park boundaries and at least three preyed on sheep. Guanacos Lama guanicoe, especially young animals, were the puma's most important prey item by biomass, but European hares Lepus capensis were preyed upon more than expected relative to available biomass. Of 731 guanaco skulls collected from 1979 to 1988, 33% showed clear evidence of having been killed by pumas. Over the past decade puma numbers are believed to have increased in the park, perhaps in response to an increase in guanaco numbers and continued protection. With decreased hunting pressure and harassment by horses and dogs, pumas have habituated to people and are being observed more often by park visitors. JF - Biological Conservation AU - Franklin, W L AU - Johnson, W E AU - Sarno, R J AU - Iriarte, JA AD - Laboratory of Genomic Diversity National Cancer Institute Frederick, MD 21702-1201, USA, johnsonw@ncifcrf.gov Y1 - 1999/08// PY - 1999 DA - Aug 1999 SP - 33 EP - 40 VL - 90 IS - 1 SN - 0006-3207, 0006-3207 KW - Chile KW - Mountain lion KW - Ecology Abstracts KW - Diets KW - Felis concolor KW - Telemetry KW - Population density KW - Home range KW - Radio-tagging KW - D 04672:Mammals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17258699?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+Conservation&rft.atitle=Ecology+of+the+Patagonia+puma+Felis+concolor+patagonica+in+southern+Chile&rft.au=Franklin%2C+W+L%3BJohnson%2C+W+E%3BSarno%2C+R+J%3BIriarte%2C+JA&rft.aulast=Franklin&rft.aufirst=W&rft.date=1999-08-01&rft.volume=90&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Biological+Conservation&rft.issn=00063207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Felis concolor; Population density; Diets; Telemetry; Radio-tagging; Home range ER - TY - JOUR T1 - Comparison of the roles of the C1a and C1b domains of protein kinase C alpha in ligand induced translocation in NIH 3T3 cells. AN - 69975874; 10452523 AB - To explore the relative roles of the two C1 domains of protein kinase C alpha (PKC alpha) in the response to phorbol esters and related analogs, we mutated the individual C1 domains, expressed the mutated PKC alpha in NIH 3T3 cells, and then examined the ability of ligands to induce its translocation to the membrane. The C1a and C1b domains play equivalent roles for translocation in response to phorbol 12-myristate 13-acetate, mezerein, and (-)octylindolactam V. These results contrast with those previously reported for PKC delta, suggesting that the domains play different roles in different PKC isoforms. JF - FEBS letters AU - Bögi, K AU - Lorenzo, P S AU - Acs, P AU - Szállási, Z AU - Wagner, G S AU - Blumberg, P M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1999/07/30/ PY - 1999 DA - 1999 Jul 30 SP - 27 EP - 30 VL - 456 IS - 1 SN - 0014-5793, 0014-5793 KW - Diterpenes KW - 0 KW - Indoles KW - Isoenzymes KW - Lactams KW - Terpenes KW - 7-octylindolactam V KW - 109346-66-9 KW - mezerein KW - 34807-41-5 KW - Prkca protein, mouse KW - EC 2.7.11.13 KW - Protein Kinase C KW - Protein Kinase C-alpha KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Membrane -- enzymology KW - Cells, Cultured -- drug effects KW - Mice KW - Lactams -- pharmacology KW - Structure-Activity Relationship KW - Biological Transport -- drug effects KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Indoles -- pharmacology KW - Terpenes -- pharmacology KW - Cells, Cultured -- enzymology KW - Mutation KW - Protein Kinase C -- metabolism KW - Isoenzymes -- chemistry KW - Translocation, Genetic -- genetics KW - Protein Kinase C -- drug effects KW - 3T3 Cells -- drug effects KW - Protein Kinase C -- genetics KW - Protein Kinase C -- chemistry KW - Isoenzymes -- drug effects KW - Isoenzymes -- genetics KW - 3T3 Cells -- enzymology KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69975874?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=Comparison+of+the+roles+of+the+C1a+and+C1b+domains+of+protein+kinase+C+alpha+in+ligand+induced+translocation+in+NIH+3T3+cells.&rft.au=B%C3%B6gi%2C+K%3BLorenzo%2C+P+S%3BAcs%2C+P%3BSz%C3%A1ll%C3%A1si%2C+Z%3BWagner%2C+G+S%3BBlumberg%2C+P+M&rft.aulast=B%C3%B6gi&rft.aufirst=K&rft.date=1999-07-30&rft.volume=456&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - G(i) protein-mediated functional compartmentalization of cardiac beta(2)-adrenergic signaling. AN - 69911160; 10419531 AB - In contrast to beta(1)-adrenoreceptor (beta(1)-AR) signaling, beta(2)-AR stimulation in cardiomyocytes augments L-type Ca(2+) current in a cAMP-dependent protein kinase (PKA)-dependent manner but fails to phosphorylate phospholamban, indicating that the beta(2)-AR-induced cAMP/PKA signaling is highly localized. Here we show that inhibition of G(i) proteins with pertussis toxin (PTX) permits a full phospholamban phosphorylation and a de novo relaxant effect following beta(2)-AR stimulation, converting the localized beta(2)-AR signaling to a global signaling mode similar to that of beta(1)-AR. Thus, beta(2)-AR-mediated G(i) activation constricts the cAMP signaling to the sarcolemma. PTX treatment did not significantly affect the beta(2)-AR-stimulated PKA activation. Similar to G(i) inhibition, a protein phosphatase inhibitor, calyculin A (3 x 10(-8) M), selectively enhanced the beta(2)-AR but not beta(1)-AR-mediated contractile response. Furthermore, PTX and calyculin A treatment had a non-additive potentiating effect on the beta(2)-AR-mediated positive inotropic response. These results suggest that the interaction of the beta(2)-AR-coupled G(i) and G(s) signaling affects the local balance of protein kinase and phosphatase activities. Thus, the additional coupling of beta(2)-AR to G(i) proteins is a key factor causing the compartmentalization of beta(2)-AR-induced cAMP signaling. JF - The Journal of biological chemistry AU - Kuschel, M AU - Zhou, Y Y AU - Cheng, H AU - Zhang, S J AU - Chen, Y AU - Lakatta, E G AU - Xiao, R P AD - Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA. Y1 - 1999/07/30/ PY - 1999 DA - 1999 Jul 30 SP - 22048 EP - 22052 VL - 274 IS - 31 SN - 0021-9258, 0021-9258 KW - Adrenergic beta-2 Receptor Agonists KW - 0 KW - Adrenergic beta-2 Receptor Antagonists KW - Calcium Channels KW - Calcium Channels, L-Type KW - Calcium-Binding Proteins KW - Ethanolamines KW - Oxazoles KW - Propanolamines KW - Receptors, Adrenergic, beta-2 KW - Thionucleotides KW - Vasoconstrictor Agents KW - Virulence Factors, Bordetella KW - phospholamban KW - adenosine-3',5'-cyclic phosphorothioate KW - 23645-17-2 KW - ICI 118551 KW - 46OL1UC10R KW - zinterol KW - 7167N7AJJR KW - calyculin A KW - 7D07U14TK3 KW - Cyclic AMP KW - E0399OZS9N KW - Pertussis Toxin KW - EC 2.4.2.31 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - GTP-Binding Protein alpha Subunits, Gi-Go KW - EC 3.6.5.1 KW - Index Medicus KW - Cyclic AMP-Dependent Protein Kinases -- metabolism KW - Animals KW - Vasoconstrictor Agents -- pharmacology KW - Calcium Channels -- physiology KW - Cell Size KW - Cyclic AMP -- analogs & derivatives KW - Myocardial Contraction -- drug effects KW - Rats KW - Virulence Factors, Bordetella -- pharmacology KW - Thionucleotides -- pharmacology KW - Phosphorylation KW - Oxazoles -- pharmacology KW - Cyclic AMP -- pharmacology KW - Myocardial Contraction -- physiology KW - Calcium-Binding Proteins -- metabolism KW - Propanolamines -- pharmacology KW - Heart Ventricles KW - GTP-Binding Protein alpha Subunits, Gi-Go -- physiology KW - Signal Transduction -- physiology KW - Myocardium -- cytology KW - Ethanolamines -- pharmacology KW - Receptors, Adrenergic, beta-2 -- physiology KW - Signal Transduction -- drug effects KW - Heart -- physiology KW - Heart -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69911160?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=G%28i%29+protein-mediated+functional+compartmentalization+of+cardiac+beta%282%29-adrenergic+signaling.&rft.au=Kuschel%2C+M%3BZhou%2C+Y+Y%3BCheng%2C+H%3BZhang%2C+S+J%3BChen%2C+Y%3BLakatta%2C+E+G%3BXiao%2C+R+P&rft.aulast=Kuschel&rft.aufirst=M&rft.date=1999-07-30&rft.volume=274&rft.issue=31&rft.spage=22048&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification by chimera formation and site-selected mutagenesis of a key amino acid residue involved in determining stereospecificity of guinea pig 3-hydroxysteroid sulfotransferase isoforms. AN - 69909384; 10419461 AB - The 3-hydroxysteroid sulfotransferases that have been isolated and cloned from humans and rodents appear to have broad substrate specificities. In the guinea pig, however, two 3-hydroxysteroid sulfotransferases have been isolated that function according to an innate stereospecificity: the alpha-isoform acts on steroids with a 3-hydroxyl group oriented in the alpha position, whereas the beta-isoform acts on steroids where the 3-hydroxyl group is in a beta orientation. To examine the structural basis for this remarkable stereoselectivity, chimeras of the two enzymes, which are 87% identical, were constructed. A chimera consisting of the NH(2)-terminal 91 amino acids of the alpha-isoform and the COOH-terminal 196 amino acids of the beta-isoform displayed activity similar to that of the alpha-isoform. Site-selected mutagenesis of this 3alpha/beta-hydroxysteroid sulfotransferase chimera involving the 12 amino acid differences that exist between the two isoforms within the 91 amino acid NH(2)-terminal region revealed that the amino acid residue at position 51 plays a fundamental role in determining the stereospecificity exhibited by the alpha- and beta-isoforms, i.e. if residue 51 is an asparagine, alpha activity predominates, whereas if an isoleucine is in that position, beta activity prevails. JF - The Journal of biological chemistry AU - Park, B C AU - Lee, Y C AU - Strott, C A AD - Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 1999/07/30/ PY - 1999 DA - 1999 Jul 30 SP - 21562 EP - 21568 VL - 274 IS - 31 SN - 0021-9258, 0021-9258 KW - DNA Primers KW - 0 KW - Isoenzymes KW - Recombinant Fusion Proteins KW - Pregnenolone KW - 73R90F7MQ8 KW - Androsterone KW - C24W7J5D5R KW - Sulfotransferases KW - EC 2.8.2.- KW - alcohol sulfotransferase KW - EC 2.8.2.2 KW - Index Medicus KW - Isoenzymes -- chemistry KW - Animals KW - Stereoisomerism KW - Androsterone -- metabolism KW - Guinea Pigs KW - Amino Acid Sequence KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Sequence Alignment KW - Pregnenolone -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Substrate Specificity KW - Sequence Homology, Amino Acid KW - Amino Acid Substitution KW - Sulfotransferases -- genetics KW - Sulfotransferases -- metabolism KW - Sulfotransferases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69909384?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+by+chimera+formation+and+site-selected+mutagenesis+of+a+key+amino+acid+residue+involved+in+determining+stereospecificity+of+guinea+pig+3-hydroxysteroid+sulfotransferase+isoforms.&rft.au=Park%2C+B+C%3BLee%2C+Y+C%3BStrott%2C+C+A&rft.aulast=Park&rft.aufirst=B&rft.date=1999-07-30&rft.volume=274&rft.issue=31&rft.spage=21562&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Decreased expression of CD80 is a marker for increased tumorigenicity in a new murine model of oral squamous-cell carcinoma. AN - 69878149; 10399955 AB - We established a new syngeneic murine model of oral squamous-cell carcinoma (SCC) to analyze the potential role of immune recognition determinants in the early development of oral cancer. In this study, we examined whether SCC that undergo transformation and development in the absence of specific immunity exhibit differences in tumorigenicity that relate to differences in expression of CD80, CD86 or MHC class I. Mucosal keratinocytes from BALB/c mice were transformed in vitro with 4-nitroquinolone-1-oxide (4-NQO) and inoculated into SCID mice to obtain tumorigenic cell lines. Five SCC cell lines were re-isolated from tumors, and 4 retained cytokeratin and beta4-integrin markers of epithelial origin. Their growth was compared in BALB/c and in congenic SCID mice to establish whether the cell lines exhibit differences in immunogenicity. Three lines that showed slower growth or completely regressed when implanted in immune competent hosts retained or developed increased expression of CD80 during development in SCID mice. Conversely, 2 SCC lines that lost expression of CD80 after passage in vivo grew progressively in immune-competent hosts. MHC-class-I and CD86 expression did not correlate with tumorigenicity. These observations provide evidence that decreased expression of CD80 may serve as a marker for increased tumorigenicity during early development of oral SCC. The development of this new murine oral SCC model should prove useful in determining the potential effects of CD80 expression on the immune pathogenesis and therapy of SCC. JF - International journal of cancer AU - Thomas, G R AU - Chen, Z AU - Oechsli, M N AU - Hendler, F J AU - Van Waes, C AD - Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892-1419, USA. Y1 - 1999/07/30/ PY - 1999 DA - 1999 Jul 30 SP - 377 EP - 384 VL - 82 IS - 3 SN - 0020-7136, 0020-7136 KW - 4-nitroquinolone-1-oxide KW - 0 KW - Antigens, CD80 KW - Biomarkers, Tumor KW - Histocompatibility Antigens Class I KW - Quinolones KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - Index Medicus KW - Clone Cells KW - Animals KW - Histocompatibility Antigens Class I -- immunology KW - Mice KW - Mice, Inbred BALB C KW - 4-Nitroquinoline-1-oxide -- analogs & derivatives KW - Severe Combined Immunodeficiency -- immunology KW - Phenotype KW - 4-Nitroquinoline-1-oxide -- pharmacology KW - Lymphocyte Count KW - Immunocompetence KW - Animals, Congenic KW - Mice, SCID KW - Cell Line, Transformed KW - Male KW - Quinolones -- pharmacology KW - Carcinoma, Squamous Cell -- immunology KW - Mouth Neoplasms -- immunology KW - Antigens, CD80 -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69878149?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Decreased+expression+of+CD80+is+a+marker+for+increased+tumorigenicity+in+a+new+murine+model+of+oral+squamous-cell+carcinoma.&rft.au=Thomas%2C+G+R%3BChen%2C+Z%3BOechsli%2C+M+N%3BHendler%2C+F+J%3BVan+Waes%2C+C&rft.aulast=Thomas&rft.aufirst=G&rft.date=1999-07-30&rft.volume=82&rft.issue=3&rft.spage=377&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of the Bacteriophage T4 Transcriptional Activator, MotA, to T4 Middle Promoter DNA: Evidence for both Major and Minor Groove Contacts AN - 17323938; 4577757 AB - During infection, the bacteriophage T4 transcriptional activator MotA, the co-activator AsiA, and host RNA polymerase are needed to transcribe from T4 middle promoters. Middle promoters contain a -10 region recognized by the sigma super(70)subunit of RNA polymerase and a MotA box centered at -30 that is bound by MotA. We have investigated how the loss or modification of base determinants within the MotA box sequence 5'TTTGCTTTA3' (positions -34 to -26 of a middle promoter) affects MotA function. Gel retardation assays with mutant MotA boxes are consistent with the idea that MotA uses minor groove contacts upstream and major groove contacts downstream of the center GC, and does not require any specific base feature at the C.G base-pair at position -30. In particular, the 5-methyl residue on the thymine residue at position -29, a major groove contact, contributes to MotA binding, while converting the T.A at -32 to a C.I base-pair, a change that affects the major but nor the minor groove, yields a MotA box that is similar to wild-type. However, methylation interference analyses indicate that neither the binding of MotA nor the binding of polymerase/MotA/AsiA to the middle promoter P sub(uvsX)is inhibited by premethylation of guanine and adenine residues, suggesting that binding does not require minor groove contact with any specific T.A base-pair. Using gel retardation analyses, we calculate an apparent dissociation constant of 130 nM for MotA binding to the wild-type MotA box. Previous work has shown that the N-terminal region of MotA is needed for an interaction between MotA and sigma super(70). We suggest that this MotA- sigma super(70)interaction helps to stabilize the relatively weak interaction of MotA with the -30 region of middle promoter DNA. JF - Journal of Molecular Biology AU - Sharma, M AU - Marshall, P AU - Hinton, D M AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, MD, USA Y1 - 1999/07/30/ PY - 1999 DA - 1999 Jul 30 SP - 905 EP - 915 PB - Academic Press VL - 290 IS - 5 SN - 0022-2836, 0022-2836 KW - AsiA protein KW - MotA protein KW - Virology & AIDS Abstracts; Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Phage T4 KW - DNA-directed RNA polymerase KW - DNA KW - Transcription activators KW - Base pairs KW - N 14930:Transcription factors KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17323938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Binding+of+the+Bacteriophage+T4+Transcriptional+Activator%2C+MotA%2C+to+T4+Middle+Promoter+DNA%3A+Evidence+for+both+Major+and+Minor+Groove+Contacts&rft.au=Sharma%2C+M%3BMarshall%2C+P%3BHinton%2C+D+M&rft.aulast=Sharma&rft.aufirst=M&rft.date=1999-07-30&rft.volume=290&rft.issue=5&rft.spage=905&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/10.1006%2Fjmbi.1999.2928 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage T4; Transcription activators; DNA; DNA-directed RNA polymerase; Base pairs DO - http://dx.doi.org/10.1006/jmbi.1999.2928 ER - TY - JOUR T1 - Improved in vivo stability of actinium-225 macrocyclic complexes. AN - 69918862; 10425108 AB - The favorable nuclear properties of actinium-225 ((225)Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free (225)Ac, a series of ligands were evaluated for stability in vivo. Loss of (225)Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and (225)Ac-HEHA showed exceptional stability in vivo. (225)Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the (225)Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed. JF - Journal of medicinal chemistry AU - Deal, K A AU - Davis, I A AU - Mirzadeh, S AU - Kennel, S J AU - Brechbiel, M W AD - National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, Bethesda, Maryland 20892, USA. Y1 - 1999/07/29/ PY - 1999 DA - 1999 Jul 29 SP - 2988 EP - 2992 VL - 42 IS - 15 SN - 0022-2623, 0022-2623 KW - Acetates KW - 0 KW - Chelating Agents KW - Ligands KW - Organometallic Compounds KW - Radioisotopes KW - Radiopharmaceuticals KW - actinium 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''''-hexaacetic acid KW - Actinium KW - NIK1K0956U KW - Index Medicus KW - Drug Stability KW - Animals KW - Mice KW - Tissue Distribution KW - Mice, Inbred BALB C KW - Female KW - Organometallic Compounds -- pharmacokinetics KW - Acetates -- pharmacokinetics KW - Radiopharmaceuticals -- pharmacokinetics KW - Chelating Agents -- chemistry KW - Radiopharmaceuticals -- chemical synthesis KW - Acetates -- chemical synthesis KW - Chelating Agents -- chemical synthesis KW - Acetates -- chemistry KW - Radiopharmaceuticals -- chemistry KW - Organometallic Compounds -- chemical synthesis KW - Organometallic Compounds -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69918862?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+medicinal+chemistry&rft.atitle=Improved+in+vivo+stability+of+actinium-225+macrocyclic+complexes.&rft.au=Deal%2C+K+A%3BDavis%2C+I+A%3BMirzadeh%2C+S%3BKennel%2C+S+J%3BBrechbiel%2C+M+W&rft.aulast=Deal&rft.aufirst=K&rft.date=1999-07-29&rft.volume=42&rft.issue=15&rft.spage=2988&rft.isbn=&rft.btitle=&rft.title=Journal+of+medicinal+chemistry&rft.issn=00222623&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-31 N1 - Date created - 1999-08-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. AN - 69895969; 10423464 AB - Among patients with fever and neutropenia during chemotherapy for cancer who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous treatment. We conducted a randomized, double-blind, placebo-controlled study of patients (age, 5 to 74 years) who had fever and neutropenia during chemotherapy for cancer. Neutropenia was expected to be present for no more than 10 days in these patients, and they had to have no other underlying conditions. Patients were assigned to receive either oral ciprofloxacin plus amoxicillin-clavulanate or intravenous ceftazidime. They were hospitalized until fever and neutropenia resolved. A total of 116 episodes were included in each group (84 patients in the oral-therapy group and 79 patients in the intravenous-therapy group). The mean neutrophil counts at admission were 81 per cubic millimeter and 84 per cubic millimeter, respectively; the mean duration of neutropenia was 3.4 and 3.8 days, respectively. Treatment was successful without the need for modifications in 71 percent of episodes in the oral-therapy group and 67 percent of episodes in the intravenous-therapy group (difference between groups, 3 percent; 95 percent confidence interval, -8 percent to 15 percent; P=0.48). Treatment was considered to have failed because of the need for modifications in the regimen in 13 percent and 32 percent of episodes, respectively (P<0.001) and because of the patient's inability to tolerate the regimen in 16 percent and 1 percent of episodes, respectively (P<0.001). There were no deaths. The incidence of intolerance of the oral antibiotics was 16 percent, as compared with 8 percent for placebo (P=0.07). In hospitalized low-risk patients who have fever and neutropenia during cancer chemotherapy, empirical therapy with oral ciprofloxacin and amoxicillin-clavulanate is safe and effective. JF - The New England journal of medicine AU - Freifeld, A AU - Marchigiani, D AU - Walsh, T AU - Chanock, S AU - Lewis, L AU - Hiemenz, J AU - Hiemenz, S AU - Hicks, J E AU - Gill, V AU - Steinberg, S M AU - Pizzo, P A AD - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/07/29/ PY - 1999 DA - 1999 Jul 29 SP - 305 EP - 311 VL - 341 IS - 5 SN - 0028-4793, 0028-4793 KW - Anti-Bacterial Agents KW - 0 KW - Antineoplastic Agents KW - Clavulanic Acid KW - 23521W1S24 KW - Ciprofloxacin KW - 5E8K9I0O4U KW - Amoxicillin KW - 804826J2HU KW - Ceftazidime KW - 9M416Z9QNR KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Ceftazidime -- administration & dosage KW - Fever of Unknown Origin -- drug therapy KW - Aged KW - Ciprofloxacin -- adverse effects KW - Child KW - Amoxicillin -- adverse effects KW - Clavulanic Acid -- administration & dosage KW - Ciprofloxacin -- administration & dosage KW - Clavulanic Acid -- adverse effects KW - Adult KW - Adolescent KW - Bacterial Infections -- drug therapy KW - Male KW - Administration, Oral KW - Drug Therapy, Combination -- adverse effects KW - Neoplasms -- drug therapy KW - Ceftazidime -- adverse effects KW - Amoxicillin -- administration & dosage KW - Double-Blind Method KW - Infusions, Intravenous KW - Child, Preschool KW - Drug Therapy, Combination -- administration & dosage KW - Neoplasms -- complications KW - Middle Aged KW - Female KW - Fever -- etiology KW - Neutropenia -- etiology KW - Anti-Bacterial Agents -- adverse effects KW - Anti-Bacterial Agents -- administration & dosage KW - Fever -- drug therapy KW - Neutropenia -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69895969?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=A+double-blind+comparison+of+empirical+oral+and+intravenous+antibiotic+therapy+for+low-risk+febrile+patients+with+neutropenia+during+cancer+chemotherapy.&rft.au=Freifeld%2C+A%3BMarchigiani%2C+D%3BWalsh%2C+T%3BChanock%2C+S%3BLewis%2C+L%3BHiemenz%2C+J%3BHiemenz%2C+S%3BHicks%2C+J+E%3BGill%2C+V%3BSteinberg%2C+S+M%3BPizzo%2C+P+A&rft.aulast=Freifeld&rft.aufirst=A&rft.date=1999-07-29&rft.volume=341&rft.issue=5&rft.spage=305&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-29 N1 - Date created - 1999-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 1999 Jul 29;341(5):362-3 [10423472] N Engl J Med. 2000 Jan 6;342(1):55; author reply 56-8 [10627209] N Engl J Med. 2000 Jan 6;342(1):55-6; author reply 56-8 [10627210] N Engl J Med. 2000 Jan 6;342(1):56; author reply 56-8 [10627212] N Engl J Med. 2000 Jan 6;342(1):56; author reply 56-8 [10627211] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alternative, non-secretase processing of Alzheimer's beta-amyloid precursor protein during apoptosis by caspase-6 and -8. AN - 69896075; 10409650 AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Although the pathogenesis of AD is unknown, it is widely accepted that AD is caused by extracellular accumulation of a neurotoxic peptide, known as Abeta. Mutations in the beta-amyloid precursor protein (APP), from which Abeta arises by proteolysis, are associated with some forms of familial AD (FAD) and result in increased Abeta production. Two other FAD genes, presenilin-1 and -2, have also been shown to regulate Abeta production; however, studies examining the biological role of these FAD genes suggest an alternative theory for the pathogenesis of AD. In fact, all three genes have been shown to regulate programmed cell death, hinting at the possibility that dysregulation of apoptosis plays a primary role in causing neuronal loss in AD. In an attempt to reconcile these two hypotheses, we investigated APP processing during apoptosis and found that APP is processed by the cell death proteases caspase-6 and -8. APP is cleaved by caspases in the intracellular portion of the protein, in a site distinct from those processed by secretases. Moreover, it represents a general effect of apoptosis, because it occurs during cell death induced by several stimuli both in T cells and in neuronal cells. JF - The Journal of biological chemistry AU - Pellegrini, L AU - Passer, B J AU - Tabaton, M AU - Ganjei, J K AU - D'Adamio, L AD - T-Cell Apoptosis Unit, Laboratory of Cellular and Molecular Immunology, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07/23/ PY - 1999 DA - 1999 Jul 23 SP - 21011 EP - 21016 VL - 274 IS - 30 SN - 0021-9258, 0021-9258 KW - Amyloid beta-Protein Precursor KW - 0 KW - Amyloid Precursor Protein Secretases KW - EC 3.4.- KW - Endopeptidases KW - CASP6 protein, human KW - EC 3.4.22.- KW - CASP8 protein, human KW - CASP9 protein, human KW - Caspase 6 KW - Caspase 8 KW - Caspase 9 KW - Caspases KW - Aspartic Acid Endopeptidases KW - EC 3.4.23.- KW - BACE1 protein, human KW - EC 3.4.23.46 KW - Index Medicus KW - Humans KW - Protein Processing, Post-Translational KW - Jurkat Cells KW - Endopeptidases -- metabolism KW - Mutation KW - Apoptosis KW - Amyloid beta-Protein Precursor -- metabolism KW - Alzheimer Disease -- metabolism KW - Amyloid beta-Protein Precursor -- genetics KW - Caspases -- metabolism KW - Alzheimer Disease -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69896075?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Alternative%2C+non-secretase+processing+of+Alzheimer%27s+beta-amyloid+precursor+protein+during+apoptosis+by+caspase-6+and+-8.&rft.au=Pellegrini%2C+L%3BPasser%2C+B+J%3BTabaton%2C+M%3BGanjei%2C+J+K%3BD%27Adamio%2C+L&rft.aulast=Pellegrini&rft.aufirst=L&rft.date=1999-07-23&rft.volume=274&rft.issue=30&rft.spage=21011&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-26 N1 - Date created - 1999-08-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3, cs70 II. Brain AN - 18378443; 5360722 AB - Most cell divisions in the mouse brain have ceased by 14 days after birth. Therefore, spontaneous mutations that occur in brain cells can be assumed to be fixed by replication during brain development. Spontaneous and ethylnitrosourea (ENU)-induced reverse mutations at a single AT base pair were measured in brain tissue by using mice transgenic for PhiX174 am3, cs70. The line (am54) has 50 PhiX genomes per haploid genome integrated in a tandem array and is maintained by random breeding on a C57BL/6 background. For mutagenesis studies, homozygous am54 males were mated to non-transgenic C57BL6/J females. Four-day old offspring from this cross were treated with 50 mg/kg ENU and were euthanized at 68-80 days of age. The ENU-treated animals had a significantly higher frequency of am3 revertants in brain than did concurrent controls. In a second experiment, hemizygous male offspring (85 to 94 days old) were treated with 150 mg/kg ENU and euthanized at various post-injection intervals (3, 10 and 110 days). The revertant frequencies 3 and 10 days after treatment were not significantly different from control values. At the 110 days post-injection interval, however, the average revertant frequency in the treated group was significantly lower than controls. In a second study animals were euthanized 3, 10 and 74 days after treatment. Two groups (3 and 74 days post-injection) also showed a significant decrease in the revertant frequency as compared to controls. Additional sets of adult animals were treated with 50 and 150 mg/kg ENU and were euthanized 195 to 201 days after treatment. The average revertant frequency of the animals that were treated with 50 or 150 mg/kg ENU was not significantly different from the control value. Thus, although an increase in mutant frequency is detected in the PhiX174 system when neonatal mice are treated with ENU, treatment of mature mice with ENU did not result in an increase in the mutant frequency. Moreover, under certain conditions, ENU-produced a significantly lower mutant frequency than was observed in the control animals. This decrease in the revertant frequency among the treated animals was likely due to selective killing of cells with a higher spontaneous revertant frequency than cells with lower frequency. JF - Mutation Research-Genetic Toxicology and Environmental Mutagenesis AU - Malling, H V AU - R. Newbold, R AU - Lewis, S AU - Barnett, L AU - Weaver, R P AD - Mammalian Mutagenesis Group, Laboratory of Toxicology, Environmental Toxicology Program, National Institute Of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park NC USA Y1 - 1999/07/21/ PY - 1999 DA - 1999 Jul 21 SP - 85 EP - 95 PB - Elsevier Science VL - 444 IS - 1 SN - 1383-5718, 1383-5718 KW - am3 gene KW - mice KW - Genetics Abstracts; Toxicology Abstracts KW - X 24200:Nitrosamines & related compounds KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18378443?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.atitle=Mutagenesis+of+a+single+AT+basepair+in+mice+transgenic+for+PhiX174+am3%2C+cs70+II.+Brain&rft.au=Malling%2C+H+V%3BR.+Newbold%2C+R%3BLewis%2C+S%3BBarnett%2C+L%3BWeaver%2C+R+P&rft.aulast=Malling&rft.aufirst=H&rft.date=1999-07-21&rft.volume=444&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Genetic+Toxicology+and+Environmental+Mutagenesis&rft.issn=13835718&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - An aspartate residue at the extracellular boundary of TMII and an arginine residue in TMVII of the gastrin-releasing peptide receptor interact to facilitate heterotrimeric G protein coupling. AN - 69907133; 10413511 AB - The mammalian bombesin receptor subfamily of G protein-coupled receptors currently consists of the gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor, and bombesin receptor subtype 3. All three receptors contain a conserved aspartate residue (D98) at the extracellular boundary of transmembrane domain II and a conserved arginine residue (R309) near the extracellular boundary of transmembrane domain VII. To evaluate the functional role of these residues, site-directed GRP-R mutants were expressed in fibroblasts and assayed for their ability to both bind agonist and catalyze exchange of guanine nucleotides. Alanine substitution at GRP-R position 98 or 309 reduced agonist binding affinity by 24- and 56-fold, respectively, compared to wild-type GRP-R. Single swap GRP-R mutations either resulted in no receptor expression in the membrane (D98R) or the protein was not able to bind agonist (R309D). In contrast, the double swap mutation (D98R/R309D) had high-affinity agonist binding, reduced from wild-type GRP-R by only 6-fold. In situ reconstitution of urea-extracted membranes expressing either wild-type or mutant (D98A or R309A) GRP-R with G(q) indicated that alanine substitution greatly reduced G protein catalytic exchange compared to wild-type GRP-R. The D98R/R309D GRP-R had both a higher intrinsic basal activity and a higher overall catalytic exchange activity compared to wild-type; however, the wild-type GRP-R produced a larger agonist-stimulated response relative to the double swap mutant. Taken together, these data show that GRP-R residues D98 and R309 are critical for efficient coupling of GRP-R to G(q). Furthermore, our findings are consistent with a salt bridge interaction between these two polar and oppositely charged amino acids that maintains the proper receptor conformation necessary to interact with G proteins. JF - Biochemistry AU - Donohue, P J AU - Sainz, E AU - Akeson, M AU - Kroog, G S AU - Mantey, S A AU - Battey, J F AU - Jensen, R T AU - Northup, J K AD - Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA. Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 9366 EP - 9372 VL - 38 IS - 29 SN - 0006-2960, 0006-2960 KW - Ligands KW - 0 KW - Peptide Fragments KW - Receptors, Bombesin KW - Guanosine Diphosphate KW - 146-91-8 KW - Aspartic Acid KW - 30KYC7MIAI KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Arginine KW - 94ZLA3W45F KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Clone Cells KW - 3T3 Cells KW - Animals KW - Peptide Fragments -- genetics KW - Guanosine Diphosphate -- metabolism KW - Amino Acid Sequence KW - Mice KW - Mutagenesis, Site-Directed KW - Amino Acid Substitution -- genetics KW - Molecular Sequence Data KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Protein Binding -- genetics KW - Protein Structure, Tertiary KW - Catalysis KW - Receptors, Bombesin -- genetics KW - Aspartic Acid -- metabolism KW - Aspartic Acid -- genetics KW - Arginine -- metabolism KW - Extracellular Space -- metabolism KW - Arginine -- genetics KW - GTP-Binding Proteins -- metabolism KW - Receptors, Bombesin -- metabolism KW - Receptors, Bombesin -- biosynthesis KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69907133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=An+aspartate+residue+at+the+extracellular+boundary+of+TMII+and+an+arginine+residue+in+TMVII+of+the+gastrin-releasing+peptide+receptor+interact+to+facilitate+heterotrimeric+G+protein+coupling.&rft.au=Donohue%2C+P+J%3BSainz%2C+E%3BAkeson%2C+M%3BKroog%2C+G+S%3BMantey%2C+S+A%3BBattey%2C+J+F%3BJensen%2C+R+T%3BNorthup%2C+J+K&rft.aulast=Donohue&rft.aufirst=P&rft.date=1999-07-20&rft.volume=38&rft.issue=29&rft.spage=9366&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-15 N1 - Date created - 1999-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. AN - 69903029; 10411946 AB - This report describes a modulatory action of lithium and glutamate on the activity of serine/threonine kinase Akt-1. Lithium is most commonly used to treat bipolar disorder, but the mechanism of its therapeutic action remains unknown. We have recently demonstrated that lithium protects against glutamate-induced excitotoxicity in cultured brain neurons and in an animal model of cerebral ischemia. This study was undertaken to investigate the role of Akt-1, activated by the phosphatidylinositol 3-kinase (PI 3-K) signaling pathway, in mediating glutamate excitotoxicity and lithium protection in cerebellar granule cells. High levels of phosphorylation and activity of Akt-1 were detected in cerebellar neurons cultured in the presence of serum. Protracted treatment with selective PI 3-K inhibitors, wortmannin and LY294002, abolished Akt-1 activity and induced neuronal death that could be reduced by long-term lithium pretreatment. Exposure of cells to glutamate induced a rapid and reversible loss of Akt-1 phosphorylation and kinase activity. These effects were closely correlated with excitotoxicity and caspase 3 activation and were prevented by phosphatase inhibitors, okadaic acid and caliculin A. Long-term lithium pretreatment suppressed glutamate-induced loss of Akt-1 activity and accelerated its recovery toward the control levels. Lithium treatment alone induced rapid increase in PI 3-K activity, and Akt-1 phosphorylation with accompanying kinase activation, which was blocked by PI 3-K inhibitors. Lithium also increased the phosphorylation of glycogen synthase kinase-3 (GSK-3), a downstream physiological target of Akt. Thus, modulation of Akt-1 activity appears to play a key role in the mechanism of glutamate excitotoxicity and lithium neuroprotection. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Chalecka-Franaszek, E AU - Chuang, D M AD - Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1272, USA. Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 8745 EP - 8750 VL - 96 IS - 15 SN - 0027-8424, 0027-8424 KW - Androstadienes KW - 0 KW - Chromones KW - Enzyme Inhibitors KW - Morpholines KW - Neuroprotective Agents KW - Neurotoxins KW - Proto-Oncogene Proteins KW - 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one KW - 31M2U1DVID KW - Glutamic Acid KW - 3KX376GY7L KW - Lithium KW - 9FN79X2M3F KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Akt1 protein, rat KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - Casp3 protein, rat KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Morpholines -- pharmacology KW - Androstadienes -- pharmacology KW - Neurotoxins -- pharmacology KW - Caspases -- metabolism KW - Neuroprotective Agents -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Cell Survival -- drug effects KW - Chromones -- pharmacology KW - Cells, Cultured KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Phosphatidylinositol 3-Kinases -- antagonists & inhibitors KW - Protein-Serine-Threonine Kinases -- metabolism KW - Neurons -- drug effects KW - Protein-Serine-Threonine Kinases -- antagonists & inhibitors KW - Glutamic Acid -- pharmacology KW - Lithium -- pharmacology KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69903029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Lithium+activates+the+serine%2Fthreonine+kinase+Akt-1+and+suppresses+glutamate-induced+inhibition+of+Akt-1+activity+in+neurons.&rft.au=Chalecka-Franaszek%2C+E%3BChuang%2C+D+M&rft.aulast=Chalecka-Franaszek&rft.aufirst=E&rft.date=1999-07-20&rft.volume=96&rft.issue=15&rft.spage=8745&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-23 N1 - Date created - 1999-08-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Neurochem. 1993 Feb;60(2):652-8 [8380439] Mol Pharmacol. 1992 Aug;42(2):210-6 [1355259] Science. 1995 Mar 31;267(5206):2003-6 [7701324] Trends Neurosci. 1995 Feb;18(2):58-60 [7537408] Cell. 1995 Jun 2;81(5):727-36 [7774014] EMBO J. 1995 Sep 1;14(17):4288-95 [7556070] Nature. 1995 Dec 21-28;378(6559):785-9 [8524413] Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5699-704 [8650155] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8455-9 [8710892] EMBO J. 1996 Dec 2;15(23):6541-51 [8978681] FEBS Lett. 1996 Dec 16;399(3):333-8 [8985174] Science. 1997 Jan 31;275(5300):661-5 [9005851] Science. 1997 Jan 31;275(5300):665-8 [9005852] J Neurosci. 1997 Mar 1;17(5):1548-60 [9030615] Neurosci Biobehav Rev. 1997 Mar;21(2):193-206 [9062943] Lab Invest. 1997 May;76(5):603-12 [9166279] Science. 1997 Jul 25;277(5325):567-70 [9228007] J Biol Chem. 1997 Oct 3;272(40):25326-32 [9312151] Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11657-62 [9326666] Cell. 1997 Oct 17;91(2):231-41 [9346240] EMBO J. 1997 Oct 15;16(20):6151-61 [9321394] J Neurochem. 1997 Dec;69(6):2336-44 [9375664] Genes Dev. 1998 Feb 15;12(4):502-13 [9472019] Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2642-7 [9482940] J Biol Chem. 1998 May 22;273(21):13150-6 [9582355] Neuroreport. 1998 Jun 22;9(9):2081-4 [9674597] J Biol Chem. 1998 Oct 9;273(41):26596-602 [9756898] Science. 1998 Nov 13;282(5392):1318-21 [9812896] J Biol Chem. 1998 Dec 4;273(49):32377-9 [9829964] Nature. 1998 Dec 10;396(6711):584-7 [9859994] J Biol Chem. 1999 Mar 5;274(10):6039-42 [10037682] J Neurosci. 1999 Mar 15;19(6):1940-51 [10066247] Am J Psychiatry. 1990 May;147(5):615-20 [2109539] Biochem Biophys Res Commun. 1992 Jan 31;182(2):593-9 [1370886] Trends Neurosci. 1994 Sep;17(9):359-65 [7529438] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Attenuation of the recombinant human parainfluenza virus type 3 cp45 candidate vaccine virus is augmented by importation of the respiratory syncytial virus cpts530 L polymerase mutation. AN - 69894065; 10405364 AB - A phenylalanine to leucine mutation at position 521 in the L polymerase of cpts530, a live-attenuated respiratory syncytial virus (RSV) cold-passaged (cp), temperature-sensitive (ts) candidate vaccine, specifies the ts and attenuation (att) phenotypes. Sequence alignment of this region in the L proteins of several distantly related paramyxoviruses revealed that this phenylalanine is conserved. Using reverse genetics, the analogous phenylalanine at position 456 in the L protein of wild-type PIV3 was mutagenized to leucine (F456L). The resulting virus, designated r456(L), was ts (40 degrees C shut-off temperature of plaque formation), and its replication in the upper, but not the lower, respiratory tract of hamsters was 10-fold reduced compared with that of the recombinant wild-type PIV3 (rwt). Thus the phenylalanine to leucine mutation specified a similar level of temperature sensitivity and attenuation in two distantly related paramyxoviruses. We next sought to determine whether the addition of this mutation to the L protein of two rPIV3 candidate vaccine viruses, one bearing the three cp45 ts missense mutations in the L protein (rcp45(L)) and the other bearing all 15 cp45 mutations (rcp45), would further attenuate the viruses in vivo. Each rcp45 derivative to which the F456L mutation was added exhibited an increased level of temperature sensitivity. Furthermore rcp45(L)-456 and rcp45-456 were 100- to 1000-fold more restricted in replication in hamsters than their rcp45(L) and rcp45 parents. Despite the high level of restriction of replication in hamsters, immunization with rcp45-456 induced a moderate level of resistance to replication of PIV3 challenge virus. In contrast to the highly restricted replication observed in hamsters, rcp45-456 was only fivefold more restricted in the respiratory tract of chimpanzees than rcp45 and induced a comparable, moderate to high level of PIV3-specific serum antibodies. rcp45 and rcp45-456 viruses isolated from chimpanzees throughout the 2-week course of replication maintained the level of temperature sensitivity of their respective input viruses, illustrating their phenotypic stability. Thus the acquisition of the F456L mutation by the cp45 virus resulted in a small, incremental increase in its level of attenuation, indicating its possible usefulness in the fine tuning of the level of attenuation of the cp45 vaccine candidate. The ability to transfer mutations identified in heterologous paramyxoviruses, which in this case represent different subfamilies, greatly enhances our ability to rapidly develop novel parainfluenza virus candidate vaccines. Copyright 1999 Academic Press. JF - Virology AU - Skiadopoulos, M H AU - Surman, S R AU - St Claire, M AU - Elkins, W R AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0720, USA. mskiadopoulos@atlas.niaid.nih.giv Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 125 EP - 135 VL - 260 IS - 1 SN - 0042-6822, 0042-6822 KW - Recombinant Proteins KW - 0 KW - Vaccines, Attenuated KW - Viral Proteins KW - Viral Vaccines KW - parainfluenza 3 virus, L Protein KW - DNA-Directed RNA Polymerases KW - EC 2.7.7.6 KW - Index Medicus KW - Virus Replication KW - Phenotype KW - Animals KW - Respiratory Syncytial Viruses -- genetics KW - Humans KW - Temperature KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Amino Acid Substitution KW - Pan troglodytes KW - Cricetinae KW - Viral Proteins -- genetics KW - Parainfluenza Virus 3, Human -- genetics KW - DNA-Directed RNA Polymerases -- metabolism KW - Viral Proteins -- metabolism KW - Parainfluenza Virus 3, Human -- physiology KW - Mutation KW - Parainfluenza Virus 3, Human -- immunology KW - DNA-Directed RNA Polymerases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69894065?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Attenuation+of+the+recombinant+human+parainfluenza+virus+type+3+cp45+candidate+vaccine+virus+is+augmented+by+importation+of+the+respiratory+syncytial+virus+cpts530+L+polymerase+mutation.&rft.au=Skiadopoulos%2C+M+H%3BSurman%2C+S+R%3BSt+Claire%2C+M%3BElkins%2C+W+R%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Skiadopoulos&rft.aufirst=M&rft.date=1999-07-20&rft.volume=260&rft.issue=1&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retroviral Marking and Transplantation of Rhesus Hematopoietic Cells by Nonmyeloablative Conditioning AN - 17364406; 4586281 AB - The ability to engraft significant numbers of genetically modified hematopoietic stem and progenitor cells without the requirement for fully myeloablative conditioning therapy is a highly desirable goal for the treatment of many nonmalignant hematologic disorders. The aims of this study were to examine, in nonhuman primates (rhesus), (1) the effects of pretreatment of host animals with cytokines (G-CSF and SCF), i.e., before nonmyeloablative irradiation, on the degree and duration of neo gene marking of circulating leukocytes after autologous cell reinfusion and (2) to compare transduction of primitive hematopoietic target cells in the presence of our standard transduction cytokine combination of IL-3, IL-6, and stem cell factor (SCF) and in the presence of an alternative combination containing SCF, G-CSF, and the thrombopoietin analog MGDF. Cytokine-mobilized rhesus peripheral blood progenitor/stem cells (PBSCs) were enriched for CD34 super(+) cells and transduced with neo vectors (either G1Na or LNL6) for 96 hr in cultures containing rhIL-3, rhIL-6, and rhSCF or MGDF, rhSCF, and rhG-CSF and cryopreserved. Four animals underwent minimal myeloablative conditioning with 500 cGy irradiation with or without pretreatment with SCF and G-CSF, followed by reinfusion of the cryopreserved cells on the subsequent day. Neutrophil nadirs ( less than or equal to 500/mm super(3)) were 0-3 days in duration; there were no significant periods of severe thrombocytopenia. Marking of circulating granulocytes and mononuclear cells was extensive and durable in all animals (exceeding 12% in the mononuclear cells of one animal) and persisted beyond the final sampling time in all animals (up to 33 weeks). No difference in extent or duration of marking was attributable to either cytokine presensitization of recipients prior to irradiation, or to the substitution of MDGF and G-CSF for IL-3 and IL-6 during transduction. JF - Human Gene Therapy AU - Huhn, R D AU - Tisdale, J F AU - Agricola, B AU - Metzger, ME AU - Donahue, R E AU - Dunbar, CE AD - Hematology Branch, National Heart, Lung, and Blood Institute, Building 10, Room 7C103, 9000 Rockville Pike, Bethesda, MD 20892, USA, dunbarc@gwgate.nhlbi.nih.gov Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 1783 EP - 1790 VL - 10 IS - 11 SN - 1043-0342, 1043-0342 KW - man KW - monkeys KW - Macaca mulatta KW - Retrovirus KW - SCF protein KW - granulocyte colony-stimulating factor KW - hemopoiesis KW - neo gene KW - stem cell factor KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Interleukin 6 KW - Gene therapy KW - Interleukin 3 KW - Expression vectors KW - Stem cells KW - Cytokines KW - Hemopoiesis KW - Transduction KW - Signal transduction KW - W3 33181:Gene therapy vectors KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17364406?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Retroviral+Marking+and+Transplantation+of+Rhesus+Hematopoietic+Cells+by+Nonmyeloablative+Conditioning&rft.au=Huhn%2C+R+D%3BTisdale%2C+J+F%3BAgricola%2C+B%3BMetzger%2C+ME%3BDonahue%2C+R+E%3BDunbar%2C+CE&rft.aulast=Huhn&rft.aufirst=R&rft.date=1999-07-20&rft.volume=10&rft.issue=11&rft.spage=1783&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950017464 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Signal transduction; Hemopoiesis; Stem cells; Cytokines; Interleukin 3; Interleukin 6; Gene therapy; Expression vectors; Transduction DO - http://dx.doi.org/10.1089/10430349950017464 ER - TY - JOUR T1 - Here's the hook: Similar substrate binding sites in the chaperone domains of Clp and Lon AN - 17360760; 4569816 AB - Protein quality control mechanisms are essential to ensure the proper levels of functional proteins within the cell and to eliminate nonfunctional proteins from the cell. To this end, the cell maintains an array of molecular chaperones to help fold proteins into their native conformations, prevent aggregation, and assist in assembly of multiprotein complexes, along with ATP-dependent proteases to degrade damaged or improperly synthesized proteins. Also, the intracellular concentrations or activities of a limited number of normal cellular proteins are modulated by these same proteases and chaperones. These natural protein targets are often key regulatory proteins involved in vital processes such as cell division, stress responses, and developmental changes. To avoid potentially lethal damage to inappropriate cellular components the chaperones and proteases have evolved rather complex energy-dependent mechanisms to assure accurate substrate recognition. JF - Proceedings of the National Academy of Sciences, USA AU - Wickner, S AU - Maurizi, M R AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health Bethesda, MD 20892, wickners@dc37a.nci.nih.gov Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 8318 EP - 8320 VL - 96 IS - 15 SN - 0027-8424, 0027-8424 KW - regulation KW - binding KW - Clp proteinase KW - Lon proteinase KW - Microbiology Abstracts B: Bacteriology KW - Endopeptidase La KW - Proteins KW - Chaperones KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17360760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Here%27s+the+hook%3A+Similar+substrate+binding+sites+in+the+chaperone+domains+of+Clp+and+Lon&rft.au=Wickner%2C+S%3BMaurizi%2C+M+R&rft.aulast=Wickner&rft.aufirst=S&rft.date=1999-07-20&rft.volume=96&rft.issue=15&rft.spage=8318&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.15.8318 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Endopeptidase La; Chaperones; Proteins DO - http://dx.doi.org/10.1073/pnas.96.15.8318 ER - TY - JOUR T1 - Crystal structure of ERA: A GTPase-dependent cell cycle regulator containing an RNA binding motif AN - 17359729; 4569835 AB - ERA forms a unique family of GTPase. It is widely conserved and essential in bacteria. ERA functions in cell cycle control by coupling cell division with growth rate. ERA homologues also are found in eukaryotes. Here we report the crystal structure of ERA from Escherichia coli. The structure has been determined at 2.4-Aa resolution. It reveals a two- domain arrangement of the molecule: an N-terminal domain that resembles p21 Ras and a C-terminal domain that is unique. Structure-based topological search of the C domain fails to reveal any meaningful match, although sequence analysis suggests that it contains a KH domain. KH domains are RNA binding motifs that usually occur in tandem repeats and exhibit low sequence similarity except for the well-conserved segment VIGxxGxxIK. We have identified a beta alpha alpha beta fold that contains the VIGxxGxxIK sequence and is shared by the C domain of ERA and the KH domain. We propose that this beta alpha alpha beta fold is the RNA binding motif, the minimum structural requirement for RNA binding. ERA dimerizes in crystal. The dimer formation involves a significantly distorted switch II region, which may shed light on how ERA protein regulates downstream events. JF - Proceedings of the National Academy of Sciences, USA AU - Chen, X AU - Court, D L AU - Ji, X AD - Biomolecular Structure Group, Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, P.O. Box B, Frederick, MD 21702, jix@ncifcrf.gov Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 8396 EP - 8401 VL - 96 IS - 15 SN - 0027-8424, 0027-8424 KW - ERA protein KW - Microbiology Abstracts B: Bacteriology KW - RNA-binding protein KW - Cell cycle KW - Crystal structure KW - Escherichia coli KW - Guanosinetriphosphatase KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17359729?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Crystal+structure+of+ERA%3A+A+GTPase-dependent+cell+cycle+regulator+containing+an+RNA+binding+motif&rft.au=Chen%2C+X%3BCourt%2C+D+L%3BJi%2C+X&rft.aulast=Chen&rft.aufirst=X&rft.date=1999-07-20&rft.volume=96&rft.issue=15&rft.spage=8396&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.15.8396 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; RNA-binding protein; Guanosinetriphosphatase; Crystal structure; Cell cycle DO - http://dx.doi.org/10.1073/pnas.96.15.8396 ER - TY - JOUR T1 - JE-2147: A dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1 AN - 17294281; 4569885 AB - We designed, synthesized, and identified JE- 2147, an allophenylnorstatine-containing dipeptide HIV protease inhibitor (PI), which is potent against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, and various clinical HIV-1 strains in vitro. Drug-resistant clinical HIV-1 strains, isolated from seven patients who had failed 9-11 different anti-HIV therapeutics after 32-83 months, had a variety of drug-resistance-related amino acid substitutions and were highly and invariably resistant to all of the currently available anti-HIV agents. JE-2147 was, however, extremely potent against all such drug-resistant strains, with IC sub(50) values ranging from 13-41 nM (<2-fold changes in IC sub(50) compared with that of wild-type HIV-1). The emergence of JE-2147-resistant HIV-1 variants in vitro was substantially delayed compared with that of HIV-1 resistant to another allophenylnorstatine-containing compound, KNI-272, and other related PIs. Structural analysis revealed that the presence of a flexible P2' moiety is important for the potency of JE-2147 toward wild-type and mutant viruses. These data suggest that the use of flexible components may open a new avenue for designing PIs that resist the emergence of PI-resistant HIV-1. Further development of JE-2147 for treating patients harboring multi-PI-resistant HIV-1 is warranted. JF - Proceedings of the National Academy of Sciences, USA AU - Yoshimura, K AU - Kato, R AU - Yusa, K AU - Kavlick, M F AU - Maroun, V AU - Nguyen, A AU - Mimoto, T AU - Ueno, T AU - Shintani, M AU - Falloon, J AU - Masur, H AU - Hayashi, H AU - Erickson, J AU - Mitsuya, H AD - Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, hmitsuya@helix.nih.gov Y1 - 1999/07/20/ PY - 1999 DA - 1999 Jul 20 SP - 8675 EP - 8680 VL - 96 IS - 15 SN - 0027-8424, 0027-8424 KW - HIV-1 KW - HIV-2 KW - Human immunodeficiency virus 1 KW - Human immunodeficiency virus 2 KW - SIV KW - allophenylnorstatine KW - proteinase inhibitors KW - simian immunodeficiency virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - HIV-1 retropepsin KW - Drug resistance KW - Drug sensitivity testing KW - Antiviral agents KW - Multidrug resistance KW - Simian immunodeficiency virus KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17294281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=JE-2147%3A+A+dipeptide+protease+inhibitor+%28PI%29+that+potently+inhibits+multi-PI-resistant+HIV-1&rft.au=Yoshimura%2C+K%3BKato%2C+R%3BYusa%2C+K%3BKavlick%2C+M+F%3BMaroun%2C+V%3BNguyen%2C+A%3BMimoto%2C+T%3BUeno%2C+T%3BShintani%2C+M%3BFalloon%2C+J%3BMasur%2C+H%3BHayashi%2C+H%3BErickson%2C+J%3BMitsuya%2C+H&rft.aulast=Yoshimura&rft.aufirst=K&rft.date=1999-07-20&rft.volume=96&rft.issue=15&rft.spage=8675&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.15.8675 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Human immunodeficiency virus 2; Simian immunodeficiency virus; Drug sensitivity testing; HIV-1 retropepsin; Drug resistance; Antiviral agents; Multidrug resistance DO - http://dx.doi.org/10.1073/pnas.96.15.8675 ER - TY - JOUR T1 - Production of epidermal growth factor related ligands in tumorigenic and benign human lung epithelial cells. AN - 69926460; 10424781 AB - We recently demonstrated that human lung epithelial cells, overexpressing ErbB-2, formed tumors in nude mice only when high levels of transforming growth factor alpha (TGFalpha) were produced. Cells transfected with a TGFalpha antisense vector failed to form tumors in nude mice. In order to further evaluate the importance, for tumorigenicity, of TGFalpha and its stimulation of ErbB family signalling, the production of other EGF family growth factors by these human lung epithelial cells was studied. We demonstrate for the first time that both tumorigenic and non-tumorigenic human lung epithelial cells produced, in addition to TGFalpha, amphiregulin, betacellulin, heparin-binding EGF and heregulin. These data suggest that human lung epithelial cells have the potential for multifactorial modulation of ErbB receptor family signalling through control of ligand as well as receptor production. In this system, the probable importance of TGFalpha-stimulated signaling for tumorigenicity is supported by its 13-fold higher production in tumorigenic as compared with non-tumorigenic cells and the 2-fold or lower differences observed in production of the other epidermal growth factor (EGF) family ligands. JF - Cancer letters AU - Fernandes, A M AU - Hamburger, A W AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/07/19/ PY - 1999 DA - 1999 Jul 19 SP - 55 EP - 63 VL - 142 IS - 1 SN - 0304-3835, 0304-3835 KW - Ligands KW - 0 KW - Transforming Growth Factor alpha KW - Epidermal Growth Factor KW - 62229-50-9 KW - Receptor, ErbB-2 KW - EC 2.7.10.1 KW - Index Medicus KW - Gene Expression Regulation, Neoplastic KW - Animals KW - Genes, erbB-2 KW - Humans KW - Mice KW - Cell Transformation, Neoplastic KW - Receptor, ErbB-2 -- genetics KW - Transforming Growth Factor alpha -- genetics KW - Neoplasms, Experimental -- genetics KW - Transforming Growth Factor alpha -- biosynthesis KW - Lung Neoplasms -- genetics KW - Neoplasms, Experimental -- metabolism KW - Lung -- pathology KW - Lung -- metabolism KW - Neoplasms, Experimental -- pathology KW - Epidermal Growth Factor -- metabolism KW - Receptor, ErbB-2 -- biosynthesis KW - Lung Neoplasms -- pathology KW - Lung Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69926460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Production+of+epidermal+growth+factor+related+ligands+in+tumorigenic+and+benign+human+lung+epithelial+cells.&rft.au=Fernandes%2C+A+M%3BHamburger%2C+A+W%3BGerwin%2C+B+I&rft.aulast=Fernandes&rft.aufirst=A&rft.date=1999-07-19&rft.volume=142&rft.issue=1&rft.spage=55&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-16 N1 - Date created - 1999-08-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3'-azido-3'-deoxythymidine (AZT) transplacental perfusion kinetics and DNA incorporation in normal human placentas perfused with AZT. AN - 70835209; 10517977 AB - Vertical transmission of the human immunodeficiency virus 1 (HIV-1) is reduced from approximately 25% to approximately 7% as a result of 3'-azido-3'-deoxythymidine (AZT) therapy given during pregnancy; however, the consequences of transplacental AZT exposure to the fetus remain unknown. To address the extent and kinetics of AZT transfer across the human placenta, perfusion studies have been performed with fresh uninfected human placentas perfused with 0.5, 1. 0 and 5.0 mg AZT/ml for 2 h using a dual recirculating single cotyledon perfusion apparatus [T.I. Ala-Kokko, P. Pienimaki, R. Herva, A.I. Hollmen, O. Pelkonen, K. Vähäkangas, Transfer of lidocaine and bupivacaine across the isolated perfused human placenta, Pharmacol. Toxicol. 77 (1995) 142-148]. For two placentas, samples of perfusion effluent were taken every 15 min from the maternal and fetal sides of the apparatus and AZT levels were determined by AZT radioimmunoassay (RIA). At the end of the perfusion, AZT-DNA incorporation into placental DNA was determined by AZT-RIA. The concentration of AZT in the fetal perfusate increased with time, along with a concomitant slow decrease in the concentration of AZT in the maternal perfusates. For three different placentas, at 2 h after the start of perfusion, AZT-DNA incorporation values (molecules of AZT/10(6) nucleotides) were 11.8 for the 0.5 mg AZT/ml perfusate, 13.7 for the 1.0 mg AZT/ml perfusion, and 42.0 for the 5 mg AZT/ml perfusion. An additional placenta perfused with 1 mg AZT/ml did not have detectable values of AZT incorporated into DNA (data not shown). The data show that AZT crosses the human placenta and becomes rapidly incorporated into DNA of placental tissue in a dose-dependent fashion, suggesting that even short exposures to this drug might induce fetal genotoxicity and might also inhibit maternal-fetal viral transmission. JF - Mutation research AU - Olivero, O A AU - Parikka, R AU - Poirier, M C AU - Vähäkangas, K AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. oliveroo@dc37a.nci.nih.gov Y1 - 1999/07/16/ PY - 1999 DA - 1999 Jul 16 SP - 41 EP - 47 VL - 428 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Infectious Disease Transmission, Vertical KW - Maternal-Fetal Exchange KW - Perfusion -- instrumentation KW - HIV Infections -- transmission KW - Humans KW - In Vitro Techniques KW - HIV Infections -- prevention & control KW - HIV Infections -- drug therapy KW - Pregnancy Complications, Infectious -- drug therapy KW - HIV-1 KW - Female KW - Pregnancy KW - Zidovudine -- pharmacokinetics KW - Anti-HIV Agents -- pharmacokinetics KW - Zidovudine -- metabolism KW - Zidovudine -- adverse effects KW - Anti-HIV Agents -- metabolism KW - DNA -- metabolism KW - Anti-HIV Agents -- adverse effects KW - Placenta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70835209?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=3%27-azido-3%27-deoxythymidine+%28AZT%29+transplacental+perfusion+kinetics+and+DNA+incorporation+in+normal+human+placentas+perfused+with+AZT.&rft.au=Olivero%2C+O+A%3BParikka%2C+R%3BPoirier%2C+M+C%3BV%C3%A4h%C3%A4kangas%2C+K&rft.aulast=Olivero&rft.aufirst=O&rft.date=1999-07-16&rft.volume=428&rft.issue=1-2&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-08 N1 - Date created - 1999-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53 mutation spectrum and load: the generation of hypotheses linking the exposure of endogenous or exogenous carcinogens to human cancer. AN - 70833968; 10517975 AB - The activation of protooncogenes and inactivation of tumor suppressor genes in affected cells are considered as the core events that provide a selective growth advantage and clonal expansion during the multistep process of carcinogenesis. Somatic mutations, induced by exogenous or endogenous mechanisms, were found to alter the normal functions of the p53 tumor suppressor gene. p53 is the most prominent example of tumor suppressor genes because it is mutated in about half of all human cancer. In contrast to other tumor suppressor genes (like APC and RB), about 80% of p53 mutations are missense mutations that lead to amino acid substitutions in proteins and can alter the protein conformation and increase the stability of p53. These changes can also alter the sequence-specific DNA binding and transcription factor activity of p53. These abnormalities can abrogate p53 dependent pathways involved in important cellular functions like cell-cycle control, DNA repair, differentiation, genomic plasticity and programmed cell death. A number of different carcinogens have been found to cause different characteristic mutations in the p53 gene. For example, exposure to ultraviolet light is correlated with transition mutations at dipyrimidine sites; aflatoxin B(1) exposure is correlated with a G:C to T:A transversion that leads to a serine substitution at residue 249 of p53 in hepatocellular carcinoma; and exposure to cigarette smoke is correlated with G:C to T:A transversions in lung carcinoma. Therefore, measuring the characteristic p53 mutation load or frequency of mutated alleles in nontumorous tissue (before the clonal expansion of mutated cells), can generate hypotheses, e.g., providing a molecular linkage between exposure to a particular carcinogen and cancer, and identifying individuals at increased cancer risk. JF - Mutation research AU - Hussain, S P AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg. 37, Rm. 2C05, Bethesda, MD 20892, USA. Y1 - 1999/07/16/ PY - 1999 DA - 1999 Jul 16 SP - 23 EP - 32 VL - 428 IS - 1-2 SN - 0027-5107, 0027-5107 KW - Carcinogens KW - 0 KW - Carcinogens, Environmental KW - Codon KW - Nitric Oxide KW - 31C4KY9ESH KW - Benzo(a)pyrene KW - 3417WMA06D KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Nitric Oxide -- toxicity KW - Codon -- genetics KW - Sunlight -- adverse effects KW - Humans KW - Benzo(a)pyrene -- toxicity KW - Aflatoxin B1 -- toxicity KW - Carcinogens, Environmental -- toxicity KW - Models, Biological KW - Genes, p53 KW - Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Mutation KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70833968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+research&rft.atitle=p53+mutation+spectrum+and+load%3A+the+generation+of+hypotheses+linking+the+exposure+of+endogenous+or+exogenous+carcinogens+to+human+cancer.&rft.au=Hussain%2C+S+P%3BHarris%2C+C+C&rft.aulast=Hussain&rft.aufirst=S&rft.date=1999-07-16&rft.volume=428&rft.issue=1-2&rft.spage=23&rft.isbn=&rft.btitle=&rft.title=Mutation+research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-08 N1 - Date created - 1999-11-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Altered glycosylation sites of the delta subunit of the acetylcholine receptor (AChR) reduce alpha delta association and receptor assembly. AN - 69886563; 10400680 AB - We have used mutagenesis to investigate the potential N-glycosylation sites in the delta subunit of the mouse muscle acetylcholine receptor (AChR). Of the three sites, Asn76, Asn143, and Asn169, only the first two were glycosylated when the delta subunit was expressed in COS cells. Because the heterologously expressed delta subunit was similar in its properties to that expressed in C2 muscle cells, the sites of glycosylation are likely to be the same in both cases. In COS cells, mutations of the delta subunit that prevented glycosylation at either of the sites did not change its metabolic stability nor its steady-state level. These results are in contrast to those found previously for the alpha subunit, in which glycosylation at a single site metabolically stabilized the polypeptide (Blount, P., and Merlie, J. P. (1990) J. Cell Biol. 111, 2613-2622). Mutations of the delta subunit that prevented glycosylation, however, decreased its ability to form an alpha delta heterodimer when the alpha and delta subunit were expressed together. When all four subunits of the AChR (alpha, beta, delta, and epsilon) were coexpressed, mutation of the delta subunit to prevent glycosylation resulted in a reduced amount of fully assembled AChR and reduced surface AChR levels, consistent with the role of the heterodimer in the assembly reaction. These results suggest that glycosylation of the delta subunit at both Asn76 and Asn143 is needed for its efficient folding and/or its subsequent interaction with the alpha subunit. JF - The Journal of biological chemistry AU - Ramanathan, V K AU - Hall, Z W AD - Section on Synaptic Mechanisms, Laboratory of Cellular and Molecular Regulation, NIMH, National Institutes of Health, Bethesda, Maryland 20892, USA. Ramanathan@sbphrd.com Y1 - 1999/07/16/ PY - 1999 DA - 1999 Jul 16 SP - 20513 EP - 20520 VL - 274 IS - 29 SN - 0021-9258, 0021-9258 KW - DNA, Complementary KW - 0 KW - Receptors, Cholinergic KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Muscles -- cytology KW - Animals KW - COS Cells KW - Dimerization KW - Muscles -- metabolism KW - Mice KW - Glycosylation KW - Receptors, Cholinergic -- genetics KW - Receptors, Cholinergic -- metabolism KW - Receptors, Cholinergic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69886563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Altered+glycosylation+sites+of+the+delta+subunit+of+the+acetylcholine+receptor+%28AChR%29+reduce+alpha+delta+association+and+receptor+assembly.&rft.au=Ramanathan%2C+V+K%3BHall%2C+Z+W&rft.aulast=Ramanathan&rft.aufirst=V&rft.date=1999-07-16&rft.volume=274&rft.issue=29&rft.spage=20513&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of Siamese cassia leaves on the activities of chemical carcinogen metabolizing enzymes and on mammary gland carcinogenesis in the rat AN - 17337673; 4595715 AB - Male Wistar rats were fed AIN-76 semipurified diet or diet containing 5% ground lyophilized Siamese cassia leaves for 2 weeks before sacrifice. Hepatic S9 fractions were prepared and assayed for the level of cytochrome P450 (P450), the activities of monooxygenase, i.e., aniline hydroxylase (ANH), aminopyrine-N-demethylase (AMD) as well as the capacity to metabolically activate the mutagenicities of aflatoxin B sub(1) (AFB sub(1)) and benzo(a)pyrene (B(a)P). In addition, the activities of detoxificating enzymes such as glutathione-S-transferase (GST) and UDP-glucuronyltransferase (UGT) were also measured. It was found that feeding of Siamese cassia leaves significantly reduced the activities of hepatic ANH and AMD as well as the capacity to activate the mutagenicity of AFB sub(1) towards Salmonella typhimurium TA100, being 31, 73 and 41% of control group, respectively. It also slightly decreased, but not significantly, the capacity to activate the mutagenicity of B(a)P towards S. typhimurium YG1029. On the other hand, however, the activities of both GST and UGT were markedly increased in those animals, being 250 and 220% of control animals. The anticarcinogenic potential of Siamese cassia leaves was also investigated in female Sprague Dawley rats treated with 9,10-dimethyl-1,2-benzanthracene (DMBA). The animals were fed control diet or diet containing ground lyophilized Siamese cassia leaves 2 weeks prior to and 1 week after intragastrically administration of DMBA, and then they were placed on a pellet diet for additional 25 weeks. Interestingly, it was found that feeding of diet containing 2.5 and 4% Siamese cassia leaves resulted in a significant decrease in the multiplicity of mammary gland tumors as well as a slight delay of the onset of tumor development. The incidence of tumors in the group fed 4% Siamese cassia leaves, but not in the 2.5% group, was lowered, although not significantly, than that of control group. The results in the present study therefore demonstrated that Siamese cassia leaves possess phase II enzyme inducing property as well as the ability to reduce some phase I enzyme activities in rat liver. This Thai vegetable also exhibit cancer chemopreventive potential, at least against DMBA-induced mammary gland carcinogenesis which may be partly due to phase II inducing capacity as well as phase I inhibitory activity. JF - Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis AU - Tepsuwan, A AU - Kupradinun, P AU - Kusamran, W R AD - Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Rama VI Road Bangkok Thailand Y1 - 1999/07/16/ PY - 1999 DA - 1999 Jul 16 SP - 363 EP - 373 PB - Elsevier VL - 428 IS - 1-2 SN - 0027-5107, 0027-5107 KW - aflatoxin B1 KW - benzo(a)pyrene KW - cytochrome P450 KW - Toxicology Abstracts KW - Mammary gland KW - Carcinogenicity KW - 9,10-Dimethyl-1,2-benzanthracene KW - Enzymes KW - Glutathione transferase KW - Antitumor agents KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17337673?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.atitle=Effect+of+Siamese+cassia+leaves+on+the+activities+of+chemical+carcinogen+metabolizing+enzymes+and+on+mammary+gland+carcinogenesis+in+the+rat&rft.au=Tepsuwan%2C+A%3BKupradinun%2C+P%3BKusamran%2C+W+R&rft.aulast=Tepsuwan&rft.aufirst=A&rft.date=1999-07-16&rft.volume=428&rft.issue=1-2&rft.spage=363&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Fundamental+and+Molecular+Mechanisms+of+Mutagenesis&rft.issn=00275107&rft_id=info:doi/10.1016%2FS1383-5742%2899%2900062-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenicity; 9,10-Dimethyl-1,2-benzanthracene; Glutathione transferase; Antitumor agents; Enzymes; Mammary gland DO - http://dx.doi.org/10.1016/S1383-5742(99)00062-9 ER - TY - JOUR T1 - The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. AN - 69941434; 10435597 AB - Both DR4 and DR5 have recently been identified as membrane death receptors that are activated by their ligand TRAIL to engage the intracellular apoptotic machinery. TRID (also named as TRAIL-R3) is an antagonist decoy receptor and lacks the cytoplasmic death domain. TRID protects from TRAIL-induced apoptosis by competing with DR4 and DR5 for binding to TRAIL. TRID has been shown to be overexpressed in normal human tissues but not in malignantly transformed cell lines. DR5 is a p53-regulated gene and we have recently reported that DR5 expression is induced in response to genotoxic stress in both a p53-dependent and independent manner (Sheikh et al., 1998). In the current study, we demonstrate that TRID gene expression is also induced by the genotoxic agents ionizing radiation and methyl methanesulfonate (MMS) in predominantly p53 wild-type cells, whereas UV-irradiation does not induce TRID gene expression. Consistent with these results, exogenous wild-type p53 also upregulates the expression of endogenous TRID in p53-null cells. Thus, TRID appears to be a p53 target gene that is regulated by genotoxic stress in a p53-dependent manner. Using primary gastrointestinal tract (GIT) tumors and their matching normal tissue, we also demonstrate for the first time that TRID expression is enhanced in primary tumors of the GIT. It is, therefore, possible that TRID overexpressing GIT tumors may gain a selective growth advantage by escaping from TRAIL-induced apoptosis. JF - Oncogene AU - Sheikh, M S AU - Huang, Y AU - Fernandez-Salas, E A AU - El-Deiry, W S AU - Friess, H AU - Amundson, S AU - Yin, J AU - Meltzer, S J AU - Holbrook, N J AU - Fornace, A J AD - Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07/15/ PY - 1999 DA - 1999 Jul 15 SP - 4153 EP - 4159 VL - 18 IS - 28 SN - 0950-9232, 0950-9232 KW - Apoptosis Regulatory Proteins KW - 0 KW - DNA, Neoplasm KW - GPI-Linked Proteins KW - Membrane Glycoproteins KW - Mutagens KW - Neoplasm Proteins KW - Receptors, Tumor Necrosis Factor KW - Receptors, Tumor Necrosis Factor, Member 10c KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFRSF10C protein, human KW - TNFSF10 protein, human KW - Tumor Necrosis Factor Decoy Receptors KW - Tumor Necrosis Factor-alpha KW - Tumor Suppressor Protein p53 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Stomach Neoplasms -- pathology KW - Adenocarcinoma -- metabolism KW - Ultraviolet Rays KW - Humans KW - Stress, Physiological -- genetics KW - Aged KW - Adenocarcinoma -- genetics KW - Mutagens -- pharmacology KW - Esophageal Neoplasms -- pathology KW - Methyl Methanesulfonate -- pharmacology KW - Tumor Cells, Cultured KW - Esophageal Neoplasms -- metabolism KW - Genes, p53 KW - Carcinoma, Squamous Cell -- pathology KW - Aged, 80 and over KW - Adult KW - Carcinoma, Squamous Cell -- genetics KW - Colonic Neoplasms -- pathology KW - Male KW - Protein Conformation KW - Colonic Neoplasms -- genetics KW - Stomach Neoplasms -- metabolism KW - Gamma Rays KW - Temperature KW - Carcinoma, Squamous Cell -- metabolism KW - Organ Specificity KW - Adenocarcinoma -- pathology KW - Stomach Neoplasms -- genetics KW - Esophageal Neoplasms -- genetics KW - Middle Aged KW - Colonic Neoplasms -- metabolism KW - Tumor Necrosis Factor-alpha -- metabolism KW - Female KW - Membrane Glycoproteins -- metabolism KW - DNA, Neoplasm -- radiation effects KW - Gastrointestinal Neoplasms -- genetics KW - Neoplasm Proteins -- biosynthesis KW - Tumor Suppressor Protein p53 -- physiology KW - DNA Damage KW - Gene Expression Regulation, Neoplastic -- drug effects KW - DNA Repair -- genetics KW - DNA, Neoplasm -- drug effects KW - Apoptosis -- genetics KW - Neoplasm Proteins -- physiology KW - Carcinoma -- pathology KW - Receptors, Tumor Necrosis Factor -- biosynthesis KW - Receptors, Tumor Necrosis Factor -- physiology KW - Neoplasm Proteins -- genetics KW - Tumor Suppressor Protein p53 -- chemistry KW - DNA, Neoplasm -- genetics KW - Gene Expression Regulation, Neoplastic -- radiation effects KW - Gastrointestinal Neoplasms -- metabolism KW - Gastrointestinal Neoplasms -- pathology KW - Carcinoma -- metabolism KW - Receptors, Tumor Necrosis Factor -- genetics KW - Tumor Suppressor Protein p53 -- deficiency KW - Gene Expression Regulation, Neoplastic -- genetics KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69941434?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=The+antiapoptotic+decoy+receptor+TRID%2FTRAIL-R3+is+a+p53-regulated+DNA+damage-inducible+gene+that+is+overexpressed+in+primary+tumors+of+the+gastrointestinal+tract.&rft.au=Sheikh%2C+M+S%3BHuang%2C+Y%3BFernandez-Salas%2C+E+A%3BEl-Deiry%2C+W+S%3BFriess%2C+H%3BAmundson%2C+S%3BYin%2C+J%3BMeltzer%2C+S+J%3BHolbrook%2C+N+J%3BFornace%2C+A+J&rft.aulast=Sheikh&rft.aufirst=M&rft.date=1999-07-15&rft.volume=18&rft.issue=28&rft.spage=4153&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-13 N1 - Date created - 1999-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Redistribution and phosphorylation of occludin during opening and resealing of tight junctions in cultured epithelial cells. AN - 69930181; 10430658 AB - We studied the expression, distribution, and phosphorylation of the tight junction (TJ) protein occludin in confluent MDCK cell monolayers following three procedures for opening and resealing of TJs. When Ca(2+) is transiently removed from the culture medium, the TJs open and the cells separate from each other, but the occludin band around each cell is retained. When Ca(2+) is reintroduced, the TJs reseal. When the monolayers are exposed to prolonged Ca(2+) starvation the cells maintain contact, but occludin disappears from the cell borders and can be detected only in a cytoplasmic compartment. When Ca(2+) is reintroduced, new TJs are assembled and the transepithelial electrical resistance (TER) is reestablished in about 20 hr. Monolayers treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) show a different pattern of TJ opening: the cell-cell contact is maintained but the TJ strand network, as seen in freeze-fracture replicas, becomes discontinuous. Occludin is still localized at the cell periphery, but in a pattern of distribution that matches the discontinuous TJ. These TJs do not reseal even 24 hr after removal of the TPA. Western blot analysis showed that the 62-65 kD double band of occludin did not change with these treatments. However, in vivo phosphorylation analysis showed that the TPA treatment reduced the phosphorylation levels of occludin, while the prolonged Ca(2+) starvation completely dephosphorylated the two occludin bands. In addition, a highly phosphorylated 71 kD band that immunoprecipitates with occludin is not present when TJ is opened by the Ca(2+) removal. Phosphoaminoacid analysis showed that the 62-65 kD occludin bands are phosphorylated on serine and threonine, while the 71 kD band was phosphorylated exclusively on serine. Our results provide further evidence that phosphorylation of occludin is an important step in regulating TJ formation and permeability. JF - The Journal of membrane biology AU - Farshori, P AU - Kachar, B AD - Section on Structural Cell Biology, National Institute on Deafness and Other Communication Disorders, National Institute of Health, Bethesda, MD 20892, USA. Y1 - 1999/07/15/ PY - 1999 DA - 1999 Jul 15 SP - 147 EP - 156 VL - 170 IS - 2 SN - 0022-2631, 0022-2631 KW - Chelating Agents KW - 0 KW - Membrane Proteins KW - Occludin KW - Egtazic Acid KW - 526U7A2651 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Chelating Agents -- pharmacology KW - Animals KW - Calcium Signaling -- drug effects KW - Blotting, Western KW - Phosphorylation KW - Gene Expression KW - Electric Impedance KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Calcium -- pharmacology KW - Egtazic Acid -- pharmacology KW - Cell Line KW - Epithelial Cells -- ultrastructure KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Tight Junctions -- physiology KW - Membrane Proteins -- metabolism KW - Tight Junctions -- drug effects KW - Membrane Proteins -- genetics KW - Membrane Proteins -- drug effects KW - Tight Junctions -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69930181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+membrane+biology&rft.atitle=Redistribution+and+phosphorylation+of+occludin+during+opening+and+resealing+of+tight+junctions+in+cultured+epithelial+cells.&rft.au=Farshori%2C+P%3BKachar%2C+B&rft.aulast=Farshori&rft.aufirst=P&rft.date=1999-07-15&rft.volume=170&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+membrane+biology&rft.issn=00222631&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-24 N1 - Date created - 1999-09-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A p21(Waf1/Cip1)carboxyl-terminal peptide exhibited cyclin-dependent kinase-inhibitory activity and cytotoxicity when introduced into human cells. AN - 69901154; 10416614 AB - In the present study, we report the cyclin-dependent kinase (Cdk)-inhibitory activity of a series of p21waf1/cip1 (p21) peptide fragments spanning the whole protein against the cyclin D1/Cdk4 and cyclin E/Cdk2 enzymes. The most potent p21 peptide tested in our initial peptide series, designated W10, spanned amino acids 139 to 164, a region of p21 that has been found independently to bind to proliferating cell nuclear antigen and also to inhibit Cdk activity. We go on to report the importance of putative beta-strand and 3(10)-helix motifs in the W10 peptide for cyclin-dependent kinase-inhibitory activity. We also describe the cellular activity of W10 and derivatives that were chemically linked to an antennapedia peptide, the latter segment acting as a cell membrane carrier. We found that the W10AP peptide exhibited growth inhibition that resulted from necrosis in human lymphoma CA46 cells. Furthermore, regions in the W10 peptide responsible for Cdk-inhibition were also important for the degree of this cellular activity. These studies provide insights that may eventually, through further design, yield agents for the therapy of cancer. JF - Cancer research AU - Mutoh, M AU - Lung, F D AU - Long, Y Q AU - Roller, P P AU - Sikorski, R S AU - O'Connor, P M AD - Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/07/15/ PY - 1999 DA - 1999 Jul 15 SP - 3480 EP - 3488 VL - 59 IS - 14 SN - 0008-5472, 0008-5472 KW - Antennapedia Homeodomain Protein KW - 0 KW - CDKN1A protein, human KW - Cyclin E KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Homeodomain Proteins KW - Neoplasm Proteins KW - Nuclear Proteins KW - Peptide Fragments KW - Proliferating Cell Nuclear Antigen KW - Transcription Factors KW - Cyclin D1 KW - 136601-57-5 KW - Index Medicus KW - Tumor Cells, Cultured -- drug effects KW - Homeodomain Proteins -- pharmacology KW - Humans KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Necrosis KW - Molecular Sequence Data KW - Flow Cytometry KW - Microscopy, Electron KW - Cell Membrane -- metabolism KW - Proliferating Cell Nuclear Antigen -- metabolism KW - Cyclin D1 -- antagonists & inhibitors KW - Peptide Fragments -- toxicity KW - Neoplasm Proteins -- antagonists & inhibitors KW - Burkitt Lymphoma -- pathology KW - Cyclin E -- antagonists & inhibitors KW - Cyclins -- toxicity KW - Peptide Fragments -- chemistry KW - Cyclins -- chemistry KW - Burkitt Lymphoma -- enzymology KW - Cyclins -- pharmacology KW - Peptide Fragments -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69901154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+p21%28Waf1%2FCip1%29carboxyl-terminal+peptide+exhibited+cyclin-dependent+kinase-inhibitory+activity+and+cytotoxicity+when+introduced+into+human+cells.&rft.au=Mutoh%2C+M%3BLung%2C+F+D%3BLong%2C+Y+Q%3BRoller%2C+P+P%3BSikorski%2C+R+S%3BO%27Connor%2C+P+M&rft.aulast=Mutoh&rft.aufirst=M&rft.date=1999-07-15&rft.volume=59&rft.issue=14&rft.spage=3480&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-12 N1 - Date created - 1999-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Systemic Administration of a Recombinant Vaccinia Virus Expressing the Cytosine Deaminase Gene and Subsequent Treatment with 5-Fluorocytosine Leads to Tumor-specific Gene Expression and Prolongation of Survival in Mice AN - 17383956; 4601479 AB - Suicide gene therapy using the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) has shown promising results for the treatment of colon carcinoma cells in vitro. Efficient viral infection and tumor-specific gene delivery is crucial for clinically measurable treatment effects. After proving efficient gene transfer in vitro, we demonstrate here that genes can be delivered to metastatic liver tumors in vivo in a highly selective manner using systemic delivery of a thymidine kinase-deleted (TK-) recombinant vaccinia virus (Western Reserve strain). When the vector was administered systemically in C57BL/6 mice or nude/athymic mice with established disseminated MC38 liver metastases, transgene expression in tumors was usually 1,000- to 10,000-fold higher compared with other organs (n = 160; P < 0.00001). This tumor-specific gene transfer leads to significant tumor responses and subsequent survival benefits after the transfer of the CD gene to liver metastases and subsequent systemic treatment with the prodrug 5-FC (P < 0.0001). We describe reporter gene and survival experiments both in immunocompetent and athymic nude mice, establishing a gene expression pattern over time and characterizing the treatment effects of the virus delivery/prodrug system. Cure rates of up to 30% in animals with established liver metastases show that suicide gene therapy using TK- vaccinia virus as a vector may be a promising system for the clinical application of tumor-directed gene therapy. JF - Cancer Research AU - Gnant, MFX AU - Puhlmann, M AU - Alexander, HR Jr AU - Bartlett, D L AD - Surgical Metabolism Section, Surgery Branch, National Cancer Institute, NIH, Building 10, Room 2B07, 9000 Rockville Pike, Bethesda, MD 20892, dbart@nih.gov Y1 - 1999/07/15/ PY - 1999 DA - 1999 Jul 15 SP - 3396 EP - 3403 VL - 59 IS - 14 SN - 0008-5472, 0008-5472 KW - mice KW - 5-fluorocytosine KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Colon KW - Gene therapy KW - Colorectal carcinoma KW - Cytosine deaminase KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17383956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Systemic+Administration+of+a+Recombinant+Vaccinia+Virus+Expressing+the+Cytosine+Deaminase+Gene+and+Subsequent+Treatment+with+5-Fluorocytosine+Leads+to+Tumor-specific+Gene+Expression+and+Prolongation+of+Survival+in+Mice&rft.au=Gnant%2C+MFX%3BPuhlmann%2C+M%3BAlexander%2C+HR+Jr%3BBartlett%2C+D+L&rft.aulast=Gnant&rft.aufirst=MFX&rft.date=1999-07-15&rft.volume=59&rft.issue=14&rft.spage=3396&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene therapy; Cytosine deaminase; Colon; Colorectal carcinoma; Expression vectors ER - TY - JOUR T1 - Preconception Urethane or Chromium(III) Treatment of Male Mice: Multiple Neoplastic and Non-neoplastic Changes in Offspring AN - 17264989; 4561177 AB - Increase in neoplasia in offspring after preconception exposure of parents presents puzzling features such as high frequency of effects and lack of Mendelian inheritance. The present study examined the hypothesis that preconception carcinogenesis involves an increase in the rate of occurrence of neoplasms with a spontaneous incidence. Male NIH Swiss mice (12 per group) were exposed 2 weeks before mating (once, ip) to urethane (1.5 g/kg) or chromium(III) chloride (1 mmol/kg). Offspring (48-78/sex/group) were examined for all grossly apparent changes when moribund or at natural death, followed by histopathological diagnosis and statistical analysis. Significant exposure-related changes occurred in multiple organs. Ten to 20 percent of offspring showed changes related to paternal exposure, including at least one sired by most treated males. Pheochromocytomas occurred in both male and female offspring after both treatments, with none in controls. These neoplasms are rare in mice and suggest endocrine dysfunction as a component of preconception carcinogenesis. This was supported by increases in thyroid follicular cell and Harderian gland tumors, ovarian cysts, and uterine abnormalities. Lung tumors were increased in female offspring only. Effects seen in offspring only after paternal urethane exposure were an increase in preneoplasia /neoplasia in the glandular stomach (males) and in females, increased lymphoma but decreased incidence of histiocytic sarcoma. Increases in incidence of male reproductive gland tumors and of renal non-neoplastic lesions occurred only after chromium exposure. Thus, preconception exposure of fathers to toxicants had a significant impact on both neoplastic and non-neoplastic changes in almost all tissues in which these lesions often occur naturally during the aging process. JF - Toxicology and Applied Pharmacology AU - Yu, W AU - Sipowicz, MA AU - Haines, D C AU - Birely, L AU - Diwan, BA AU - Riggs, C W AU - Kasprzak, K S AU - Anderson, L M AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, 21702, Maryland, andersol@mail.ncifcrf.gov Y1 - 1999/07/15/ PY - 1999 DA - 1999 Jul 15 SP - 161 EP - 176 PB - Academic Press VL - 158 IS - 2 SN - 0041-008X, 0041-008X KW - histopathology KW - mice KW - parental effects KW - Toxicology Abstracts KW - Urethan KW - Metals KW - Chromium KW - Carcinogenesis KW - Neoplasia KW - X 24164:Pathology KW - X 24154:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17264989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=Preconception+Urethane+or+Chromium%28III%29+Treatment+of+Male+Mice%3A+Multiple+Neoplastic+and+Non-neoplastic+Changes+in+Offspring&rft.au=Yu%2C+W%3BSipowicz%2C+MA%3BHaines%2C+D+C%3BBirely%2C+L%3BDiwan%2C+BA%3BRiggs%2C+C+W%3BKasprzak%2C+K+S%3BAnderson%2C+L+M&rft.aulast=Yu&rft.aufirst=W&rft.date=1999-07-15&rft.volume=158&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; Neoplasia; Metals; Urethan; Chromium ER - TY - JOUR T1 - Short-term effects of high-dose 17beta-estradiol in postmenopausal PD patients: a crossover study. AN - 69891315; 10408542 AB - To examine the effect of 17beta-estradiol on the severity of the cardinal signs of PD in postmenopausal women. Although the impact of estrogens on the manifestations of PD has not been subjected to rigorous study, their use is generally thought to be associated with a detrimental antidopaminergic effect. A double-blind, placebo-controlled, two-arm crossover study of high-dose transdermal 17beta-estradiol was conducted in eight postmenopausal women with mild to moderate PD, all but one of whom exhibited levodopa-induced dyskinesias. Patients were randomized initially to either hormonal treatment or placebo for 2 weeks, followed by a 2-week washout period, and then another 2-week crossover treatment period. Active treatment employed four skin patches each releasing 0.1 mg of estradiol daily, replaced every 2 to 3 days. After 10 days of treatment a significant reduction was observed in the antiparkinsonian threshold dose of IV levodopa. Mean duration and magnitude of the antiparkinsonian response to threshold or high doses of levodopa were unchanged, and dyskinesia scores were unaltered during 17beta-estradiol treatment compared with placebo. No worsening in "on" time or motor ratings with estrogen treatment was documented. 17beta-estradiol appears to display a slight prodopaminergic (or antiparkinsonian) effect without consistently altering dyskinesias. Standard postmenopausal replacement therapy with transdermal 17beta-estradiol is likely to be well tolerated by many female parkinsonian patients. JF - Neurology AU - Blanchet, P J AU - Fang, J AU - Hyland, K AU - Arnold, L A AU - Mouradian, M M AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Y1 - 1999/07/13/ PY - 1999 DA - 1999 Jul 13 SP - 91 EP - 95 VL - 53 IS - 1 SN - 0028-3878, 0028-3878 KW - Antiparkinson Agents KW - 0 KW - Delayed-Action Preparations KW - Levodopa KW - 46627O600J KW - Estradiol KW - 4TI98Z838E KW - Abridged Index Medicus KW - Index Medicus KW - Administration, Cutaneous KW - Postmenopause KW - Double-Blind Method KW - Humans KW - Cross-Over Studies KW - Aged KW - Middle Aged KW - Female KW - Estradiol -- adverse effects KW - Estradiol -- administration & dosage KW - Levodopa -- therapeutic use KW - Estradiol -- therapeutic use KW - Antiparkinson Agents -- therapeutic use KW - Parkinson Disease -- physiopathology KW - Parkinson Disease -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69891315?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurology&rft.atitle=Short-term+effects+of+high-dose+17beta-estradiol+in+postmenopausal+PD+patients%3A+a+crossover+study.&rft.au=Blanchet%2C+P+J%3BFang%2C+J%3BHyland%2C+K%3BArnold%2C+L+A%3BMouradian%2C+M+M%3BChase%2C+T+N&rft.aulast=Blanchet&rft.aufirst=P&rft.date=1999-07-13&rft.volume=53&rft.issue=1&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Neurology&rft.issn=00283878&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-09 N1 - Date created - 1999-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thiols mediate superoxide-dependent NADH modification of glyceraldehyde-3-phosphate dehydrogenase. AN - 69873612; 10391884 AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is covalently modified by NAD in the presence of nitric oxide (NO) and dithiothreitol. Replacement of NAD with NADH in the presence of SIN-1 (3-morpholinosydnonimine) and dithiothreitol increased modification 25-fold. We now demonstrate that in contrast to NO-mediated attachment of NAD, covalent attachment of NADH to GAPDH proceeds in the presence of low molecular weight thiols, independent of NO. Removal of oxygen and transition metal ions inhibited modification, consistent with a role for reactive oxygen species; inhibition by superoxide dismutase, stimulation by xanthine oxidase/hypoxanthine, and the lack of an effect of catalase supported the hypothesis that superoxide, generated from thiol oxidation, was involved. Electrospray mass spectrometry showed covalent linkage of the NADH molecule to GAPDH. Characterization of the product of phosphodiesterase cleavage demonstrated that linkage to GAPDH occurred through the nicotinamide of NADH. Lys-C digestion of GAPDH, followed by peptide isolation by high performance liquid chromatography, matrix-assisted laser desorption ionization time-of-flight analysis, and Edman sequencing, demonstrated that NADH attachment occurred at Cys-149, the active-site thiol. This thiol linkage was stable to HgCl2. Thus, linkage of GAPDH to NADH, in contrast to NAD, occurs in the presence of thiol, is independent of NO, and is mediated by superoxide. JF - The Journal of biological chemistry AU - Rivera-Nieves, J AU - Thompson, W C AU - Levine, R L AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. JR3u@virginia.edu Y1 - 1999/07/09/ PY - 1999 DA - 1999 Jul 09 SP - 19525 EP - 19531 VL - 274 IS - 28 SN - 0021-9258, 0021-9258 KW - Chelating Agents KW - 0 KW - Reactive Oxygen Species KW - Sulfhydryl Compounds KW - NAD KW - 0U46U6E8UK KW - Superoxides KW - 11062-77-4 KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - linsidomine KW - 5O5U71P6VQ KW - Cholera Toxin KW - 9012-63-9 KW - Molsidomine KW - D46583G77X KW - Catalase KW - EC 1.11.1.6 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - Glyceraldehyde-3-Phosphate Dehydrogenases KW - EC 1.2.1.- KW - Metalloendopeptidases KW - EC 3.4.24.- KW - peptidyl-Lys metalloendopeptidase KW - EC 3.4.24.20 KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Dithiothreitol KW - T8ID5YZU6Y KW - Index Medicus KW - Xanthine Oxidase -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Molsidomine -- analogs & derivatives KW - Superoxide Dismutase -- metabolism KW - Nitric Oxide -- metabolism KW - Rabbits KW - Ascorbic Acid -- pharmacology KW - Muscle, Skeletal -- enzymology KW - Chromatography, High Pressure Liquid KW - Dithiothreitol -- chemistry KW - Catalase -- metabolism KW - Chelating Agents -- pharmacology KW - Spectrophotometry KW - Nitroprusside -- pharmacology KW - Cholera Toxin -- metabolism KW - Molsidomine -- pharmacology KW - NAD -- chemistry KW - Superoxides -- pharmacology KW - Sulfhydryl Compounds -- chemistry KW - Glyceraldehyde-3-Phosphate Dehydrogenases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69873612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Thiols+mediate+superoxide-dependent+NADH+modification+of+glyceraldehyde-3-phosphate+dehydrogenase.&rft.au=Rivera-Nieves%2C+J%3BThompson%2C+W+C%3BLevine%2C+R+L%3BMoss%2C+J&rft.aulast=Rivera-Nieves&rft.aufirst=J&rft.date=1999-07-09&rft.volume=274&rft.issue=28&rft.spage=19525&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-05 N1 - Date created - 1999-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Orientation of DNA replication establishes mating-type switching pattern in S. pombe AN - 762269604; 13741234 AB - The fission yeast Schizosaccharomyces pombe normally has haploid cells of two mating types, which differ at the chromosomal locus mat1. After two consecutive asymmetric cell divisions, only one in four 'grand-daughter' cells undergoes a 'mating-type switch', in which genetic information is transferred to mat1 from the mat2-P or mat3-M donor loci. This switching pattern probably results from an imprinting event at mat1 that marks one sister chromatid in a strand-specific manner, and is related to a site-specific, double-stranded DNA break at mat1,. Here we show that the genetic imprint is a strand-specific, alkali-labile DNA modification at mat1. The DNA break is an artefact, created from theimprint during DNA purification. We also propose and test themodel that mat1 is preferentially replicated by a centromere-distal origin(s), so that the strand-specific imprint occurs only during lagging-strand synthesis. Altering the origin of replication, by inverting mat1 or introducing an origin of replication, affects the imprinting and switching efficiencies in predicted ways. Two-dimensional gel analysis confirmed that mat1 is preferentially replicated by a centromere-distal origin(s). Thus, the DNA replication machinery may confer different developmental potential to sister cells. JF - Nature AU - Dalgaard, Jacob Z AU - Klar, Amar JS AD - Gene Regulation and Chromosome Biology Laboratory, ABL-Basic Research Program, NCI Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA PY - 1999 SP - 181 EP - 184 PB - Nature Publishing Group, The Macmillan Building London N1 9XW United Kingdom VL - 400 IS - 6740 SN - 0028-0836, 0028-0836 KW - Microbiology Abstracts C: Algology, Mycology & Protozoology; Biochemistry Abstracts 2: Nucleic Acids; Aqualine Abstracts; Water Resources Abstracts KW - Testing Procedures KW - Yeasts KW - DNA biosynthesis KW - Replication KW - sister chromatids KW - Mating types KW - Imprinting KW - DNA damage KW - Cell division KW - Replication origins KW - Purification KW - Synthesis KW - Schizosaccharomyces pombe KW - AQ 00001:Water Resources and Supplies KW - N 14820:DNA Metabolism & Structure KW - SW 0540:Properties of water KW - K 03310:Genetics & Taxonomy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/762269604?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aaqualine&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=Orientation+of+DNA+replication+establishes+mating-type+switching+pattern+in+S.+pombe&rft.au=Dalgaard%2C+Jacob+Z%3BKlar%2C+Amar+JS&rft.aulast=Dalgaard&rft.aufirst=Jacob&rft.date=1999-07-08&rft.volume=400&rft.issue=6740&rft.spage=181&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/10.1038%2F22139 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-11-01 N1 - Last updated - 2015-12-23 N1 - SubjectsTermNotLitGenreText - DNA biosynthesis; DNA damage; Cell division; Replication; Replication origins; sister chromatids; Mating types; Purification; Imprinting; Yeasts; Testing Procedures; Synthesis; Schizosaccharomyces pombe DO - http://dx.doi.org/10.1038/22139 ER - TY - JOUR T1 - HIV-1 Nef increases T cell activation in a stimulus-dependent manner. AN - 69879804; 10393966 AB - Lentiviral Nef increases viral replication in vivo, plays a direct role in pathogenesis, and increases viral particle infectivity. We now find that HIV Nef also increases the activation of T cells, a cellular state required for optimal viral replication. This enhancement is stimulant-dependent. As defined by IL-2 generation, activation of T cells stimulated with classical mitogens [phorbol 12-myristate 13-acetate (PMA) + anti-CD3, PMA + phytohemagglutinin, and PMA + ionomycin] is unaffected by the expression of Nef. However, Nef increases IL-2 secretion when cells are stimulated through the T cell receptor and the costimulus receptor (CD28). This increase in activation, which depends on Nef myristylation, is caused by an increase in the number of cells reaching full activation and not by an increase in the amount of IL-2 secreted per cell. These findings demonstrate that Nef lowers the threshold of the dual-receptor T cell activation pathway. The capacity of Nef to increase T cell activity may be very important in vivo when Nef is the predominant or the only viral gene product expressed. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Schrager, J A AU - Marsh, J W AD - Laboratory of Molecular Biology, National Institute of Mental Health, 36 Convent Drive, Bethesda, MD 20892-4034, USA. Y1 - 1999/07/06/ PY - 1999 DA - 1999 Jul 06 SP - 8167 EP - 8172 VL - 96 IS - 14 SN - 0027-8424, 0027-8424 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD28 KW - Antigens, CD3 KW - Gene Products, nef KW - Interleukin-2 KW - Receptor-CD3 Complex, Antigen, T-Cell KW - nef Gene Products, Human Immunodeficiency Virus KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - AIDS/HIV KW - Humans KW - Antigens, CD28 -- physiology KW - Jurkat Cells KW - Interleukin-2 -- biosynthesis KW - Antibodies, Monoclonal -- pharmacology KW - Antigens, CD3 -- immunology KW - Cells, Cultured KW - Kinetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme-Linked Immunosorbent Assay KW - Receptor-CD3 Complex, Antigen, T-Cell -- physiology KW - Flow Cytometry KW - Receptor-CD3 Complex, Antigen, T-Cell -- immunology KW - Antigens, CD28 -- immunology KW - Antigens, CD3 -- physiology KW - HIV-1 -- genetics KW - HIV-1 -- immunology KW - Gene Products, nef -- genetics KW - Gene Products, nef -- immunology KW - T-Lymphocytes -- virology KW - T-Lymphocytes -- immunology KW - Lymphocyte Activation -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69879804?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=HIV-1+Nef+increases+T+cell+activation+in+a+stimulus-dependent+manner.&rft.au=Schrager%2C+J+A%3BMarsh%2C+J+W&rft.aulast=Schrager&rft.aufirst=J&rft.date=1999-07-06&rft.volume=96&rft.issue=14&rft.spage=8167&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-26 N1 - Date created - 1999-08-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1997 Feb;71(2):1013-8 [8995620] J Virol. 1995 May;69(5):2977-88 [7707524] EMBO J. 1997 Feb 17;16(4):673-84 [9049297] J Virol. 1997 May;71(5):3776-87 [9094653] J Mol Med (Berl). 1997 Apr;75(4):249-58 [9151211] J Virol. 1997 Aug;71(8):6094-9 [9223503] Science. 1997 Aug 1;277(5326):693-6 [9235893] J Immunol. 1997 Oct 15;159(8):3823-37 [9378970] Science. 1997 Nov 14;278(5341):1291-5 [9360926] Science. 1997 Nov 14;278(5341):1295-300 [9360927] EMBO J. 1997 Dec 1;16(23):6964-76 [9384576] J Immunol. 1997 Dec 15;159(12):5921-30 [9550389] Cell. 1998 May 29;93(5):665-71 [9630210] Science. 1998 Sep 11;281(5383):1671-4 [9733513] Immunity. 1998 Nov;9(5):587-93 [9846480] J Virol. 1990 Sep;64(9):4093-8 [2384914] Genes Dev. 1990 Oct;4(10):1823-34 [2123468] Nature. 1991 Apr 11;350(6318):508-11 [2014052] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3972-6 [1902576] Cell. 1991 May 17;65(4):651-62 [2032289] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5326-30 [2052609] Virology. 1992 May;188(1):391-5 [1566581] AIDS Res Hum Retroviruses. 1992 May;8(5):545-51 [1355346] J Virol. 1992 Oct;66(10):6213-9 [1527859] J Virol. 1993 Mar;67(3):1511-6 [8437228] EMBO J. 1993 Feb;12(2):703-13 [8095017] Nature. 1993 Mar 25;362(6418):355-8 [8455722] Nature. 1993 Mar 25;362(6418):359-62 [8096068] J Immunol Methods. 1993 Apr 2;160(2):181-9 [8459105] J Virol. 1993 Aug;67(8):4639-50 [8043040] J Exp Med. 1994 Jan 1;179(1):101-13 [8270859] J Exp Med. 1994 Jan 1;179(1):115-23 [7903679] Cell. 1994 Mar 11;76(5):853-64 [8124721] J Immunol. 1994 May 15;152(10):5128-34 [8176229] J Virol. 1994 Jul;68(7):4177-85 [8207793] J Virol. 1994 Aug;68(8):5156-63 [8035515] Biochem Biophys Res Commun. 1994 Aug 30;203(1):498-505 [7915519] AIDS Res Hum Retroviruses. 1994 May;10(5):523-7 [7917514] EMBO J. 1994 Dec 1;13(23):5559-69 [7988553] J Virol. 1995 Mar;69(3):1842-50 [7853525] J Immunol. 1984 Jul;133(1):123-8 [6327821] Proc Natl Acad Sci U S A. 1987 Oct;84(19):6845-9 [3498942] Nature. 1987 Nov 19-25;330(6145):266-9 [3118220] Science. 1987 Dec 11;238(4833):1575-8 [2825351] Nature. 1988 Sep 29;335(6189):445-8 [2843775] J Virol. 1990 May;64(5):2421-5 [2157898] EMBO J. 1990 May;9(5):1551-60 [2184033] Virology. 1990 Jun;176(2):413-25 [2111956] J Virol. 1990 Jul;64(7):3391-8 [2191150] J Virol. 1995 Jul;69(7):4112-21 [7769669] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7739-43 [7644487] J Immunol. 1996 Jan 1;156(1):360-70 [8598486] J Biol Chem. 1996 Mar 8;271(10):5393-7 [8621393] J Virol. 1996 Jul;70(7):4283-90 [8676450] J Virol. 1996 Sep;70(9):6493-6 [8709288] Immunity. 1994 Aug;1(5):373-84 [7882168] Science. 1997 Mar 7;275(5305):1481-5 [9045614] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of hypertension on mortality in Pima Indians. AN - 69866510; 10393678 AB - The effect of hypertension on mortality was examined in 5284 Pima Indians, 1698 of whom had type 2 diabetes at baseline or developed it during follow-up. During a median follow-up of 12.2 years (range, 0.01 to 24.8 years), 470 nondiabetic subjects and 488 diabetic subjects died. In the nondiabetic subjects, 45 of the deaths were due to cardiovascular disease, 208 to other natural causes, and 217 to external causes; in the diabetic subjects, 106 of the deaths were due to cardiovascular disease, 85 to diabetic nephropathy, 226 to other natural causes, and 71 to external causes. In the nondiabetic subjects, after adjusting for age, sex, body mass index, and serum cholesterol concentration in a proportional hazards model, hypertension predicted death from cardiovascular disease (death rate ratio [DRR]=2.8; 95% CI, 1.4 to 5. 6; P=0.003). In the diabetic subjects, after additional adjustment for duration of diabetes, plasma glucose concentration, and proteinuria, hypertension strongly predicted deaths from diabetic nephropathy (DRR=3.5; 95% CI, 1.7 to 7.2; P<0.001), but it had little effect on deaths from cardiovascular disease (DRR=1.4; 95% CI, 0.88 to 2.3; P=0.15). We propose that the weak relationship between hypertension and cardiovascular disease in diabetic Pima Indians is not because of a diminished effect of hypertension on cardiovascular disease in diabetes, but because of a relatively greater effect of hypertension on the progression of diabetic nephropathy. Factors that may account for this finding in Pima Indians include a younger age at onset of type 2 diabetes, a low frequency of heavy smoking, favorable lipoprotein profiles and, possibly, enhanced susceptibility to renal disease. JF - Circulation AU - Sievers, M L AU - Bennett, P H AU - Roumain, J AU - Nelson, R G AD - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA. Y1 - 1999/07/06/ PY - 1999 DA - 1999 Jul 06 SP - 33 EP - 40 VL - 100 IS - 1 KW - Lipids KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Lipids -- blood KW - Neoplasms -- mortality KW - Humans KW - Disease Progression KW - Aged KW - Kidney Failure, Chronic -- etiology KW - Diabetes Mellitus, Type 2 -- mortality KW - Comorbidity KW - Cause of Death KW - Aged, 80 and over KW - Adult KW - Kidney Failure, Chronic -- mortality KW - Genetic Predisposition to Disease KW - Adolescent KW - Male KW - Arizona -- epidemiology KW - Alcoholism -- mortality KW - Body Mass Index KW - Cardiovascular Diseases -- mortality KW - Diabetic Nephropathies -- mortality KW - Cohort Studies KW - Incidence KW - Follow-Up Studies KW - Middle Aged KW - Female KW - Proportional Hazards Models KW - Prevalence KW - Mortality KW - Indians, North American KW - Hypertension -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69866510?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Circulation&rft.atitle=Effect+of+hypertension+on+mortality+in+Pima+Indians.&rft.au=Sievers%2C+M+L%3BBennett%2C+P+H%3BRoumain%2C+J%3BNelson%2C+R+G&rft.aulast=Sievers&rft.aufirst=M&rft.date=1999-07-06&rft.volume=100&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Circulation&rft.issn=1524-4539&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The zebrafish genome contains two distinct selenocysteine tRNA[Ser]sec genes. AN - 69894664; 10413087 AB - The zebrafish is widely used as a model system for studying mammalian developmental genetics and more recently, as a model system for carcinogenesis. Since there is mounting evidence that selenium can prevent cancer in mammals, including humans, we characterized the selenocysteine tRNA[Ser]sec gene and its product in zebrafish. Two genes for this tRNA were isolated and sequenced and were found to map at different loci within the zebrafish genome. The encoding sequences of both are identical and their flanking sequences are highly homologous for several hundred bases in both directions. The two genes likely arose from gene duplication which is a common phenomenon among many genes in this species. In addition, zebrafish tRNA[Ser]sec was isolated from the total tRNA population and shown to decode UGA in a ribosomal binding assay. JF - FEBS letters AU - Xu, X M AU - Zhou, X AU - Carlson, B A AU - Kim, L K AU - Huh, T L AU - Lee, B J AU - Hatfield, D L AD - Section on the Molecular Biology of Selenium, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/07/02/ PY - 1999 DA - 1999 Jul 02 SP - 16 EP - 20 VL - 454 IS - 1-2 SN - 0014-5793, 0014-5793 KW - RNA, Transfer, Amino Acyl KW - 0 KW - selenocysteinyl-tRNA KW - Index Medicus KW - Xenopus -- genetics KW - Animals KW - Genes, Duplicate KW - Base Sequence KW - Sequence Homology, Nucleic Acid KW - Models, Genetic KW - Molecular Sequence Data KW - Gene Library KW - RNA, Transfer, Amino Acyl -- genetics KW - Zebrafish -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69894664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEBS+letters&rft.atitle=The+zebrafish+genome+contains+two+distinct+selenocysteine+tRNA%5BSer%5Dsec+genes.&rft.au=Xu%2C+X+M%3BZhou%2C+X%3BCarlson%2C+B+A%3BKim%2C+L+K%3BHuh%2C+T+L%3BLee%2C+B+J%3BHatfield%2C+D+L&rft.aulast=Xu&rft.aufirst=X&rft.date=1999-07-02&rft.volume=454&rft.issue=1-2&rft.spage=16&rft.isbn=&rft.btitle=&rft.title=FEBS+letters&rft.issn=00145793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-09 N1 - Date created - 1999-08-09 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF135236; GENBANK; AF135237 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and molecular characterization of m3 muscarinic receptor dimers. AN - 69852268; 10383466 AB - Several studies suggest, but do not prove directly, that muscarinic receptors may be able to form dimeric or oligomeric arrays. To address this issue in a more direct fashion, we designed a series of biochemical experiments using a modified version of the rat m3 muscarinic receptor (referred to as m3') as a model system. When membrane lysates prepared from m3' receptor-expressing COS-7 cells were subjected to Western blot analysis under non-reducing conditions, several immunoreactive species were observed corresponding in size to putative receptor monomers, dimers, and oligomers. However, under reducing conditions, the monomeric receptor species represented the only detectable immunoreactive protein, consistent with the presence of disulfide-linked m3 receptor complexes. Similar results were obtained when native m3 muscarinic receptors present in rat brain membranes were analyzed. Control experiments carried out in the presence of high concentrations of the SH group alkylating agent, N-ethylmaleimide, suggested that disulfide bond formation did not occur artifactually during the preparation of cell lysates. The formation of m3' receptor dimers/multimers was confirmed in coimmunoprecipitation studies using differentially epitope-tagged m3' receptor constructs. In addition, these studies showed that m3' receptors were also able to form non-covalently associated receptor dimers and that m3' receptor dimer formation was receptor subtype-specific. Immunological studies also demonstrated that m3' receptor dimers/multimers were abundantly expressed on the cell surface. Site-directed mutagenesis studies indicated that two conserved extracellular Cys residues (Cys-140 and Cys-220) play key roles in the formation of disulfide-linked m3' receptor dimers. These results provide the first direct evidence for the existence of muscarinic receptor dimers and highlight the specificity and molecular diversity of G protein-coupled receptor dimerization/oligomerization. JF - The Journal of biological chemistry AU - Zeng, F Y AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07/02/ PY - 1999 DA - 1999 Jul 02 SP - 19487 EP - 19497 VL - 274 IS - 27 SN - 0021-9258, 0021-9258 KW - Muscarinic Agonists KW - 0 KW - Phosphatidylinositols KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Carbachol KW - 8Y164V895Y KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Animals KW - Phosphatidylinositols -- metabolism KW - Protein Structure, Secondary KW - COS Cells KW - Dimerization KW - Cysteine -- analysis KW - Amino Acid Sequence KW - Hydrolysis KW - Rats KW - Mutagenesis, Site-Directed KW - Muscarinic Agonists -- pharmacology KW - Molecular Sequence Data KW - Carbachol -- pharmacology KW - Receptors, Muscarinic -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69852268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+and+molecular+characterization+of+m3+muscarinic+receptor+dimers.&rft.au=Zeng%2C+F+Y%3BWess%2C+J&rft.aulast=Zeng&rft.aufirst=F&rft.date=1999-07-02&rft.volume=274&rft.issue=27&rft.spage=19487&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Concurrent chaperone and protease activities of ClpAP and the requirement for the N-terminal ClpA ATP binding site for chaperone activity. AN - 69851747; 10383442 AB - ClpA, a member of the Clp/Hsp100 family of ATPases, is both an ATP-dependent molecular chaperone and the regulatory component of ClpAP protease. We demonstrate that chaperone and protease activities occur concurrently in ClpAP complexes during a single round of RepA binding to ClpAP and ATP-dependent release. This result was substantiated with a ClpA mutant, ClpA(K220V), carrying an amino acid substitution in the N-terminal ATP binding site. ClpA(K220V) is unable to activate RepA, but the presence of ClpP or chemically inactivated ClpP restores its ability to activate RepA. The presence of ClpP simultaneously facilitates degradation of RepA. ClpP must remain bound to ClpA(K220V) for these effects, indicating that both chaperone and proteolytic activities of the mutant complex occur concurrently. ClpA(K220V) itself is able to form stable complexes with RepA in the presence of a poorly hydrolyzed ATP analog, adenosine 5'-O-(thiotriphosphate), and to release RepA upon exchange of adenosine 5'-O-(thiotriphosphate) with ATP. However, the released RepA is inactive in DNA binding, indicating that the N-terminal ATP binding site is essential for the chaperone activity of ClpA. Taken together, these results suggest that substrates bound to the complex of the proteolytic and ATPase components can be partitioned between release/reactivation and translocation/degradation. JF - The Journal of biological chemistry AU - Pak, M AU - Hoskins, J R AU - Singh, S K AU - Maurizi, M R AU - Wickner, S AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07/02/ PY - 1999 DA - 1999 Jul 02 SP - 19316 EP - 19322 VL - 274 IS - 27 SN - 0021-9258, 0021-9258 KW - DNA-Binding Proteins KW - 0 KW - Molecular Chaperones KW - Proteins KW - Trans-Activators KW - replication initiator protein KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Endopeptidases KW - EC 3.4.- KW - Serine Endopeptidases KW - EC 3.4.21.- KW - Endopeptidase Clp KW - EC 3.4.21.92 KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Models, Chemical KW - Proteins -- metabolism KW - Binding Sites KW - Serine Endopeptidases -- metabolism KW - Molecular Chaperones -- metabolism KW - Serine Endopeptidases -- genetics KW - Endopeptidases -- metabolism KW - Adenosine Triphosphate -- metabolism KW - Adenosine Triphosphatases -- metabolism KW - Adenosine Triphosphatases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69851747?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Concurrent+chaperone+and+protease+activities+of+ClpAP+and+the+requirement+for+the+N-terminal+ClpA+ATP+binding+site+for+chaperone+activity.&rft.au=Pak%2C+M%3BHoskins%2C+J+R%3BSingh%2C+S+K%3BMaurizi%2C+M+R%3BWickner%2C+S&rft.aulast=Pak&rft.aufirst=M&rft.date=1999-07-02&rft.volume=274&rft.issue=27&rft.spage=19316&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy. AN - 69815083; 10360821 AB - Gastric cancers are rarely diagnosed before the age of 40 years and the incidence reaches a peak during the 7th decade in the general population. A molecular mechanism of early tumor onset may be determined by comparing microsatellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients < or = 40 years of age and those of older ages. Three to 5 chromosomal loci, where MSI and/or LOH are commonly found in gastric cancers in the general population, were examined in formalin-fixed, paraffin-embedded samples from 102 patients < or = 40 years of age using a polymerase chain reaction-based non-radioactive screening method. MSI and/or LOH at a minimum of 1 locus were detected in 11/102 patients. The frequency of MSI and/or LOH at the D11S904 locus was significantly higher than that at the D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients. Among several clinicopathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared with tumors at the antrum and the corpus. Our findings suggest that a unique mechanism may be involved in increasing the susceptibility of the D11S904 locus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients < or = 40 years of age is associated with genetic changes at preferential chromosomal loci, including D11S904. JF - International journal of cancer AU - Shiao, Y H AU - Bovo, D AU - Guido, M AU - Capella, C AU - Cassaro, M AU - Busatto, G AU - Russo, V AU - Sidoni, A AU - Parenti, A R AU - Rugge, M AD - Laboratory of Comparative Carcinogenesis, NCI-FCRDC, National Institutes of Health, Frederick, MD, USA. Y1 - 1999/07/02/ PY - 1999 DA - 1999 Jul 02 SP - 59 EP - 62 VL - 82 IS - 1 SN - 0020-7136, 0020-7136 KW - Index Medicus KW - Humans KW - Adult KW - Adolescent KW - Male KW - Female KW - Stomach Neoplasms -- pathology KW - Microsatellite Repeats KW - Loss of Heterozygosity KW - Stomach Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69815083?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Microsatellite+instability+and%2For+loss+of+heterozygosity+in+young+gastric+cancer+patients+in+Italy.&rft.au=Shiao%2C+Y+H%3BBovo%2C+D%3BGuido%2C+M%3BCapella%2C+C%3BCassaro%2C+M%3BBusatto%2C+G%3BRusso%2C+V%3BSidoni%2C+A%3BParenti%2C+A+R%3BRugge%2C+M&rft.aulast=Shiao&rft.aufirst=Y&rft.date=1999-07-02&rft.volume=82&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-17 N1 - Date created - 1999-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An open trial of clozapine for dystonia. AN - 85307525; pmid-10435503 AB - Pharmacologic treatment of severe dystonia is often unsatisfactory. The atypical antipsychotic medication clozapine appears to improve tardive dystonia associated with conventional neuroleptic use. We studied the efficacy of clozapine for severe dystonia in five patients in an open trial. The patient cohort included four with generalized dystonia and one with Meige syndrome. All patients were evaluated at baseline and at least weekly while on medication with subjective assessment of response by the patient and physician rating using the Burke-Fahn-Marsden Evaluation Scale for Dystonia. All five subjects had significant improvement detected by the Burke-Fahn-Marsden Evaluation Scale as well as subjective improvement while on clozapine. Side effects, such as sedation and orthostatic hypotension, developed in all patients but was only treatment-limiting in one subject who developed persistent symptomatic orthostatic hypotension and tachycardia. Two of the four remaining patients continued clozapine after completion of the study; an additional patient was uncertain if the benefit outweighed the side effects. One patient discontinued treatment because of difficulty obtaining the FDA-required weekly white blood cell counts for patients on clozapine. We conclude that clozapine appears to be effective for generalized and refractory focal dystonia although its use may be limited by the side effects and need for hematologic monitoring. JF - Movement disorders : official journal of the Movement Disorder Society AU - Karp, B I AU - Goldstein, S R AU - Chen, R AU - Samii, A AU - Bara-Jimenez, W AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 652 EP - 657 VL - 14 IS - 4 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Analysis of Variance KW - Humans KW - Adult KW - Treatment Outcome KW - Aged KW - Middle Aged KW - Female KW - Male KW - Clozapine -- therapeutic use KW - GABA Antagonists -- therapeutic use KW - Dystonia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85307525?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=An+open+trial+of+clozapine+for+dystonia.&rft.au=Karp%2C+B+I%3BGoldstein%2C+S+R%3BChen%2C+R%3BSamii%2C+A%3BBara-Jimenez%2C+W%3BHallett%2C+M&rft.aulast=Karp&rft.aufirst=B&rft.date=1999-07-01&rft.volume=14&rft.issue=4&rft.spage=652&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Palatal tremor, progressive multiple cranial nerve palsies, and cerebellar ataxia: a case report and review of literature of palatal tremors in neurodegenerative disease. AN - 85306851; pmid-10435510 AB - We describe a patient with an unusual clinical presentation of progressive multiple cranial nerve palsies, cerebellar ataxia, and palatal tremor (PT) resulting from an unknown etiology. Magnetic resonance imaging showed evidence of hypertrophy of the inferior olivary nuclei, brain stem atrophy, and marked cerebellar atrophy. This combination of progressive multiple cranial nerve palsies, cerebellar ataxia, and PT has never been reported in the literature. We have also reviewed the literature of PT secondary to neurodegenerative causes. In a total of 23 patients, the common causes are sporadic olivopontocerebellar atrophy (OPCA; 22%), Alexander's disease (22%), unknown etiology (43.4%), and occasionally progressive supranuclear palsy (4.3%) and spinocerebellar degeneration (4.3%). Most patients present with progressive cerebellar ataxia and approximately two thirds of them have rhythmic tremors elsewhere. Ear clicks are observed in 13% and evidence of hypertrophy of the inferior olivary nucleus in 25% of the patients. The common neurodegenerative causes of PT are OPCA/multiple system atrophy, Alexander's disease, and, in most of them, the result of an unknown cause. JF - Movement disorders : official journal of the Movement Disorder Society AU - Kulkarni, P K AU - Muthane, U B AU - Taly, A B AU - Jayakumar, P N AU - Shetty, R AU - Swamy, H S AD - Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 689 EP - 693 VL - 14 IS - 4 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Cranial Nerve Diseases -- etiology KW - Myoclonus -- pathology KW - Cerebellar Ataxia -- etiology KW - Paralysis -- pathology KW - Cerebellar Ataxia -- pathology KW - Paralysis -- etiology KW - Brain -- pathology KW - Humans KW - Adult KW - Disease Progression KW - Myoclonus -- etiology KW - Cranial Nerve Diseases -- pathology KW - Male KW - Neurodegenerative Diseases -- physiopathology KW - Tremor -- pathology KW - Neurodegenerative Diseases -- pathology KW - Palatal Muscles -- innervation KW - Palate, Soft KW - Neurodegenerative Diseases -- complications KW - Tremor -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85306851?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Palatal+tremor%2C+progressive+multiple+cranial+nerve+palsies%2C+and+cerebellar+ataxia%3A+a+case+report+and+review+of+literature+of+palatal+tremors+in+neurodegenerative+disease.&rft.au=Kulkarni%2C+P+K%3BMuthane%2C+U+B%3BTaly%2C+A+B%3BJayakumar%2C+P+N%3BShetty%2C+R%3BSwamy%2C+H+S&rft.aulast=Kulkarni&rft.aufirst=P&rft.date=1999-07-01&rft.volume=14&rft.issue=4&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - SuppNotes - Comment in: Mov Disord. 2001 Jul;16(4):787 [11481720] N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Effects of physostigmine on swallowing and oral motor functions in patients with progressive supranuclear palsy: A pilot study. AN - 85301869; pmid-10341115 AB - The purpose of this pilot study was to investigate whether cholinergic stimulation reduces swallowing and oral motor disturbances in patients with progressive supranuclear palsy (PSP). A controlled, double-blind crossover trial of physostigmine, a centrally active cholinesterase inhibitor, and placebo was conducted. Patients were randomized to a 10-day crossover placebo-controlled double-blind trial of physostigmine at their previously determined best dose administered orally every 2 hr, six times per day. Patients were evaluated with ultrasound imaging of the oropharynx and an oral motor examination at baseline and during the third or fourth days of each study phase (placebo and drug). Under the double-blind placebo-controlled conditions, patients showed no statistically significant improvement in oral motor functions or swallow durations. Because patients with PSP have increased sensitivity to cholinergic blockade compared with control subjects, studies with newer, more potent cholinergic stimulating agents need further exploration. Suggestions for future research include the evaluation of newer direct cholinergic agonists in the treatment of the less-impaired PSP patients who may have a greater number of cholinergic neurons preserved and the evaluation of combined therapies. JF - Dysphagia AU - Frattali, C M AU - Sonies, B C AU - Chi-Fishman, G AU - Litvan, I AD - Speech-Language Pathology Section, Rehabilitation Medicine Department, W.G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 165 EP - 168 VL - 14 IS - 3 SN - 0179-051X, 0179-051X KW - Dentistry; Index Medicus KW - National Library of Medicine KW - Double-Blind Method KW - Humans KW - Cross-Over Studies KW - Middle Aged KW - Pilot Projects KW - Male KW - Female KW - Cholinesterase Inhibitors -- pharmacology KW - Supranuclear Palsy, Progressive -- complications KW - Physostigmine -- pharmacology KW - Cholinesterase Inhibitors -- therapeutic use KW - Deglutition Disorders -- drug therapy KW - Deglutition -- drug effects KW - Oropharynx -- drug effects KW - Physostigmine -- therapeutic use KW - Deglutition Disorders -- complications KW - Oropharynx -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85301869?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Dysphagia&rft.atitle=Effects+of+physostigmine+on+swallowing+and+oral+motor+functions+in+patients+with+progressive+supranuclear+palsy%3A+A+pilot+study.&rft.au=Frattali%2C+C+M%3BSonies%2C+B+C%3BChi-Fishman%2C+G%3BLitvan%2C+I&rft.aulast=Frattali&rft.aufirst=C&rft.date=1999-07-01&rft.volume=14&rft.issue=3&rft.spage=165&rft.isbn=&rft.btitle=&rft.title=Dysphagia&rft.issn=0179051X&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - National Institutes of Health, Warren Grant Magnuson Clinical Center. AN - 85301659; pmid-10420662 JF - ASHA AU - Frattali, C M AD - Speech-Language Pathology Section, W.G. Magnuson Clinical Center, NIH, USA. carol_frattali@nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 46 EP - 49 VL - 41 IS - 4 SN - 0001-2475, 0001-2475 KW - Index Medicus KW - National Library of Medicine KW - United States KW - Humans KW - Health Services -- supply & distribution KW - National Institutes of Health (U.S.) KW - Speech-Language Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85301659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=ASHA&rft.atitle=National+Institutes+of+Health%2C+Warren+Grant+Magnuson+Clinical+Center.&rft.au=Frattali%2C+C+M&rft.aulast=Frattali&rft.aufirst=C&rft.date=1999-07-01&rft.volume=41&rft.issue=4&rft.spage=46&rft.isbn=&rft.btitle=&rft.title=ASHA&rft.issn=00012475&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Small deletions in the type II collagen triple helix produce kniest dysplasia. AN - 85275095; pmid-10406661 AB - Kniest dysplasia is a moderately severe type II collagenopathy, characterized by short trunk and limbs, kyphoscoliosis, midface hypoplasia, severe myopia, and hearing loss. Mutations in the gene that encodes type II collagen (COL2A1), the predominant protein of cartilage, have been identified in a number of individuals with Kniest dysplasia. All but two of these previously described mutations cause in-frame deletions in type II collagen, either by small deletions in the gene or splice site alterations. Furthermore, all but one of these mutations is located between exons 12 and 24 in the COL2A1 gene. We used heteroduplex analysis to identify sequence anomalies in five individuals with Kniest dysplasia. Sequencing of the index patients' genomic DNA identified four new dominant mutations in COL2A1 that result in Kniest dysplasia: a 21-bp deletion in exon 16, an 18-bp deletion in exon 19, and 4-bp deletions in the splice donor sites of introns 14 and 20. A previously described 28-bp deletion at the COL2A1 exon 12-intron 12 junction, deleting the splice donor site, was identified in the fifth case. The latter three mutations are predicted to result in exon skipping in the mRNA encoded from the mutant allele. These data suggest that Kniest dysplasia results from shorter type II collagen monomers, and support the hypothesis that alteration of a specific COL2A1 domain, which may span from exons 12 to 24, leads to the Kniest dysplasia phenotype. JF - American Journal of Medical Genetics AU - Wilkin, D J AU - Artz, A S AU - South, S AU - Lachman, R S AU - Rimoin, D L AU - Wilcox, W R AU - McKusick, V A AU - Stratakis, C A AU - Francomano, C A AU - Cohn, D H AD - Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-1267, USA. PY - 1999 SP - 105 EP - 112 VL - 85 IS - 2 SN - 0148-7299, 0148-7299 KW - Bone and Bones KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Osteochondrodysplasias KW - Child KW - Child, Preschool KW - Collagen KW - Infant KW - Base Sequence KW - Models, Genetic KW - Molecular Sequence Data KW - Case Report KW - Male KW - Female KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85275095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Medical+Genetics&rft.atitle=Small+deletions+in+the+type+II+collagen+triple+helix+produce+kniest+dysplasia.&rft.au=Wilkin%2C+D+J%3BArtz%2C+A+S%3BSouth%2C+S%3BLachman%2C+R+S%3BRimoin%2C+D+L%3BWilcox%2C+W+R%3BMcKusick%2C+V+A%3BStratakis%2C+C+A%3BFrancomano%2C+C+A%3BCohn%2C+D+H&rft.aulast=Wilkin&rft.aufirst=D&rft.date=1999-07-01&rft.volume=85&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Medical+Genetics&rft.issn=01487299&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - What's the price of a research subject? Approaches to payment for research participation. AN - 85249642; pmid-10403861 JF - The New England Journal of Medicine AU - Dickert, N AU - Grady, C AD - National Institutes of Health, Bethesda, MD 20892, USA. PY - 1999 SP - 198 EP - 203 VL - 341 IS - 3 SN - 0028-4793, 0028-4793 KW - Researcher-Subject Relations KW - Vulnerable Populations KW - Human KW - Social Control, Formal KW - Clinical Trials KW - Comprehension KW - Federal Government KW - Therapeutic Human Experimentation KW - Nontherapeutic Human Experimentation KW - Persons KW - Risk Assessment KW - Human Experimentation KW - Ethics, Medical KW - Research KW - Models, Econometric KW - Research Subjects KW - Patient Selection UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85249642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=What%27s+the+price+of+a+research+subject%3F+Approaches+to+payment+for+research+participation.&rft.au=Dickert%2C+N%3BGrady%2C+C&rft.aulast=Dickert&rft.aufirst=N&rft.date=1999-07-01&rft.volume=341&rft.issue=3&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Representational abilities and the hearing status of child/mother dyads. AN - 85235418; pmid-10446723 AB - Two representational abilities, expressive and receptive language and symbolic play, were assessed in multiple formats in hearing and deaf 2-year-old children of hearing and deaf mothers. Based on maternal report, hearing children of hearing and deaf mothers produced more words than deaf children of hearing mothers, hearing children of hearing mothers more words than deaf children of deaf mothers, and deaf children of deaf mothers more words than deaf children of hearing mothers. Based on experimenter assessments, hearing children in both groups produced and comprehended more words than deaf children in both groups. By contrast, no differences emerged among these groups in child solitary symbolic play or in child-initiated or mother-initiated child collaborative symbolic play; all groups also increased equivalently in symbolic play between solitary and collaborative play. Representational language and symbolic play were unrelated in hearing children of hearing mothers and in deaf children of deaf mothers, but the 2 abilities were associated in children in the 2 child/mother mismatched hearing status groups. These findings are placed in the context of a proposed developing modularity of verbal and nonverbal symbol systems, and the implications of hearing status in communicative exchanges between children and their mothers in diverse hearing and deaf dyads are explored. JF - Child Development AU - Bornstein, M H AU - Selmi, A M AU - Haynes, O M AU - Painter, K M AU - Marx, E S AD - National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2030, USA. PY - 1999 SP - 833 EP - 852 VL - 70 IS - 4 SN - 0009-3920, 0009-3920 KW - Maternal Behavior KW - Questionnaires KW - Verbal Behavior KW - Mothers KW - Human KW - Sign Language KW - Cognition KW - Child, Preschool KW - Deafness KW - Nonverbal Communication KW - Comparative Study KW - Social Desirability KW - Adult KW - Middle Age KW - Child Language KW - Hearing KW - Male KW - Female KW - Mother-Child Relations KW - Language KW - Play and Playthings KW - Symbolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85235418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Representational+abilities+and+the+hearing+status+of+child%2Fmother+dyads.&rft.au=Bornstein%2C+M+H%3BSelmi%2C+A+M%3BHaynes%2C+O+M%3BPainter%2C+K+M%3BMarx%2C+E+S&rft.aulast=Bornstein&rft.aufirst=M&rft.date=1999-07-01&rft.volume=70&rft.issue=4&rft.spage=833&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. AN - 85233236; pmid-10448192 AB - Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning. JF - Brain Research AU - Crawley, J N AD - Section on Behavioral Neuropharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Building 10, Room 4D11, Bethesda, MD 20892-1375, USA. PY - 1999 SP - 18 EP - 26 VL - 835 IS - 1 SN - 0006-8993, 0006-8993 KW - Phenotype KW - Human KW - Animal KW - Health KW - Mice KW - Psychomotor Performance KW - Mice, Transgenic KW - Research Design KW - Sensation KW - Behavior, Animal KW - Mice, Knockout UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85233236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+Research&rft.atitle=Behavioral+phenotyping+of+transgenic+and+knockout+mice%3A+experimental+design+and+evaluation+of+general+health%2C+sensory+functions%2C+motor+abilities%2C+and+specific+behavioral+tests.&rft.au=Crawley%2C+J+N&rft.aulast=Crawley&rft.aufirst=J&rft.date=1999-07-01&rft.volume=835&rft.issue=1&rft.spage=18&rft.isbn=&rft.btitle=&rft.title=Brain+Research&rft.issn=00068993&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - The Association Between Severe Nephropathy and Pheochromocytoma in the Male F344 Rat-- The National Toxicology Program Experience AN - 754892465; 13490759 AB - The possible correlation between the severity of chronic progressive glomerulonephropathy (CPN) and the incidence of adrenal pheochromocytoma was examined in selected studies of male Fischer 344 (F344) rats at the National Toxicology Program (NTP). The NTP historical control database was first examined in order to determine whether there was association between the severity of CPN and the occurrence of adrenal pheochromocytoma in unexposed animals. Following this analysis, the 125 most recent NTP studies conducted in F344 rats were examined in order to determine how frequently chemicals that cause increased severity of CPN showed an increased incidence of pheochromocytoma. Finally, we examined the association between the incidence of pheochromocytoma and the severity of CPN in those NTP studies with chemically related increased rates of pheochromocytoma. In control male F344 rats surviving beyond 21 mo, the incidence of adrenal pheochromocytoma was consistently higher in animals with more severe CPN. This association was significant (p < 0.05) both for 900 NTP inhalation study controls and 900 NTP feeding study controls. An association was not consistently observed when dosed groups were considered. Although 22% (28/125) of NTP studies reported a chemically related increased severity of CPN, only 3 of these reported a corresponding significant increase in the incidence of pheochromocytoma. Of 6 NTP studies that reported increased incidence of pheochromocytoma, animals with pheochromocytoma from 5 of those studies had some degree of increased severity of CPN. However, the estimated strength of the correlation with the severity of CPN varied from study to study and was often quite different from that indicated by an analysis of the more extensive NTP control databases. The possible correlation between the severity of CPN and the incidence of pheochromocytoma may influence interpretation of carcinogenic effects observed at this site. JF - Toxicologic Pathology AU - Nyska, Abraham AU - Haseman, Joseph K AU - Hailey, James R AU - Smetana, Samuel AU - Maronpot, Robert R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA, Nyska@niehs.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 456 EP - 462 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 27 IS - 4 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts KW - Rat adrenal medullary tumors KW - glomerulonephropathy KW - calcium KW - nongenotoxic KW - carcinogenicity KW - Inhalation KW - Databases KW - Computer programs KW - Feeding KW - Nephropathy KW - Pheochromocytoma KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/754892465?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=The+Association+Between+Severe+Nephropathy+and+Pheochromocytoma+in+the+Male+F344+Rat--+The+National+Toxicology+Program+Experience&rft.au=Nyska%2C+Abraham%3BHaseman%2C+Joseph+K%3BHailey%2C+James+R%3BSmetana%2C+Samuel%3BMaronpot%2C+Robert+R&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=1999-07-01&rft.volume=27&rft.issue=4&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339902700410 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Inhalation; Feeding; Computer programs; Databases; Nephropathy; Pheochromocytoma DO - http://dx.doi.org/10.1177/019262339902700410 ER - TY - JOUR T1 - COX-2 inhibitors--IBC conference. 12-13 April 1999, Coronado, CA, USA. AN - 70854424; 16127636 AB - The introduction of celecoxib (Celebrex, Figure 1; GD Searle and Co) as the first cyclooxygenase (COX)2 selective inhibitor in the US and the expected introduction of rofecoxib (Vioxx; Merck and Co Inc) as the first COX2 inhibitor with an acute pain indication, has prompted interest in this class of drugs as a possible therapeutic improvement on dual COX1/COX2 inhibitor NSAIDs, currently on the market. Recognition that the COX-2 enzyme may have a broader role than pain and inflammation has led to studies investigating the efficacy of COX-2 inhibitors for Alzheimer's disease (AD), stroke, cardiovascular disease and colon cancer. Speakers at the second annual conference sponsored by IBC, addressed issues ranging from the basic concepts of COX2 specificity versus selectivity, pathways and regulatory factors related to COX2 expression, the principles underlying the possible broad implications of the COX2 mechanisms, as well as summaries of recently completed clinical trials supporting the clinical efficacy and safety of COX2 inhibitors in humans. The timeliness of this meeting is emphasized by the recent approval of rofecoxib by the FDA Arthritis Advisory panel and the initial reports in the media of toxicity attributed to celecoxib. Preclinical and limited clinical data presented suggest possible therapeutic roles for selective COX2 inhibitors in neurodegeneration due to both AD and stroke, the prevention and treatment of colon cancer, prevention of premature labor, as well as pain and inflammation. JF - IDrugs : the investigational drugs journal AU - Dionne, R AD - dionne@yoda.nidr.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 664 EP - 666 VL - 2 IS - 7 SN - 1369-7056, 1369-7056 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70854424?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IDrugs+%3A+the+investigational+drugs+journal&rft.atitle=COX-2+inhibitors--IBC+conference.+12-13+April+1999%2C+Coronado%2C+CA%2C+USA.&rft.au=Dionne%2C+R&rft.aulast=Dionne&rft.aufirst=R&rft.date=1999-07-01&rft.volume=2&rft.issue=7&rft.spage=664&rft.isbn=&rft.btitle=&rft.title=IDrugs+%3A+the+investigational+drugs+journal&rft.issn=13697056&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2005-10-13 N1 - Date created - 2005-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection. AN - 70036022; 10483047 AB - Depression represents a major public health problem. It is estimated that 13-20% of the population has some depressive symptoms at any given time and about 5% of the population is assumed to suffer from major depression. Known pathological processes include ischemia, neoplasia, necrosis, apoptosis, infection, and inflammation. Of those, inflammation is the most compatible with the waxing and waning course of depression, and could explain the biology of this disorder that has a fluctuating course with severe episodes that can be followed by partial or complete remission. Over the years a body of evidence has been accumulated suggesting that major depression is associated with dysfunction of inflammatory mediators. Major depression commonly co-occurs with ischemic heart disease and decreased bone mineral density. Depressive symptoms are known to have a negative impact on cardiovascular prognosis, increasing the mortality rate of coronary artery disease. Several lines of evidence indicate that brain cytokines, principally interleukin-1beta (IL-1beta) and IL-1 receptor antagonist may have a role in the biology of major depression, and that they might additionally be involved in the pathophysiology and somatic consequences of depression as well as in the effects of antidepressant treatment. A particularly unique and novel aspect of the studies and views discussed here is their potential to lead to interventions which may reduce the morbidity and mortality risks for osteoporosis, cardiovascular disease, and behavioral symptoms in patients with major depression. We also discuss the emerging concept of peripheral and central cytokine compartments: their integration and differential regulation is a key element for the optimal functioning of the immune and nervous systems. JF - Molecular psychiatry AU - Licinio, J AU - Wong, M L AD - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. licinio@nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 317 EP - 327 VL - 4 IS - 4 SN - 1359-4184, 1359-4184 KW - Cytokines KW - 0 KW - Neuroprotective Agents KW - Neurotoxins KW - Index Medicus KW - Animals KW - Inflammation -- physiopathology KW - Humans KW - Neurotoxins -- toxicity KW - Neuroprotective Agents -- pharmacology KW - Brain -- physiopathology KW - Stress, Psychological -- immunology KW - Cytokines -- genetics KW - Depressive Disorder -- immunology KW - Stress, Psychological -- physiopathology KW - Depressive Disorder -- physiopathology KW - Cytokines -- physiology KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70036022?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+psychiatry&rft.atitle=The+role+of+inflammatory+mediators+in+the+biology+of+major+depression%3A+central+nervous+system+cytokines+modulate+the+biological+substrate+of+depressive+symptoms%2C+regulate+stress-responsive+systems%2C+and+contribute+to+neurotoxicity+and+neuroprotection.&rft.au=Licinio%2C+J%3BWong%2C+M+L&rft.aulast=Licinio&rft.aufirst=J&rft.date=1999-07-01&rft.volume=4&rft.issue=4&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Molecular+psychiatry&rft.issn=13594184&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-18 N1 - Date created - 1999-10-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Thrombocytopenia after isolated limb or hepatic perfusions with melphalan: the risk of heparin-induced thrombocytopenia. AN - 69990153; 10458686 AB - Three cases of heparin-induced thrombocytopenia (HIT) were observed in patients undergoing isolated limb perfusion (ILP) with melphalan. This occurrence prompted the discontinuation of prophylactic postoperative heparin in ILP patients and its avoidance in patients undergoing isolated hepatic perfusion (IHP). The need to reassess these decisions led to a review of thrombocytopenia in both patient populations. Records of all patients treated with ILP or IHP at our institution from July 1992 through November 1996, were reviewed. Nine IHP patients were tested prospectively for heparin-related antibodies using serum samples obtained perioperatively and during the second postoperative week. Thrombocytopenia (< 100,000 platelets/microL) developed postoperatively in 30% of 131 ILP patients and in 77% of 56 IHP patients. No cases of HIT were identified other than the three who had been previously diagnosed. The prevalence of HIT in heparinized ILP patients was 2.8% (3/108). All nine IHP patients developed heparin-related antibodies postoperatively. Because the prevalence of HIT following ILP is in the range observed in other clinical settings, postoperative heparin prophylaxis is an option. However, it probably should be limited to the first week, and daily platelet counts should be reviewed for a pattern of thrombocytopenia consistent with HIT. The prevalence of heparin-related antibodies after IHP is so high that prophylactic heparin should be avoided in this setting. JF - Annals of surgical oncology AU - Masucci, I P AU - Calis, K A AU - Bartlett, D L AU - Alexander, H R AU - Horne, M K AD - Pharmacy Department of the Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1999 SP - 476 EP - 480 VL - 6 IS - 5 SN - 1068-9265, 1068-9265 KW - Antibodies KW - 0 KW - Anticoagulants KW - Antineoplastic Agents, Alkylating KW - Heparin KW - 9005-49-6 KW - Melphalan KW - Q41OR9510P KW - Index Medicus KW - Postoperative Complications -- chemically induced KW - Medical Records KW - Prospective Studies KW - Antibodies -- blood KW - Risk Factors KW - Humans KW - Adult KW - Retrospective Studies KW - Enzyme-Linked Immunosorbent Assay KW - Melphalan -- administration & dosage KW - Chemotherapy, Cancer, Regional Perfusion KW - Anticoagulants -- adverse effects KW - Thrombocytopenia -- chemically induced KW - Antineoplastic Agents, Alkylating -- administration & dosage KW - Heparin -- immunology KW - Anticoagulants -- immunology KW - Heparin -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69990153?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+surgical+oncology&rft.atitle=Thrombocytopenia+after+isolated+limb+or+hepatic+perfusions+with+melphalan%3A+the+risk+of+heparin-induced+thrombocytopenia.&rft.au=Masucci%2C+I+P%3BCalis%2C+K+A%3BBartlett%2C+D+L%3BAlexander%2C+H+R%3BHorne%2C+M+K&rft.aulast=Masucci&rft.aufirst=I&rft.date=1999-07-01&rft.volume=6&rft.issue=5&rft.spage=476&rft.isbn=&rft.btitle=&rft.title=Annals+of+surgical+oncology&rft.issn=10689265&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-02 N1 - Date created - 1999-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Assessment of all-trans retinoic acid (ATRA) efficacy as a single agent in primary lymphoid neoplasia. AN - 69978712; 10456660 AB - All-trans retinoic acid (ATRA) is currently widely used in the therapy of acute promyelocytic leukemia and is being tested in vitro and in vivo on several other malignancies. Previously ATRA has been shown to inhibit the growth in vitro, of established human myeloma cell lines as well as cultured primary myeloma cells from patients. ATRA acts by down-regulating IL-6-receptor-alpha or gp130 on the surface of the myeloma cells. However, despite its in vitro effects on myeloma cells, ATRA therapy on advanced stage multiple myeloma (MM) patients has so far largely been ineffective. In current studies, we have assessed the efficacy of ATRA therapy against primary murine plasma cell tumors, which are an animal model for human MM. These tumors are induced at about 50% incidence in pristane-primed BALB/c mice by injection of v-raf/v-myc- containing retroviruses and are IL-6 dependent. Using this animal model, we assessed the effect of ATRA as a therapeutic agent against primary tumors at two early time points in disease development. ATRA was administered in liposomal vesicles (ATRAGEN), since liposomal-ATRA has been shown to circumvent clearance mechanisms by hepatic microsomes, which normally occur with free ATRA. In addition, ATRAGEN was previously shown to be less toxic in mice than free ATRA. ATRAGEN was administered beginning on day 25 or day 45 after virus injection and continued twice weekly for 8-11 weeks. ATRAGEN administration begun at either time point did not alter the incidence or the latency of plasma cell tumors compared with control animals. These results suggest that ATRA may not be an effective sole therapy against early MM. JF - Medical oncology (Northwood, London, England) AU - Swaminathan, N AU - Lopez-Berestein, G AU - Rudikoff, S AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 119 EP - 128 VL - 16 IS - 2 SN - 1357-0560, 1357-0560 KW - Antineoplastic Agents KW - 0 KW - Liposomes KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Tretinoin KW - 5688UTC01R KW - Index Medicus KW - Neoplasm Transplantation KW - Animals KW - Blotting, Southern KW - Mice KW - Flow Cytometry KW - Cell Line, Transformed KW - Mice, Inbred BALB C KW - Female KW - Plasmacytoma -- drug therapy KW - Antineoplastic Agents -- therapeutic use KW - Tretinoin -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69978712?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.atitle=Assessment+of+all-trans+retinoic+acid+%28ATRA%29+efficacy+as+a+single+agent+in+primary+lymphoid+neoplasia.&rft.au=Swaminathan%2C+N%3BLopez-Berestein%2C+G%3BRudikoff%2C+S&rft.aulast=Swaminathan&rft.aufirst=N&rft.date=1999-07-01&rft.volume=16&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Medical+oncology+%28Northwood%2C+London%2C+England%29&rft.issn=13570560&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lycanthropy in depression: two case reports. AN - 69975159; 10364724 AB - Two cases of lycanthropy presenting as part of a depressive disorder are described. The patients responded favorably to pharmacotherapy. In both cases, a positive history of dog bite influenced the presentation of symptoms. The authors speculate whether the defense of identification with the aggressor was operative. JF - Psychopathology AU - Rao, K AU - Gangadhar, B N AU - Janakiramiah, N AD - National Institute of Mental Health and Neurosciences, Bangalore, India. kiran@nimhans.ren.nic.in PY - 1999 SP - 169 EP - 172 VL - 32 IS - 4 SN - 0254-4962, 0254-4962 KW - Index Medicus KW - Animals KW - Diagnosis, Differential KW - Drug Therapy KW - Humans KW - Adult KW - Dogs KW - Aggression KW - Adolescent KW - Male KW - Depression -- psychology KW - Body Image KW - Depression -- drug therapy KW - Depression -- diagnosis KW - Bites and Stings -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69975159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopathology&rft.atitle=Lycanthropy+in+depression%3A+two+case+reports.&rft.au=Rao%2C+K%3BGangadhar%2C+B+N%3BJanakiramiah%2C+N&rft.aulast=Rao&rft.aufirst=K&rft.date=1999-07-01&rft.volume=32&rft.issue=4&rft.spage=169&rft.isbn=&rft.btitle=&rft.title=Psychopathology&rft.issn=02544962&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-08 N1 - Date created - 1999-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of adaptive responses following exposure to ionizing radiation. AN - 69969268; 10454071 JF - Human & experimental toxicology AU - Feinendegen, L E AD - Department of Nuclear Medicine, Clinical Center National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 426 EP - 432 VL - 18 IS - 7 SN - 0960-3271, 0960-3271 KW - Index Medicus KW - Animals KW - Humans KW - Environmental Exposure KW - Dose-Response Relationship, Radiation KW - Adaptation, Physiological -- radiation effects KW - Radiation Tolerance -- radiation effects KW - Adaptation, Physiological -- physiology KW - Radiation Tolerance -- physiology KW - Radiation, Ionizing UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69969268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+%26+experimental+toxicology&rft.atitle=The+role+of+adaptive+responses+following+exposure+to+ionizing+radiation.&rft.au=Feinendegen%2C+L+E&rft.aulast=Feinendegen&rft.aufirst=L&rft.date=1999-07-01&rft.volume=18&rft.issue=7&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Human+%26+experimental+toxicology&rft.issn=09603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-17 N1 - Date created - 1999-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutamate and antimitotic agents induce differentiation, p53 activation, and apoptosis in rodent neostriatal cell lines immortalized with the tsA58 allele of SV40 large T antigen. AN - 69964539; 10448422 AB - The tsA58 allele of SV40 large T antigen has the ability to immortalize cells, which is thought to be due, in part, to binding of p53 protein by T antigen at 33 degrees C. At the nonpermissive temperature (39.5 degrees C), it is thought that p53 is released, inducing growth arrest, vulnerability to apoptosis, and loss of the immortal phenotype. In cell lines derived from the rat neostriatum immortalized with tsA58, the toxic agents Adriamycin, cytosine arabinoside, and glutamate induced apoptosis and increased p53 activity and differentiation. The apoptosis and p53-inducing effects of the drugs were not greater at 39.5 degrees C compared to 33 degrees C, suggesting that p53 is not effectively blocked even at 33 degrees C. Growth arrest was not induced under most treatment conditions despite p53 induction. On the other hand, process extension was enhanced at 39.5 degrees C compared to 33 degrees C. Therefore, these cell lines are temperature sensitive with respect to differentiation, but not growth regulation or apoptosis. JF - Experimental neurology AU - Conejero, C AU - Wright, R AU - Freed, W AD - National Institute on Drug Abuse, Cellular Neurobiology Branch, Baltimore, Maryland 21224, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 109 EP - 120 VL - 158 IS - 1 SN - 0014-4886, 0014-4886 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Antineoplastic Agents KW - Tumor Suppressor Protein p53 KW - Cytarabine KW - 04079A1RDZ KW - Glutamic Acid KW - 3KX376GY7L KW - Doxorubicin KW - 80168379AG KW - Index Medicus KW - Rats KW - Animals KW - Alleles KW - Retinal Neoplasms -- ultrastructure KW - Cell Line, Transformed -- drug effects KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Binding Sites -- drug effects KW - Cell Movement -- drug effects KW - Cell Division -- drug effects KW - Neuroblastoma -- ultrastructure KW - Cell Differentiation -- drug effects KW - Cytarabine -- pharmacology KW - Doxorubicin -- pharmacology KW - Neostriatum -- ultrastructure KW - Tumor Suppressor Protein p53 -- drug effects KW - Neostriatum -- drug effects KW - Apoptosis -- drug effects KW - Antigens, Polyomavirus Transforming -- genetics KW - Glutamic Acid -- pharmacology KW - Antineoplastic Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69964539?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+neurology&rft.atitle=Glutamate+and+antimitotic+agents+induce+differentiation%2C+p53+activation%2C+and+apoptosis+in+rodent+neostriatal+cell+lines+immortalized+with+the+tsA58+allele+of+SV40+large+T+antigen.&rft.au=Conejero%2C+C%3BWright%2C+R%3BFreed%2C+W&rft.aulast=Conejero&rft.aufirst=C&rft.date=1999-07-01&rft.volume=158&rft.issue=1&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Experimental+neurology&rft.issn=00144886&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Coupling efficiency of brain beta-adrenergic receptors to Gs protein in suicide, alcoholism and control subjects. AN - 69960537; 10445370 AB - Abnormal beta-adrenergic receptor (betaAR) density in the brains of suicide victims has been reported, although results of studies are inconsistent. Ethanol modifies betaAR-mediated signal transduction. Moreover abnormal betaAR function has been implicated in alcoholism. BetaAR antagonists, which were used as ligands in previous betaAR binding studies, also bind to 5-HT1B/1Dbeta receptors; hence, their estimates of betaAR density are confounded by binding to 5-HT1B/1Dbeta receptors. More importantly, previous studies did not examine betaAR agonist affinity or coupling efficiency to Gs protein. We investigated agonist affinity and coupling efficiency of betaAR to Gs protein in the brains of ten suicide victims, six subjects with alcoholism, and eight controls. There were no differences in betaAR density in either the frontal cortex or hippocampus of suicide victims or alcoholic subjects compared to controls. Preliminary results indicate betaAR supercoupling in suicide victims in both brain regions and uncoupling in alcoholic subjects in the frontal cortex. These results are discussed in view of the existing literature on the role of betaAR in suicide and alcoholism and the mechanism of action of antidepressants. JF - Psychopharmacology AU - Gurguis, G N AU - Turkka, J AU - Laruelle, M AU - Kleinman, J AU - Linnoila, M AD - Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892-1256, USA. gurguis.george@dallas.va.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 31 EP - 38 VL - 145 IS - 1 SN - 0033-3158, 0033-3158 KW - Adrenergic beta-Antagonists KW - 0 KW - Receptors, Adrenergic, beta KW - Iodocyanopindolol KW - 83498-72-0 KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Index Medicus KW - Adrenergic beta-Antagonists -- analysis KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Iodocyanopindolol -- analysis KW - Male KW - Female KW - Receptors, Adrenergic, beta -- metabolism KW - Receptors, Adrenergic, beta -- analysis KW - Cerebral Cortex -- chemistry KW - Cerebral Cortex -- metabolism KW - Hippocampus -- metabolism KW - Suicide KW - Alcoholism -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- analysis KW - GTP-Binding Protein alpha Subunits, Gs -- metabolism KW - Hippocampus -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69960537?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Coupling+efficiency+of+brain+beta-adrenergic+receptors+to+Gs+protein+in+suicide%2C+alcoholism+and+control+subjects.&rft.au=Gurguis%2C+G+N%3BTurkka%2C+J%3BLaruelle%2C+M%3BKleinman%2C+J%3BLinnoila%2C+M&rft.aulast=Gurguis&rft.aufirst=G&rft.date=1999-07-01&rft.volume=145&rft.issue=1&rft.spage=31&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-14 N1 - Date created - 1999-09-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of CYP1A2 in the toxicity of long-term phenacetin feeding in mice. AN - 69959691; 10445756 AB - The mechanisms underlying phenacetin-induced toxicity and carcinogenicity are not clear. In particular, it is not known whether these effects are mediated by metabolic activation of the drug. CYP1A2 is known to metabolize phenacetin in vitro. To determine the role of this enzyme in vivo, the toxicity and carcinogenicity of phenacetin was examined in Cyp1a2-null mice (that lack CYP1A2). Six- to 8-week-old wild type (+/+) or null (-/-) mice were fed either a control diet, or one containing 1.25% phenacetin, ad libitum for up to 67 weeks. Representative groups of mice were examined for phenacetin-induced toxicity and carcinogenicity after 36, 48, 58, or 67 weeks of feeding. Consistent with the known role of CYP1A2 in phenacetin metabolism, plasma levels of phenacetin were higher and acetaminophen levels lower in the (-/-) mice fed phenacetin compared to phenacetin-fed (+/+) controls. Weight gain was significantly depressed in both groups of phenacetin-fed mice after 4 weeks of feeding, and continued to be lower for the remainder of the experiment, compared to controls. Hepatomegaly and splenomegaly were more severe in (-/-) mice but present in both genotypes fed phenacetin at all time points assessed. Histological analysis of liver, kidney, spleen, and urogenital tract also revealed a differential response in the (-/-) mice fed phenacetin compared to (+/+) mice fed the same diet. Further, mortality was the most severe in the (-/-) mice fed phenacetin than in all other groups. Despite significant toxicity in (-/-) mice fed phenacetin, only one renal carcinoma was found among them. Results from this work demonstrate that, in the absence of CYP1A2, phenacetin is more toxic than in controls. This provides evidence that metabolism of phenacetin by CYP1A2 alters toxicity in vivo, and suggests that alternate CYP1A2-independent metabolic pathways contribute to its toxicity. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Peters, J M AU - Morishima, H AU - Ward, J M AU - Coakley, C J AU - Kimura, S AU - Gonzalez, F J AD - Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. jpeters@helix.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 82 EP - 89 VL - 50 IS - 1 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Cytochrome P-450 CYP1A2 KW - EC 1.14.14.1 KW - Phenacetin KW - ER0CTH01H9 KW - Index Medicus KW - Urinary Bladder -- pathology KW - Animals KW - Survival Rate KW - Kidney Neoplasms -- chemically induced KW - Mice KW - Time Factors KW - Male KW - Female KW - Urinary Bladder -- drug effects KW - Organ Size -- drug effects KW - Carcinoma -- chemically induced KW - Cytochrome P-450 CYP1A2 -- physiology KW - Acetaminophen -- blood KW - Phenacetin -- administration & dosage KW - Carcinogens -- toxicity KW - Phenacetin -- toxicity KW - Phenacetin -- blood KW - Acetaminophen -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69959691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Role+of+CYP1A2+in+the+toxicity+of+long-term+phenacetin+feeding+in+mice.&rft.au=Peters%2C+J+M%3BMorishima%2C+H%3BWard%2C+J+M%3BCoakley%2C+C+J%3BKimura%2C+S%3BGonzalez%2C+F+J&rft.aulast=Peters&rft.aufirst=J&rft.date=1999-07-01&rft.volume=50&rft.issue=1&rft.spage=82&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-19 N1 - Date created - 1999-10-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Higher activity of 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) coincides with lower background levels of 8-oxo-2'-deoxyguanosine in DNA of fetal compared with maternal mouse organs. AN - 69950800; 10443924 AB - Mammalian homologues of Escherichia coli MutT, a protein having 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase (8-oxo-dGTPase) activity, are thought to play the same role in preventing the incorporation of promutagenic 8-oxo-2'-deoxyguanosine (8-oxo-dG) into DNA. One could thus expect that higher activity of 8-oxo-dGTPase should correlate with a lower background level of 8-oxo-dG in nuclear DNA. During transplacental carcinogenesis experiments, in control healthy Swiss mice on day 18 of gestation we found consistently lower levels of 8-oxo-dG in DNA in fetal livers and lungs (1.74+/-0.04 SE and 1.49+/-0.08 SE 8-oxo-dG/10(5) dG, respectively; pooled organs of fetuses of 8 dams) as compared with maternal organs (3.05+/-0.20 SE and 3.08+/-0.17 SE 8-oxo-dG/10(5) dG, respectively; n = 8). The 8-oxo-dGTPase activity determination in the same organs revealed that the lower levels of 8-oxo-dG in fetal DNA did, indeed, coincide with higher 8-oxo-dGTPase activity (48.8+/-2.6 SE and 52.5+/-2.5 SE U/mg protein in livers and lungs, respectively); and vice versa, higher 8-oxo-dG levels in DNA of maternal organs were associated with lower levels of 8-oxo-dGTPase activity (24.3+/-1.3 SE and 4.7+/-0.6 SE U/mg protein, as above). Without excluding other reasons for the relatively low 8-oxo-dG background in DNA of fetal tissues (e.g., higher level of antioxidants and antioxidative enzymes; more efficient DNA repair), this inverse relationship may support or at least does not contradict the concept of a guardian role of 8-oxo-dGTPase against 8-oxo-dGTP mutagenicity in mammalian cells. JF - Free radical biology & medicine AU - Bialkowski, K AU - Bialkowska, A AU - Anderson, L M AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, SAIC Frederick, MD 21702-1201, USA. karolb@mail.ncifcrf.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 90 EP - 94 VL - 27 IS - 1-2 SN - 0891-5849, 0891-5849 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - DNA KW - 9007-49-2 KW - Phosphoric Monoester Hydrolases KW - EC 3.1.3.2 KW - 8-oxodGTPase KW - EC 3.6.1.55 KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Animals KW - DNA -- metabolism KW - Lung -- embryology KW - Liver -- metabolism KW - Mice KW - Lung -- metabolism KW - Male KW - Liver -- embryology KW - Female KW - Deoxyguanosine -- metabolism KW - Phosphoric Monoester Hydrolases -- metabolism KW - Fetus -- metabolism KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69950800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=Higher+activity+of+8-oxo-2%27-deoxyguanosine+5%27-triphosphate+pyrophosphohydrolase+%288-oxo-dGTPase%29+coincides+with+lower+background+levels+of+8-oxo-2%27-deoxyguanosine+in+DNA+of+fetal+compared+with+maternal+mouse+organs.&rft.au=Bialkowski%2C+K%3BBialkowska%2C+A%3BAnderson%2C+L+M%3BKasprzak%2C+K+S&rft.aulast=Bialkowski&rft.aufirst=K&rft.date=1999-07-01&rft.volume=27&rft.issue=1-2&rft.spage=90&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-12 N1 - Date created - 1999-11-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of retinoic acid and 8-chloro-adenosine 3',5'-cyclic monophosphate on the regulation of retinoic acid receptor beta and apoptosis: involvement of mitochondria. AN - 69928398; 10430097 AB - In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective, even at doses that are toxic to the host. In late stages of breast cancer, patients do not respond to RA because the expression of RA receptor beta (RARbeta) is lost. In the present study, the intracellular mechanism(s) of synergistic effects of RA and a site-selective cyclic AMP (cAMP) analogue, 8-chloro-adenosine 3',5'-cyclic monophosphate (8-Cl-cAMP), on growth inhibition and apoptosis in breast cancer cells was examined. Our data demonstrated that hormone-dependent MCF-7 cells, but not hormone-independent MDA-MB-231 cells, are sensitive to RA-induced growth inhibition and apoptosis. Introduction of the RARbeta gene into MDA-MB-231 cells resulted in a gain of RA sensitivity. 8-Cl-cAMP acted synergistically with all-trans-RA in inducing and activating RARbeta gene expression that correlates with the reduction in mitochondrial membrane potential, redistribution of cytochrome c, activation of caspases, cleavage of poly(ADP-ribose) polymerase and DNA-dependent protein kinase (catalytic subunit), and induction of apoptosis. Mutations in the cAMP response element-related motif within the RARbeta promoter resulted in loss of synergy in RARbeta transcription. In addition, inhibition of RARbeta expression by an antisense construct also blocked the antitumor effects of RA + 8-Cl-cAMP. Thus, RARbeta can mediate RA and/or cAMP action in breast cancer cells by promoting apoptosis. Therefore, loss of RARbeta expression may contribute to the tumorigenicity of human mammary epithelial cells. These findings suggest that RA and 8-Cl-cAMP act in a synergistic fashion and may have potential for combination biotherapy for the treatment of malignant diseases. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Srivastava, R K AU - Srivastava, A R AU - Cho-Chung, Y S AU - Longo, D L AD - Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, Maryland 21224-6825, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1892 EP - 1904 VL - 5 IS - 7 SN - 1078-0432, 1078-0432 KW - Antineoplastic Agents KW - 0 KW - Cytochrome c Group KW - DNA-Binding Proteins KW - Hormones KW - Nuclear Proteins KW - Receptors, Retinoic Acid KW - retinoic acid receptor beta KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - Poly Adenosine Diphosphate Ribose KW - 26656-46-2 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Tretinoin KW - 5688UTC01R KW - DNA-Activated Protein Kinase KW - EC 2.7.11.1 KW - PRKDC protein, human KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Protein-Serine-Threonine Kinases -- metabolism KW - Humans KW - Breast Neoplasms -- metabolism KW - Hormones -- metabolism KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Tumor Cells, Cultured KW - Breast Neoplasms -- pathology KW - Cell Survival -- drug effects KW - Cytochrome c Group -- metabolism KW - Drug Synergism KW - Poly Adenosine Diphosphate Ribose -- metabolism KW - Receptors, Retinoic Acid -- metabolism KW - Tretinoin -- pharmacology KW - Receptors, Retinoic Acid -- biosynthesis KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Apoptosis KW - Mitochondria -- drug effects KW - Antineoplastic Agents -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Receptors, Retinoic Acid -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69928398?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Synergistic+effects+of+retinoic+acid+and+8-chloro-adenosine+3%27%2C5%27-cyclic+monophosphate+on+the+regulation+of+retinoic+acid+receptor+beta+and+apoptosis%3A+involvement+of+mitochondria.&rft.au=Srivastava%2C+R+K%3BSrivastava%2C+A+R%3BCho-Chung%2C+Y+S%3BLongo%2C+D+L&rft.aulast=Srivastava&rft.aufirst=R&rft.date=1999-07-01&rft.volume=5&rft.issue=7&rft.spage=1892&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients. AN - 69927112; 10430060 AB - The MDR1 multidrug resistance gene confers resistance to natural-product anticancer drugs including paclitaxel. We conducted a clinical gene therapy study to determine whether retroviral-mediated transfer of MDR1 in human hematopoietic cells would result in stable engraftment, and possibly expansion, of cells containing this gene after treatment with myelosuppressive doses of paclitaxel. Patients with metastatic breast cancer who achieved a complete or partial remission after standard chemotherapy were eligible for the study. Hematopoietic stem cells (HSCs) were collected by both peripheral blood apheresis and bone marrow harvest after mobilization with a single dose of cyclophosphamide (4 g/m2) and daily filgrastim therapy (10 microg/kg/day). After enrichment for CD34+ cells, one-third of each collection was incubated ex vivo for 72 h with a replication-incompetent retrovirus containing the MDR1 gene (G1MD) in the presence of stem-cell factor, interleukin 3, and interleukin 6. The remaining CD34+ cells were stored without further manipulation. All of the CD34+ cells were reinfused for hematopoietic rescue after conditioning chemotherapy with ifosfamide, carboplatin, and etoposide regimen. After hematopoietic recovery, patients received six cycles of paclitaxel (175 mg/m2 every 3 weeks). Bone marrow and serial peripheral blood samples were obtained and tested for the presence of the MDR1 transgene using a PCR assay. Six patients were enrolled in the study and four patients received infusion of genetically altered cells. The ex vivo transduction efficiency, estimated by the PCR assay, ranged from 0.1 to 0.5%. Three of the four patients demonstrated engraftment of cells containing the MDR1 transgene. The estimated percentage of granulocytes containing the MDR1 transgene ranged from a maximum of 9% of circulating nucleated cells down to the limit of detection of 0.01%. One patient remained positive for the MDR1 transgene throughout all six cycles of paclitaxel therapy, whereas the other 2 patients showed a decrease in the number of cells containing the transgene to undetectable levels. Despite the low level of engraftment of MDR1-marked cells, a correlation was observed between the relative number of granulocytes containing the MDR1 transgene and the granulocyte nadir after paclitaxel therapy. No adverse reactions to the genetic manipulation procedures were detected. Therefore, engraftment of human HSCs transduced with the MDR1 gene can be achieved. However, the overall transduction efficiency and stable engraftment of gene-modified HSCs must be improved before MDR1 gene therapy and in vivo selection with anticancer drugs can be reliably used to protect cancer patients from drug-related myelosuppression. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Cowan, K H AU - Moscow, J A AU - Huang, H AU - Zujewski, J A AU - O'Shaughnessy, J AU - Sorrentino, B AU - Hines, K AU - Carter, C AU - Schneider, E AU - Cusack, G AU - Noone, M AU - Dunbar, C AU - Steinberg, S AU - Wilson, W AU - Goldspiel, B AU - Read, E J AU - Leitman, S F AU - McDonagh, K AU - Chow, C AU - Abati, A AU - Chiang, Y AU - Chang, Y N AU - Gottesman, M M AU - Pastan, I AU - Nienhuis, A AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. kcowan@unmc.edu Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1619 EP - 1628 VL - 5 IS - 7 SN - 1078-0432, 1078-0432 KW - Antigens, CD34 KW - 0 KW - Antineoplastic Agents, Phytogenic KW - DNA, Complementary KW - P-Glycoprotein KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - DNA, Complementary -- genetics KW - Combined Modality Therapy KW - Humans KW - Transduction, Genetic KW - Pilot Projects KW - Transplantation, Autologous KW - Polymerase Chain Reaction KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Genetic Vectors KW - Adult KW - Drug-Related Side Effects and Adverse Reactions -- prevention & control KW - Middle Aged KW - Antigens, CD34 -- analysis KW - Retroviridae -- genetics KW - Female KW - T-Lymphocyte Subsets KW - Breast Neoplasms -- drug therapy KW - Paclitaxel -- adverse effects KW - P-Glycoprotein -- genetics KW - Hematopoietic Stem Cell Transplantation KW - Breast Neoplasms -- therapy KW - Paclitaxel -- therapeutic use KW - Genetic Therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69927112?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Paclitaxel+chemotherapy+after+autologous+stem-cell+transplantation+and+engraftment+of+hematopoietic+cells+transduced+with+a+retrovirus+containing+the+multidrug+resistance+complementary+DNA+%28MDR1%29+in+metastatic+breast+cancer+patients.&rft.au=Cowan%2C+K+H%3BMoscow%2C+J+A%3BHuang%2C+H%3BZujewski%2C+J+A%3BO%27Shaughnessy%2C+J%3BSorrentino%2C+B%3BHines%2C+K%3BCarter%2C+C%3BSchneider%2C+E%3BCusack%2C+G%3BNoone%2C+M%3BDunbar%2C+C%3BSteinberg%2C+S%3BWilson%2C+W%3BGoldspiel%2C+B%3BRead%2C+E+J%3BLeitman%2C+S+F%3BMcDonagh%2C+K%3BChow%2C+C%3BAbati%2C+A%3BChiang%2C+Y%3BChang%2C+Y+N%3BGottesman%2C+M+M%3BPastan%2C+I%3BNienhuis%2C+A&rft.aulast=Cowan&rft.aufirst=K&rft.date=1999-07-01&rft.volume=5&rft.issue=7&rft.spage=1619&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Clin Cancer Res. 1999 Jul;5(7):1607-9 [10430058] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - CD27 signals through PKC in human B cell lymphomas. AN - 69915759; 10419648 AB - Tumour necrosis factor receptor (TNFR) superfamily members play critical roles in the regulation of cell proliferation and death. One member of the TNFR superfamily, CD27, is unique because it is the only covalently linked homodimer in the family. CD27 and its cellular ligand, CD70, have been implicated in the regulation of T cell and B cell interactions that lead to cellular activation and regulation of immunoglobulin expression. Due to the unique nature of CD27, we chose to screen a number of B cell lymphoma cell lines for CD27 and CD70 expression and evaluate CD27 activation by antibody cross-linking. Two cell lines, HT and SU-4, showed greater cellular proliferation when CD27 was cross-lined and this correlated with increased PKC activation. Additionally, in the HT cell line cell surface expression of IgG was increased by CD27 cross-linking. Thus we have identified cellular systems for the study of CD27 signal transduction that will allow definition of the CD27 signal cascade of some B cell lymphomas. Copyright 1999 Academic Press. JF - Cytokine AU - Erlichman, B AU - Howard, O M AD - Laboratory of Molecular Immunoregulation, Division of Basic Science, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 476 EP - 484 VL - 11 IS - 7 SN - 1043-4666, 1043-4666 KW - Antigens, CD27 KW - 0 KW - Phorbol Esters KW - Protein Kinases KW - EC 2.7.- KW - Index Medicus KW - Phorbol Esters -- pharmacology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Lymphoma, Non-Hodgkin KW - Signal Transduction KW - Protein Kinases -- physiology KW - Lymphoma, B-Cell -- immunology KW - Antigens, CD27 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69915759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cytokine&rft.atitle=CD27+signals+through+PKC+in+human+B+cell+lymphomas.&rft.au=Erlichman%2C+B%3BHoward%2C+O+M&rft.aulast=Erlichman&rft.aufirst=B&rft.date=1999-07-01&rft.volume=11&rft.issue=7&rft.spage=476&rft.isbn=&rft.btitle=&rft.title=Cytokine&rft.issn=10434666&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-12 N1 - Date created - 1999-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of reducing sodium and increasing potassium intake for control of hypertension and improving health. AN - 69912007; 10423100 AB - From a world-wide, population perspective, the problem of excessive blood pressure levels for optimal cardiovascular health is immense and growing. Evidence from animal experimentation, observational epidemiology, and randomized clinical trials strongly supports efforts to change nutritional factors in desirable directions, especially to lower dietary salt and increase potassium intake. JF - Clinical and experimental hypertension (New York, N.Y. : 1993) AU - Cutler, J A AD - Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. PY - 1999 SP - 769 EP - 783 VL - 21 IS - 5-6 SN - 1064-1963, 1064-1963 KW - Potassium, Dietary KW - 0 KW - Sodium Chloride, Dietary KW - Index Medicus KW - Body Weight KW - Diet, Sodium-Restricted KW - Age Factors KW - Blood Pressure KW - Humans KW - Adult KW - Clinical Trials as Topic KW - Hypertension -- etiology KW - Middle Aged KW - Male KW - Hypertension -- therapy KW - Female KW - Sodium Chloride, Dietary -- adverse effects KW - Potassium, Dietary -- metabolism KW - Sodium Chloride, Dietary -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69912007?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+and+experimental+hypertension+%28New+York%2C+N.Y.+%3A+1993%29&rft.atitle=The+effects+of+reducing+sodium+and+increasing+potassium+intake+for+control+of+hypertension+and+improving+health.&rft.au=Cutler%2C+J+A&rft.aulast=Cutler&rft.aufirst=J&rft.date=1999-07-01&rft.volume=21&rft.issue=5-6&rft.spage=769&rft.isbn=&rft.btitle=&rft.title=Clinical+and+experimental+hypertension+%28New+York%2C+N.Y.+%3A+1993%29&rft.issn=10641963&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-01 N1 - Date created - 1999-12-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Humanity and radiation: the good, the bad, and the unusual. AN - 69903589; 10414069 AB - Radiation has permeated the universe since time began. People disagree widely about the merits and dangers of nuclear technology. Radiation is often associated in the minds of people with bombs, fallout, destruction, and death rather than with the many benefits of nuclear technology that are present in our daily lives. Rarely do individuals focus on the medical applications of radiation and the fact that nuclear technology saves lives. Over the years, accidents have happened in the nuclear industry; some have produced fatalities, but most proved to be a major source of concern only to the local populace. Since the discovery of naturally occurring radium and uranium and the advent of synthetic radionuclides, a number of consumer products have used radiation, some of which were beneficial and some which were of no benefit at all. JF - Military medicine AU - Holcomb, W F AD - National Institutes of Health, Radiation Safety Branch/Radiation Safety Training Unit, Bethesda, MD 20892-6780, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 520 EP - 525 VL - 164 IS - 7 SN - 0026-4075, 0026-4075 KW - Index Medicus KW - Radioactive Hazard Release -- statistics & numerical data KW - Humans KW - Radioactive Hazard Release -- trends KW - Radiography -- methods KW - Nuclear Medicine -- trends KW - Radiologic Health -- trends KW - Nuclear Medicine -- methods KW - Radiography -- adverse effects KW - Radiography -- trends KW - Radiologic Health -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69903589?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Military+medicine&rft.atitle=Humanity+and+radiation%3A+the+good%2C+the+bad%2C+and+the+unusual.&rft.au=Holcomb%2C+W+F&rft.aulast=Holcomb&rft.aufirst=W&rft.date=1999-07-01&rft.volume=164&rft.issue=7&rft.spage=520&rft.isbn=&rft.btitle=&rft.title=Military+medicine&rft.issn=00264075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-05 N1 - Date created - 1999-08-05 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - NMSP binding to dopamine and serotonin receptors in MPTP-induced parkinsonism: relation to dopa therapy. AN - 69900873; 10416511 AB - We tested the hypothesis that N-methylspiperone binding to dopamine D2 receptors must be reduced when L-dopa therapy of parkinsonism augments the binding of dopamine to the receptors and improves the clinical state expressed by the Hoehn & Yahr stage. A patient with MPTP-induced parkinsonism underwent two positron emission tomographic studies of the D2-like dopamine receptors with N-[11C]methylspiperone (NMSP). The first study took place 3 days after cessation of the L-dopa medication, the second 5 days after its resumption. Noticeable clinical deterioration occurred during both studies, consistent with significant dopamine receptor blockade by NMSP and elevated NMSP binding in both scans. The dopa treatment did not reduce the NMSP binding. On the contrary, the rate of binding of NMSP (k3) was increased on-dopa, compared to off-dopa. The increase was consistent with the slightly greater dopamine receptor density estimated after resumption of the dopa therapy. The NMSP binding to serotonin receptors suggested lower synaptic serotonin on-dopa than off-dopa. The results are consistent with negative correlation between the Hoehn & Yahr stage and the amount of dopamine bound to dopamine D2 receptors. Low synaptic serotonin may explain the depression seen in some patients on dopa for Parkinson's disease. JF - Acta neurologica Scandinavica AU - Borbely, K AU - Brooks, R A AU - Wong, D F AU - Burns, R S AU - Cumming, P AU - Gjedde, A AU - Di Chiro, G AD - Neuroimaging Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 42 EP - 52 VL - 100 IS - 1 SN - 0001-6314, 0001-6314 KW - Antiparkinson Agents KW - 0 KW - Dopamine Antagonists KW - Receptors, Dopamine KW - Receptors, Serotonin KW - Levodopa KW - 46627O600J KW - Spiperone KW - 4X6E73CJ0Q KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine KW - 9P21XSP91P KW - Index Medicus KW - Severity of Illness Index KW - Cerebellum -- diagnostic imaging KW - Humans KW - Adult KW - Putamen -- metabolism KW - Tomography, Emission-Computed KW - Models, Chemical KW - Putamen -- diagnostic imaging KW - Male KW - Cerebellum -- metabolism KW - Receptors, Serotonin -- drug effects KW - Receptors, Dopamine -- drug effects KW - Spiperone -- pharmacokinetics KW - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine -- adverse effects KW - Spiperone -- metabolism KW - Antiparkinson Agents -- therapeutic use KW - Occupational Diseases -- chemically induced KW - Spiperone -- adverse effects KW - Parkinson Disease, Secondary -- diagnosis KW - Parkinson Disease, Secondary -- drug therapy KW - Levodopa -- pharmacology KW - Dopamine Antagonists -- metabolism KW - Binding Sites -- drug effects KW - Dopamine Antagonists -- adverse effects KW - Levodopa -- therapeutic use KW - Dopamine Antagonists -- pharmacokinetics KW - Antiparkinson Agents -- pharmacology KW - Parkinson Disease, Secondary -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69900873?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Acta+neurologica+Scandinavica&rft.atitle=NMSP+binding+to+dopamine+and+serotonin+receptors+in+MPTP-induced+parkinsonism%3A+relation+to+dopa+therapy.&rft.au=Borbely%2C+K%3BBrooks%2C+R+A%3BWong%2C+D+F%3BBurns%2C+R+S%3BCumming%2C+P%3BGjedde%2C+A%3BDi+Chiro%2C+G&rft.aulast=Borbely&rft.aufirst=K&rft.date=1999-07-01&rft.volume=100&rft.issue=1&rft.spage=42&rft.isbn=&rft.btitle=&rft.title=Acta+neurologica+Scandinavica&rft.issn=00016314&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis. AN - 69900405; 10409605 AB - Cystic fibrosis (CF) is characterized by accumulation of activated neutrophils and macrophages on the respiratory epithelial surface (RES); these cells release toxic oxidants, which contribute to the marked epithelial derangements seen in CF. These deleterious consequences are magnified, since reduced glutathione (GSH), an antioxidant present in high concentrations in normal respiratory epithelial lining fluid (ELF), is deficient in CF ELF. To evaluate the feasibility of increasing ELF GSH levels and enhancing RES antioxidant protection, GSH aerosol was delivered (600 mg twice daily for 3 days) to seven patients with CF. ELF total, reduced, and oxidized GSH increased (P < 0.05, all compared with before GSH therapy), suggesting adequate RES delivery and utilization of GSH. Phorbol 12-myristate 13-acetate-stimulated superoxide anion (O2-.) release by ELF inflammatory cells decreased after GSH therapy (P < 0.002). This paralleled observations that GSH added in vitro to CF ELF inflammatory cells suppressed O2-. release (P < 0.001). No adverse effects were noted during treatment. Together, these observations demonstrate the feasibility of using GSH aerosol to restore RES oxidant-antioxidant balance in CF and support the rationale for further clinical evaluation. JF - Journal of applied physiology (Bethesda, Md. : 1985) AU - Roum, J H AU - Borok, Z AU - McElvaney, N G AU - Grimes, G J AU - Bokser, A D AU - Buhl, R AU - Crystal, R G AD - Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA. jhroum@uci.edu Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 438 EP - 443 VL - 87 IS - 1 SN - 8750-7587, 8750-7587 KW - Aerosols KW - 0 KW - Antioxidants KW - Oxidants KW - Superoxides KW - 11062-77-4 KW - Glutathione KW - GAN16C9B8O KW - Glutathione Disulfide KW - ULW86O013H KW - Index Medicus KW - Glutathione Disulfide -- metabolism KW - Humans KW - Inflammation -- drug therapy KW - Epithelial Cells -- metabolism KW - Mononuclear Phagocyte System -- drug effects KW - Superoxides -- metabolism KW - Epithelial Cells -- drug effects KW - Adult KW - Inflammation -- metabolism KW - Female KW - Male KW - Mononuclear Phagocyte System -- metabolism KW - Cystic Fibrosis -- metabolism KW - Cystic Fibrosis -- blood KW - Antioxidants -- metabolism KW - Glutathione -- metabolism KW - Cystic Fibrosis -- drug therapy KW - Lung -- drug effects KW - Oxidants -- metabolism KW - Glutathione -- blood KW - Lung -- metabolism KW - Glutathione -- administration & dosage KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69900405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.atitle=Glutathione+aerosol+suppresses+lung+epithelial+surface+inflammatory+cell-derived+oxidants+in+cystic+fibrosis.&rft.au=Roum%2C+J+H%3BBorok%2C+Z%3BMcElvaney%2C+N+G%3BGrimes%2C+G+J%3BBokser%2C+A+D%3BBuhl%2C+R%3BCrystal%2C+R+G&rft.aulast=Roum&rft.aufirst=J&rft.date=1999-07-01&rft.volume=87&rft.issue=1&rft.spage=438&rft.isbn=&rft.btitle=&rft.title=Journal+of+applied+physiology+%28Bethesda%2C+Md.+%3A+1985%29&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-27 N1 - Date created - 1999-08-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies in transgenic mice indicate a loss of connexin32 function in X-linked Charcot-Marie-Tooth disease. AN - 69892834; 10411340 AB - X-linked Charcot-Marie-Tooth disease (CMTX) is an inherited demyelinating neuropathy caused by mutations in the gene encoding the gap junction protein connexin32 (Cx32). Despite the identification of over 160 different mutations in the Cx32 coding sequence, it is not known whether the mutations cause the disease manifestations through a loss of Cx32 function or through toxic effects on peripheral nerve. We created transgenic mice with a frameshift mutation at codon 175 (175fs), identified in a large CMTX pedigree. Light microscopic examination of the peripheral nerves from adult transgenic animals showed no pathological features. Western blotting did not show transgenic Cx32 protein in any of the 26 lines, although expression of transgenic messenger RNA was detected by reverse-transcriptase polymerase chain reaction and by ribonuclease protection assay. Our findings indicate that the 175fs mutation results in a loss of Cx32 function, without additional toxic effects. JF - Journal of neuropathology and experimental neurology AU - Abel, A AU - Bone, L J AU - Messing, A AU - Scherer, S S AU - Fischbeck, K H AD - Neurogenetics Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1250, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 702 EP - 710 VL - 58 IS - 7 SN - 0022-3069, 0022-3069 KW - Connexins KW - 0 KW - RNA, Messenger KW - connexin 32 KW - Index Medicus KW - Rats KW - Animals KW - RNA, Messenger -- metabolism KW - Frameshift Mutation -- physiology KW - Mice KW - Femoral Nerve -- pathology KW - Mice, Transgenic -- genetics KW - Charcot-Marie-Tooth Disease -- physiopathology KW - Charcot-Marie-Tooth Disease -- pathology KW - Genetic Linkage -- genetics KW - Connexins -- physiology KW - X Chromosome -- genetics KW - Connexins -- metabolism KW - Charcot-Marie-Tooth Disease -- metabolism KW - Charcot-Marie-Tooth Disease -- genetics KW - Connexins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69892834?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuropathology+and+experimental+neurology&rft.atitle=Studies+in+transgenic+mice+indicate+a+loss+of+connexin32+function+in+X-linked+Charcot-Marie-Tooth+disease.&rft.au=Abel%2C+A%3BBone%2C+L+J%3BMessing%2C+A%3BScherer%2C+S+S%3BFischbeck%2C+K+H&rft.aulast=Abel&rft.aufirst=A&rft.date=1999-07-01&rft.volume=58&rft.issue=7&rft.spage=702&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuropathology+and+experimental+neurology&rft.issn=00223069&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Including children and adolescents with schizophrenia in medication-free research. AN - 69889727; 10401453 AB - There has been an increasing focus on the ethical issues raised by studies requiring the withdrawal of effective medication in schizophrenic adults. This article examines the risks and benefits of a medication-free period for pediatric patients with treatment-refractory schizophrenia who are participating in an ongoing study. Between April 1993 and March 1998, 31 children and adolescents were admitted with a diagnosis of treatment-resistant, childhood-onset schizophrenia. Parental consent was obtained so that patients could participate in a medication-free research period. Patients were evaluated at screening, at the end of a 4-week washout, at the completion of a 6- to 8-week atypical neuroleptic trial, and at a 2- to 4-year follow-up. At the completion of a 4-week drug-free period, seven patients (23%) were diagnosed with another disorder on the basis of data gained from the drug-free period and their lack of schizophrenic symptoms. Their revised diagnoses were posttraumatic stress disorder (N = 1), an atypical psychosis labeled "multidimensionally impaired" (N = 4), and personality disorder (N = 2). At follow-up, three of these patients remained free of neuroleptic therapy. For eight patients (26%), the washout was curtailed because of rapid and severe deterioration of their schizophrenic symptoms. For children and adolescents with treatment-refractory schizophrenia, a medication-free period can be conducted safely for at least 4 weeks for inpatients. Such trials are useful on clinical grounds and for providing homogeneous patient groups for research. This study also highlights the necessity of having access to hospitalization to observe children and adolescents with psychotic symptoms while medication free. JF - The American journal of psychiatry AU - Kumra, S AU - Briguglio, C AU - Lenane, M AU - Goldhar, L AU - Bedwell, J AU - Venuchekov, J AU - Jacobsen, L K AU - Rapoport, J L AD - Child Psychiatry Branch, NIMH, Bethesda, MD 20892-1600, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1065 EP - 1068 VL - 156 IS - 7 SN - 0002-953X, 0002-953X KW - Antipsychotic Agents KW - 0 KW - Abridged Index Medicus KW - Bioethics KW - Index Medicus KW - National Institute of Mental Health KW - Biomedical and Behavioral Research KW - Mental Health Therapies KW - Empirical Approach KW - Age Factors KW - Substance Withdrawal Syndrome KW - Humans KW - Child KW - Diagnostic Errors KW - Personality Disorders -- diagnosis KW - Hospitalization KW - Adult KW - Treatment Outcome KW - Follow-Up Studies KW - Psychotic Disorders -- diagnosis KW - Adolescent KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Female KW - Male KW - Schizophrenia, Childhood -- diagnosis KW - Antipsychotic Agents -- administration & dosage KW - Clinical Protocols -- standards KW - Schizophrenia, Childhood -- psychology KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia, Childhood -- drug therapy KW - Ethics, Medical KW - Research Design -- standards KW - Withholding Treatment KW - Risk Assessment KW - Mentally Ill Persons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69889727?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Including+children+and+adolescents+with+schizophrenia+in+medication-free+research.&rft.au=Kumra%2C+S%3BBriguglio%2C+C%3BLenane%2C+M%3BGoldhar%2C+L%3BBedwell%2C+J%3BVenuchekov%2C+J%3BJacobsen%2C+L+K%3BRapoport%2C+J+L&rft.aulast=Kumra&rft.aufirst=S&rft.date=1999-07-01&rft.volume=156&rft.issue=7&rft.spage=1065&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-30 N1 - Date created - 1999-07-30 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 2001 Feb;158(2):324 [11156827] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Arsenic: health effects, mechanisms of actions, and research issues. AN - 69888890; 10379007 AB - A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens. JF - Environmental health perspectives AU - Abernathy, C O AU - Liu, Y P AU - Longfellow, D AU - Aposhian, H V AU - Beck, B AU - Fowler, B AU - Goyer, R AU - Menzer, R AU - Rossman, T AU - Thompson, C AU - Waalkes, M AD - Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA. abernathy.charles@epa.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 593 EP - 597 VL - 107 IS - 7 SN - 0091-6765, 0091-6765 KW - DNA KW - 9007-49-2 KW - Arsenic KW - N712M78A8G KW - Index Medicus KW - Dose-Response Relationship, Drug KW - DNA Damage KW - Humans KW - Neoplasms -- chemically induced KW - DNA -- drug effects KW - Arsenic -- toxicity KW - Arsenic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69888890?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Arsenic%3A+health+effects%2C+mechanisms+of+actions%2C+and+research+issues.&rft.au=Abernathy%2C+C+O%3BLiu%2C+Y+P%3BLongfellow%2C+D%3BAposhian%2C+H+V%3BBeck%2C+B%3BFowler%2C+B%3BGoyer%2C+R%3BMenzer%2C+R%3BRossman%2C+T%3BThompson%2C+C%3BWaalkes%2C+M&rft.aulast=Abernathy&rft.aufirst=C&rft.date=1999-07-01&rft.volume=107&rft.issue=7&rft.spage=593&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-29 N1 - Date created - 1999-07-29 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Natl Cancer Inst. 1968 Mar;40(3):453-63 [5644201] Environ Health Perspect. 1999 May;107(5):359-65 [10210691] Toxicol Appl Pharmacol. 1990 Dec;106(3):462-8 [2260094] Chem Biol Interact. 1993 Sep;88(2-3):89-14 [8403081] Biochem Biophys Res Commun. 1995 Feb 6;207(1):244-9 [7857272] Eur J Pharmacol. 1995 Dec 7;293(4):455-62 [8748699] Toxicol Appl Pharmacol. 1996 Oct;140(2):471-86 [8887465] Annu Rev Pharmacol Toxicol. 1997;37:397-419 [9131259] Mutat Res. 1997 Jun;386(3):263-77 [9219564] J Pharmacol Exp Ther. 1997 Jul;282(1):192-200 [9223554] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10907-12 [9380733] Toxicol Appl Pharmacol. 1998 Jan;148(1):65-70 [9465265] Cad Saude Publica. 1998;14 Suppl 3:193-8 [9819479] Int J Epidemiol. 1998 Oct;27(5):871-7 [9839746] Atherosclerosis. 1998 Dec;141(2):249-57 [9862173] Proc Natl Acad Sci U S A. 1989 Jan;86(1):99-103 [2911585] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of autoimmune premature ovarian failure. AN - 69885353; 10402388 AB - There is no known immunosuppressive therapy for autoimmune premature ovarian failure that has been proven safe and effective by prospective randomized placebo-controlled study. Nevertheless, immunosuppression using corticosteroids has been used on an empirical basis for this condition. Here we present two cases of young women with premature ovarian failure who were treated with glucocorticoids in the hopes of restoring fertility. The first case illustrates the potential benefit of such therapy, and the second case illustrates a potential risk. The first patient with histologically proven autoimmune oophoritis was treated with alternate day glucocorticoid treatment. She had return of menstrual bleeding six times and ovulatory progesterone concentrations four times over a 16 week period. The second patient with presumed but unconfirmed autoimmune ovarian failure was referred to us after having been treated with a 9 month course of corticosteroids. During that treatment her menses did not resume. The corticosteroid treatment was complicated by iatrogenic Cushing syndrome and osteonecrosis of the knee. Identifying patients with autoimmune premature ovarian failure presents the opportunity to restore ovarian function by treating these patients with the proper immune modulation therapy. On the other hand, potent immune modulation therapy can have major complications. Corticosteroid therapy for autoimmune premature ovarian failure should be limited to use in placebo-controlled trials designed to evaluate the safety and efficacy of such treatment. JF - Human reproduction (Oxford, England) AU - Kalantaridou, S N AU - Braddock, D T AU - Patronas, N J AU - Nelson, L M AD - Section on Women's Health Research, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1777 EP - 1782 VL - 14 IS - 7 SN - 0268-1161, 0268-1161 KW - Glucocorticoids KW - 0 KW - Immunosuppressive Agents KW - Dexamethasone KW - 7S5I7G3JQL KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Dexamethasone -- therapeutic use KW - Cushing Syndrome -- chemically induced KW - Iatrogenic Disease KW - Oophoritis -- physiopathology KW - Prednisone -- therapeutic use KW - Humans KW - Knee KW - Osteonecrosis -- pathology KW - Oophoritis -- drug therapy KW - Osteonecrosis -- chemically induced KW - Dexamethasone -- adverse effects KW - Oophoritis -- pathology KW - Adult KW - Female KW - Primary Ovarian Insufficiency -- pathology KW - Primary Ovarian Insufficiency -- physiopathology KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- drug therapy KW - Primary Ovarian Insufficiency -- drug therapy KW - Glucocorticoids -- adverse effects KW - Glucocorticoids -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69885353?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+reproduction+%28Oxford%2C+England%29&rft.atitle=Treatment+of+autoimmune+premature+ovarian+failure.&rft.au=Kalantaridou%2C+S+N%3BBraddock%2C+D+T%3BPatronas%2C+N+J%3BNelson%2C+L+M&rft.aulast=Kalantaridou&rft.aufirst=S&rft.date=1999-07-01&rft.volume=14&rft.issue=7&rft.spage=1777&rft.isbn=&rft.btitle=&rft.title=Human+reproduction+%28Oxford%2C+England%29&rft.issn=02681161&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-13 N1 - Date created - 1999-09-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mitogen-activated protein kinase pathway is dispensable for microtubule-active drug-induced Raf-1/Bcl-2 phosphorylation and apoptosis in leukemia cells. AN - 69883887; 10400418 AB - Raf-1 activation and Bcl-2 hyperphosphorylation following treatment with paclitaxel (Taxol) or other microtubule-active drugs is associated with mitotic arrest. Here we show that microtubule-active drugs do not activate the mitogen-activated protein kinase (MAPK) pathway in leukemia cells. PD98059, a MEK inhibitor, and SB202190, a p38 MAP kinase inhibitor, do not abrogate Bcl-2 phosphorylation nor apoptosis. Simultaneously with PARP cleavage, paclitaxel induces cleavage of Bcl-2 protein yielding a potentially pro-apoptotic 22 kDa product. In comparison, the stimulation of Raf-1 by phorbol ester (TPA) activates the MAPK pathway, causes MAPK-dependent p21WAF1/CIP1 induction, Rb dephosphorylation and growth arrest without Bcl-2 phosphorylation or apoptosis. Like TPA, cAMP induces p21WAF1/CIP1 but does not cause Bcl-2 phosphorylation. MEKK1 and Ras, upstream activators of JNK and ERK MAPK, also fail to induce Bcl-2 hyperphosphorylation. Although Lck tyrosine kinase has been recently implicated in Raf-1 activation during mitotic arrest, microtubule-active drugs induce Raf-1/Bcl-2 hyperphosphorylation and apoptosis in a Lck-deficient Jurkat cells. Therefore, microtubule-active drugs induce apoptosis which is associated with Raf-1 and Bcl-2 phosphorylation and Bcl-2 cleavage but is independent of the MAPK pathway. In contrast, TPA-activated MAPK pathway causes p21WAF1/CIP1-dependent growth arrest without apoptosis. JF - Leukemia AU - Blagosklonny, M V AU - Chuman, Y AU - Bergan, R C AU - Fojo, T AD - Medicine Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1028 EP - 1036 VL - 13 IS - 7 SN - 0887-6924, 0887-6924 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Proto-Oncogene Proteins c-bcl-2 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-raf KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - MAP Kinase Kinase Kinase 1 KW - EC 2.7.11.25 KW - MAP3K1 protein, human KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Genes, ras KW - Protein-Serine-Threonine Kinases -- metabolism KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Apoptosis -- drug effects KW - Tetradecanoylphorbol Acetate -- therapeutic use KW - Paclitaxel -- therapeutic use KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Leukemia, Myeloid -- drug therapy KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Leukemia, Myeloid -- metabolism KW - Proto-Oncogene Proteins c-raf -- metabolism KW - Microtubules -- drug effects KW - Leukemia, Myeloid -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69883887?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Mitogen-activated+protein+kinase+pathway+is+dispensable+for+microtubule-active+drug-induced+Raf-1%2FBcl-2+phosphorylation+and+apoptosis+in+leukemia+cells.&rft.au=Blagosklonny%2C+M+V%3BChuman%2C+Y%3BBergan%2C+R+C%3BFojo%2C+T&rft.aulast=Blagosklonny&rft.aufirst=M&rft.date=1999-07-01&rft.volume=13&rft.issue=7&rft.spage=1028&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-26 N1 - Date created - 1999-07-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of mRNA export by nutritional status in fission yeast. AN - 69864377; 10388805 AB - We have isolated a mutation in nup184(nup184-1) that is synthetically lethal with the mRNA export defective rae1-167 mutation in Schizosaccharomyces pombe. The consequence of the synthetic lethality is a defect in mRNA export. The predicted Nup184p is similar to Nup188p of Saccharomyces cerevisiae, and a Nup184p-GFP fusion localizes to the nuclear periphery in a punctate pattern. The Deltanup184 null mutant is viable and also is synthetically lethal with rae1-167. In a rae1(+) background, both the nup184-1 and Deltanup184 mutations confer sensitivity to growth in nutrient-rich medium (YES) that is accompanied by nuclear poly(A)+ RNA accumulation. Removal of the cAMP-dependent protein kinase, Pka1p, relieved the growth and mRNA export defects of nup184 mutants when grown in nutrient-rich medium. The activation of Pka1p is necessary, but not sufficient, to cause the severe poly(A)+ RNA export defects when nup184 mutant cells are incubated in YES, suggesting nutritional status can also regulate poly(A)+ RNA export. Our results suggest that the regulation of poly(A)+ RNA export by Pka1p kinase appears to be indirect, via a translation-dependent step, but post-translationally in response to YES. JF - Genetics AU - Whalen, W A AU - Yoon, J H AU - Shen, R AU - Dhar, R AD - Basic Sciences Laboratory, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 827 EP - 838 VL - 152 IS - 3 SN - 0016-6731, 0016-6731 KW - Culture Media KW - 0 KW - Fungal Proteins KW - RNA, Messenger KW - Cyclic AMP KW - E0399OZS9N KW - Index Medicus KW - Genotype KW - Protein Biosynthesis KW - Fungal Proteins -- metabolism KW - Cell Nucleus -- ultrastructure KW - Cell Nucleus -- metabolism KW - Temperature KW - Cyclic AMP -- metabolism KW - Fungal Proteins -- genetics KW - Models, Biological KW - Genes, Lethal KW - Mutagenesis KW - Schizosaccharomyces -- genetics KW - RNA, Messenger -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69864377?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Regulation+of+mRNA+export+by+nutritional+status+in+fission+yeast.&rft.au=Whalen%2C+W+A%3BYoon%2C+J+H%3BShen%2C+R%3BDhar%2C+R&rft.aulast=Whalen&rft.aufirst=W&rft.date=1999-07-01&rft.volume=152&rft.issue=3&rft.spage=827&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-23 N1 - Date created - 1999-09-23 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF055035; GENBANK N1 - SuppNotes - Cited By: J Bacteriol. 1969 Sep;99(3):807-14 [5370278] J Cell Biol. 1998 Jun 29;141(7):1575-87 [9647650] Plasmid. 1986 Mar;15(2):156-8 [3010354] Methods Enzymol. 1991;194:795-823 [2005825] EMBO J. 1991 Dec;10(12):3759-68 [1657594] Genes Dev. 1992 Jul;6(7):1173-89 [1628825] Genes Dev. 1992 Oct;6(10):1914-26 [1398069] Gene. 1993 Jan 15;123(1):127-30 [8422996] Nucleic Acids Res. 1993 Jun 25;21(12):2955-6 [8332516] J Biol Chem. 1994 Apr 1;269(13):9632-7 [8144551] EMBO J. 1995 Jan 3;14(1):76-87 [7828598] Gene. 1994 Dec 30;151(1-2):215-20 [7828877] J Biol Chem. 1995 Mar 31;270(13):7411-9 [7706287] Cell. 1995 Apr 21;81(2):153-9 [7537634] Nature. 1995 Dec 14;378(6558):739-43 [7501024] EMBO J. 1995 Dec 1;14(23):5939-46 [8846786] Genetics. 1995 Jun;140(2):457-67 [7498728] Science. 1996 Mar 15;271(5255):1513-8 [8599106] J Cell Biol. 1996 Apr;133(1):5-14 [8601613] Genes Dev. 1996 Jul 1;10(13):1608-20 [8682292] J Cell Biol. 1996 Jun;133(6):1141-52 [8682854] J Cell Biol. 1996 Jun;133(6):1153-62 [8682855] J Cell Biol. 1996 Oct;135(2):329-39 [8896592] EMBO J. 1997 Feb 17;16(4):807-16 [9049309] Nature. 1997 Apr 24;386(6627):779-87 [9126736] Curr Opin Cell Biol. 1997 Jun;9(3):412-9 [9159081] Mol Biol Cell. 1997 May;8(5):825-41 [9168469] Yeast. 1997 Sep 30;13(12):1167-79 [9301023] Science. 1997 Oct 3;278(5335):141-4 [9311922] Cell. 1997 Sep 19;90(6):1041-50 [9323132] Genes Dev. 1997 Nov 1;11(21):2845-56 [9353254] Genes Dev. 1997 Nov 1;11(21):2857-68 [9353255] Curr Biol. 1997 Oct 1;7(10):767-75 [9368759] Mol Cell Biol. 1997 Dec;17(12):7047-60 [9372936] Nature. 1997 Nov 20;390(6657):308-11 [9384386] Mol Biol Cell. 1998 Feb;9(2):355-73 [9450961] EMBO J. 1998 Feb 16;17(4):1107-19 [9463388] Cell. 1998 Feb 6;92(3):327-36 [9476893] Genes Dev. 1998 May 15;12(10):1453-63 [9585505] Trends Biochem Sci. 1998 May;23(5):185-9 [9612083] RNA. 1998 Apr;4(4):351-64 [9630243] Proc Natl Acad Sci U S A. 1974 Jul;71(7):2658-62 [4605329] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Residential radon exposure and risk of lung cancer in Missouri. AN - 69862975; 10394313 AB - This study investigated residential radon exposure and lung cancer risk, using both standard radon dosimetry and a new radon monitoring technology that, evidence suggests, is a better measure of cumulative radon exposure. Missouri women (aged 30 to 84 years) newly diagnosed with primary lung cancer during the period January 1, 1993, to January 31, 1994, were invited to participate in this population-based case-control study. Both indoor air radon detectors and CR-39 alpha-particle detectors (surface monitors) were used. When surface monitors were used, a significant trend in lung cancer odds ratios was observed for 20-year time-weighted-average radon concentrations. When surface monitors were used, but not when standard radon dosimetry was used, a significant lung cancer risk was found for radon concentrations at and above the action level for mitigation of houses currently used in the United States (148 Bqm-3). The risk was below the action level used in Canada (750 Bqm-3) and many European countries (200-400 Bqm-3). JF - American journal of public health AU - Alavanja, M C AU - Lubin, J H AU - Mahaffey, J A AU - Brownson, R C AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md. 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1042 EP - 1048 VL - 89 IS - 7 SN - 0090-0036, 0090-0036 KW - Air Pollutants, Radioactive KW - 0 KW - Radon KW - Q74S4N8N1G KW - Abridged Index Medicus KW - Index Medicus KW - Missouri -- epidemiology KW - Housing KW - Humans KW - Aged KW - Likelihood Functions KW - Smoking -- epidemiology KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Surveys and Questionnaires KW - Case-Control Studies KW - Epidemiological Monitoring KW - Middle Aged KW - Environmental Monitoring -- methods KW - Female KW - Lung Neoplasms -- epidemiology KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- epidemiology KW - Air Pollutants, Radioactive -- adverse effects KW - Lung Neoplasms -- chemically induced KW - Radon -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69862975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+public+health&rft.atitle=Residential+radon+exposure+and+risk+of+lung+cancer+in+Missouri.&rft.au=Alavanja%2C+M+C%3BLubin%2C+J+H%3BMahaffey%2C+J+A%3BBrownson%2C+R+C&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1999-07-01&rft.volume=89&rft.issue=7&rft.spage=1042&rft.isbn=&rft.btitle=&rft.title=American+journal+of+public+health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-22 N1 - Date created - 1999-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1988 Jul 28;334(6180):338-40 [3393224] Cancer Causes Control. 1997 Nov;8(6):883-93 [9427431] Biometrics. 1990 Dec;46(4):963-75 [2085641] Am J Epidemiol. 1991 Aug 15;134(4):421-32 [1877602] Science. 1991 Nov 8;254(5033):777 [1948055] Health Phys. 1992 Apr;62(4):351-5 [1597387] Health Phys. 1993 May;64(5):485-90 [8491599] J Natl Cancer Inst. 1993 Dec 1;85(23):1906-16 [8230280] J Natl Cancer Inst. 1994 Dec 21;86(24):1829-37 [7990157] Radiat Res. 1995 Dec;144(3):329-41 [7494877] Environ Health Perspect. 1995 Nov;103(11):1042-6 [8605854] Epidemiology. 1996 Sep;7(5):490-7 [8862979] BMJ. 1996 Nov 16;313(7067):1233-5 [8939111] Health Phys. 1997 Jan;72(1):114-9 [8972836] J Natl Cancer Inst. 1997 Jan 1;89(1):49-57 [8978406] J Expo Anal Environ Epidemiol. 1996 Oct-Dec;6(4):425-37 [9087863] Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3765-70 [9108052] Health Phys. 1990 Dec;59(6):807-17 [2228608] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sequence-dependent mutations in a shuttle vector plasmid replicated in a mismatch repair deficient human cell line. AN - 69853362; 10383903 AB - We utilized a shuttle vector plasmid (pLSC) to assess the role of DNA sequence and mismatch repair on mutagenesis in human cells. pLSC contains an interrupted 29 bp mononucleotide poly(G) run within a bacterial suppressor tRNA gene, which acts as a highly sensitive mutagenic target for detection of base substitution and frameshift mutations. The frequency of spontaneous mutations in pLSC was found to be similar after replication in either the hMSH6 (GT binding protein) mismatch repair-deficient MT1 line or its parental, mismatch repair-proficient line, TK6. However, the classes of plasmid mutations showed distinct differences in the two cell lines. Single base deletions comprised 48% of the mutations in the 56 independent pLSC plasmids sequenced from MT1 cells while these represented only 18% of the 40 independent pLSC mutants sequenced from the wild-type TK6 cells (P = 0.001). Virtually all the deletions included the mononucleotide run. In contrast, in pSP189, which contains the unmodified supF tRNA without the mononucleotide sequence, no single base deletions were observed for either cell line (P < 0.001). UV treatment of pLSC and pSP189 resulted in a 12-140-fold increase in mutations in TK6 and MT1 cells. These were predominately single base substitution mutations without a large increase in deletion mutations in the mononucleotide run in pLSC. These data indicate that a mononucleotide poly(G) run promotes single base deletion mutations. This effect is enhanced in a hMSH6 mismatch repair-deficient cell line and is independent of UV-induced mutagenesis. JF - Carcinogenesis AU - Tobi, S E AU - Levy, D D AU - Seidman1, M M AU - Kraemer1, K H AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1293 EP - 1301 VL - 20 IS - 7 SN - 0143-3334, 0143-3334 KW - supF tRNA KW - 0 KW - RNA, Transfer KW - 9014-25-9 KW - Index Medicus KW - Mutagenesis -- radiation effects KW - Ultraviolet Rays KW - Base Sequence KW - DNA Replication -- radiation effects KW - RNA, Transfer -- genetics KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Mutagenesis -- genetics KW - Genes, Suppressor KW - Cell Line KW - Sequence Deletion KW - DNA Repair -- genetics KW - Plasmids -- genetics KW - Genetic Vectors -- radiation effects KW - Genetic Vectors -- genetics KW - Base Pair Mismatch -- genetics KW - Plasmids -- radiation effects KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69853362?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Sequence-dependent+mutations+in+a+shuttle+vector+plasmid+replicated+in+a+mismatch+repair+deficient+human+cell+line.&rft.au=Tobi%2C+S+E%3BLevy%2C+D+D%3BSeidman1%2C+M+M%3BKraemer1%2C+K+H&rft.aulast=Tobi&rft.aufirst=S&rft.date=1999-07-01&rft.volume=20&rft.issue=7&rft.spage=1293&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - BALB/c.CBA/N mice carrying the defective Btk(xid) gene are resistant to pristane-induced plasmacytomagenesis. AN - 69853282; 10383938 AB - The X-chromosome from the CBA/N mouse which carries the defective Bruton's tyrosine kinase (Btk) allele (Xxid) has been introgressively backcrossed onto the plasmacytoma (PCT) induction-susceptible BALB/cAN. Inbred BALB/c.CBA/N-xid/xid (C.CBA/N) mice raised and maintained in our conventional colony were given three 0.5 ml injections of pristane and were highly refractory to PCT induction. Only one PCT was found among 59 mice followed for > or =300 days. Twenty mice were examined at day 200 for foci of plasma cells in the oil granuloma. Ten mice had small foci of plasma cells, most of which were plasmacytotic, embedded in the inflammatory oil granuloma. In one there were multiple foci, but most of the mice had only one or two foci. F1 hybrid XxidY males derived from CBA/N females crossed to BALB/cAnPt were also resistant to PCT induction, while heterozygous and homozygous XY males were susceptible. C.CBA/N mice can develop extensive mucosal plasma cells as well as plasma cell accumulations in oil granuloma tissue, but the precursors of these plasma cells do not give rise to PCT in genetically susceptible hosts. The failure of C.CBA/N mice to develop PCT is probably due to the elimination of B cell clones that can be perpetuated by repeated exposure to thymus-independent type 2 antigens. JF - International immunology AU - Potter, M AU - Wax, J S AU - Hansen, C T AU - Kenny, J J AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Building 37, Room 2B04, 37 Convent Drive, MSC4255, Bethesda, MD 20892, USA. Rockville, MD 20850-4390, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1059 EP - 1064 VL - 11 IS - 7 SN - 0953-8178, 0953-8178 KW - Carcinogens KW - 0 KW - Terpenes KW - pristane KW - 26HZV48DT1 KW - Agammaglobulinaemia tyrosine kinase KW - EC 2.7.10.1 KW - Protein-Tyrosine Kinases KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Alleles KW - Crosses, Genetic KW - Mice KW - Mice, Inbred BALB C KW - Male KW - Female KW - Peritoneal Neoplasms -- chemically induced KW - Genetic Predisposition to Disease -- enzymology KW - Plasmacytoma -- chemically induced KW - Plasmacytoma -- pathology KW - Peritoneal Neoplasms -- genetics KW - Peritoneal Neoplasms -- pathology KW - Plasmacytoma -- genetics KW - Protein-Tyrosine Kinases -- genetics KW - Genetic Predisposition to Disease -- immunology KW - Peritoneal Neoplasms -- enzymology KW - Plasmacytoma -- enzymology KW - X Chromosome -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69853282?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunology&rft.atitle=BALB%2Fc.CBA%2FN+mice+carrying+the+defective+Btk%28xid%29+gene+are+resistant+to+pristane-induced+plasmacytomagenesis.&rft.au=Potter%2C+M%3BWax%2C+J+S%3BHansen%2C+C+T%3BKenny%2C+J+J&rft.aulast=Potter&rft.aufirst=M&rft.date=1999-07-01&rft.volume=11&rft.issue=7&rft.spage=1059&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-17 N1 - Date created - 1999-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rare diseases.3: Wegener's granulomatosis. AN - 69846719; 10377211 JF - Thorax AU - Langford, C A AU - Hoffman, G S AD - Immunologic Diseases Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 629 EP - 637 VL - 54 IS - 7 SN - 0040-6376, 0040-6376 KW - Antibodies, Antineutrophil Cytoplasmic KW - 0 KW - Biomarkers KW - Glucocorticoids KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Index Medicus KW - Drug Therapy, Combination KW - Neutrophil Activation KW - Cyclophosphamide -- therapeutic use KW - Disease Susceptibility KW - Humans KW - Adult KW - Antibodies, Antineutrophil Cytoplasmic -- blood KW - Glucocorticoids -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Biomarkers -- blood KW - Male KW - Female KW - Prevalence KW - Granulomatosis with Polyangiitis -- etiology KW - Granulomatosis with Polyangiitis -- diagnosis KW - Granulomatosis with Polyangiitis -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69846719?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Thorax&rft.atitle=Rare+diseases.3%3A+Wegener%27s+granulomatosis.&rft.au=Langford%2C+C+A%3BHoffman%2C+G+S&rft.aulast=Langford&rft.aufirst=C&rft.date=1999-07-01&rft.volume=54&rft.issue=7&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Thorax&rft.issn=00406376&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-02 N1 - Date created - 1999-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Rheum Dis Clin North Am. 1995 Nov;21(4):987-1011 [8592745] Ann Intern Med. 1996 Mar 1;124(5):477-84 [8602705] Clin Exp Immunol. 1996 May;104 Suppl 1:77-82 [8625549] N Engl J Med. 1996 Jul 4;335(1):16-20 [8637536] Am J Surg Pathol. 1991 Apr;15(4):315-33 [2006712] J Leukoc Biol. 1991 Dec;50(6):539-46 [1658170] Pneumologie. 1991 Jul;45(7):570-4 [1946253] Ann Intern Med. 1992 Mar 15;116(6):488-98 [1739240] Ann Intern Med. 1967 Aug;67(2):393-8 [6036397] Am J Pathol. 1973 May;71(2):345-8 [4713944] Am J Med. 1977 Jul;63(1):131-41 [327802] Am J Pathol. 1979 Sep;96(3):673-706 [382868] Ann Intern Med. 1983 Jan;98(1):76-85 [6336643] Br Med J (Clin Res Ed). 1982 Aug 28-Sep 4;285(6342):606 [6297657] Infect Immun. 1983 Sep;41(3):1016-23 [6193063] Mayo Clin Proc. 1985 Jan;60(1):27-32 [3871238] Clin Nephrol. 1992 Mar;37(3):124-30 [1348669] Arthritis Rheum. 1992 Nov;35(11):1322-9 [1445449] J Am Soc Nephrol. 1996 May;7(5):694-701 [8738804] Arthritis Rheum. 1996 Oct;39(10):1754-60 [8843868] Arthritis Rheum. 1996 Dec;39(12):2052-61 [8961911] J Clin Invest. 1997 Sep 15;100(6):1416-24 [9294107] Rheum Dis Clin North Am. 1997 Nov;23(4):841-53 [9361158] Arthritis Rheum. 1997 Nov;40(11):2030-8 [9365093] Nat Med. 1997 Dec;3(12):1346-53 [9396604] Eur J Clin Invest. 1997 Nov;27(11):893-9 [9395784] Arthritis Rheum. 1997 Dec;40(12):2187-98 [9416856] Kidney Int. 1998 Mar;53(3):743-53 [9507222] J Immunol. 1998 Apr 1;160(7):3602-9 [9531324] Cleve Clin J Med. 1998 Mar;65(3):135-40 [9540246] J Exp Med. 1998 Aug 3;188(3):577-88 [9687534] Arthritis Rheum. 1998 Sep;41(9):1521-37 [9751084] Clin Exp Rheumatol. 1998 Sep-Oct;16(5):527-32 [9779298] Br Med J. 1958 Aug 2;2(5091):265-70 [13560836] Lancet. 1985 Feb 23;1(8426):425-9 [2857806] N Engl J Med. 1988 Jun 23;318(25):1651-7 [2453802] Arch Intern Med. 1988 Oct;148(10):2293-5 [3263099] Ann Intern Med. 1989 Jul 1;111(1):28-40 [2660645] Blood. 1989 Nov 1;74(6):1888-93 [2679910] Immunology. 1989 Oct;68(2):196-8 [2478451] Arch Intern Med. 1989 Nov;149(11):2461-5 [2684074] Am J Surg Pathol. 1990 Jun;14(6):555-64 [2337204] Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115-9 [2161532] Clin Exp Immunol. 1990 Aug;81(2):311-4 [1696867] Lancet. 1990 Sep 22;336(8717):709-11 [1975893] Am J Med. 1990 Oct;89(4):403-10 [2220874] Am Rev Respir Dis. 1991 Feb;143(2):275-8 [1990940] Am Rev Respir Dis. 1991 Feb;143(2):401-7 [1990960] Arthritis Rheum. 1993 Mar;36(3):365-71 [8452581] Kidney Int. 1993 Mar;43(3):682-92 [8455368] Ann Neurol. 1993 Jan;33(1):4-9 [8388187] Clin Exp Immunol. 1993 Dec;94(3):440-6 [7504599] Clin Nephrol. 1993 Nov;40(5):256-64 [8281714] Adv Exp Med Biol. 1993;336:245-51 [8296613] Adv Exp Med Biol. 1993;336:473-6 [8296660] Adv Exp Med Biol. 1993;336:487-9 [8296662] Clin Exp Immunol. 1994 Feb;95(2):244-50 [8306499] Arthritis Rheum. 1994 Jun;37(6):919-24 [8003065] Ann Intern Med. 1994 Oct 1;121(7):484-91 [8067646] Exp Nephrol. 1993 May-Jun;1(3):190-5 [7915959] Clin Exp Immunol. 1994 Sep;97(3):458-65 [8082300] Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):522-6 [7842215] Arthritis Rheum. 1995 May;38(5):608-13 [7748215] Arthritis Rheum. 1995 Aug;38(8):1120-7 [7639809] Ren Fail. 1995 Mar;17(2):125-33 [7644763] Clin Exp Immunol. 1995 Oct;102(1):98-105 [7554407] Ann Intern Med. 1995 Dec 15;123(12):925-32 [7486487] Arthritis Rheum. 1996 Jan;39(1):87-92 [8546743] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation. AN - 69842772; 10379865 AB - The transition of normal epithelium to invasive carcinoma occurs sequentially. In colorectal and cervical carcinogenesis, this transition is reflected by histomorphologically defined grades of increasing dysplasia that untreated may progress to invasive disease. In an attempt to understand the role of chromosomal aberrations during tumorigenesis we have applied comparative genomic hybridization using DNA extracted from defined stages of colorectal and cervical tumors, from low- and high-grade astrocytic tumors and from diploid and aneuploid breast carcinomas. Genetic instability, as measured by the number of chromosomal copy alterations per case, increases significantly at the transition from precursor lesions to invasive carcinomas and continues to increase with tumor stage. Aggressive tumors have a higher number of copy alterations per case. High-level copy number changes (amplifications) become more prevalent in advanced-stage disease. Subtractive karyograms of chromosomal gains and losses were used to map tumor stage-specific chromosomal aberrations and clearly showed that nonrandom chromosomal aberrations occur during disease progression. In colorectal and cervical tumors, chromosomal copy number changes were correlated with nuclear DNA content, proliferative activity, expression levels of the tumor suppressor gene TP53, and the cyclin-dependent kinase inhibitor p21/WAF1, as well as the presence of viral genomes. Here we summarize and review the results of this comprehensive phenotype/genotype correlation and discuss the relevance of stage-specific chromosomal aberrations with respect to diagnostic applications. JF - Genes, chromosomes & cancer AU - Ried, T AU - Heselmeyer-Haddad, K AU - Blegen, H AU - Schröck, E AU - Auer, G AD - National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 195 EP - 204 VL - 25 IS - 3 SN - 1045-2257, 1045-2257 KW - Index Medicus KW - Phenotype KW - Genotype KW - Neoplasm Invasiveness KW - Humans KW - Disease Progression KW - Neoplasms -- pathology KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69842772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Genomic+changes+defining+the+genesis%2C+progression%2C+and+malignancy+potential+in+solid+human+tumors%3A+a+phenotype%2Fgenotype+correlation.&rft.au=Ried%2C+T%3BHeselmeyer-Haddad%2C+K%3BBlegen%2C+H%3BSchr%C3%B6ck%2C+E%3BAuer%2C+G&rft.aulast=Ried&rft.aufirst=T&rft.date=1999-07-01&rft.volume=25&rft.issue=3&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of a recombination reporter insert to define meiotic recombination domains on chromosome III of Saccharomyces cerevisiae. AN - 69832125; 10373533 AB - In Saccharomyces cerevisiae, meiotic recombination is initiated by DNA double-strand breaks (DSBs). DSBs usually occur in intergenic regions that display nuclease hypersensitivity in digests of chromatin. DSBs are distributed nonuniformly across chromosomes; on chromosome III, DSBs are concentrated in two "hot" regions, one in each chromosome arm. DSBs occur rarely in regions within about 40 kb of each telomere and in an 80-kb region in the center of the chromosome, just to the right of the centromere. We used recombination reporter inserts containing arg4 mutant alleles to show that the "cold" properties of the central DSB-deficient region are imposed on DNA inserted in the region. Cold region inserts display DSB and recombination frequencies that are substantially less than those seen with similar inserts in flanking hot regions. This occurs without apparent change in chromatin structure, as the same pattern and level of DNase I hypersensitivity is seen in chromatin of hot and cold region inserts. These data are consistent with the suggestion that features of higher-order chromosome structure or chromosome dynamics act in a target sequence-independent manner to control where recombination events initiate during meiosis. JF - Molecular and cellular biology AU - Borde, V AU - Wu, T C AU - Lichten, M AD - Laboratory of Biochemistry, Division of Basic Science, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 4832 EP - 4842 VL - 19 IS - 7 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - Deoxyribonuclease I KW - EC 3.1.21.1 KW - Arg4 protein, S cerevisiae KW - EC 4.3.2.1 KW - Argininosuccinate Lyase KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - Index Medicus KW - Genes, Reporter KW - Crossing Over, Genetic KW - Fungal Proteins -- genetics KW - Mutagenesis, Insertional KW - Binding Sites KW - Saccharomyces cerevisiae -- genetics KW - Recombination, Genetic KW - Meiosis -- genetics KW - Chromosomes, Fungal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69832125?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Use+of+a+recombination+reporter+insert+to+define+meiotic+recombination+domains+on+chromosome+III+of+Saccharomyces+cerevisiae.&rft.au=Borde%2C+V%3BWu%2C+T+C%3BLichten%2C+M&rft.aulast=Borde&rft.aufirst=V&rft.date=1999-07-01&rft.volume=19&rft.issue=7&rft.spage=4832&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-22 N1 - Date created - 1999-07-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Annu Rev Biochem. 1989;58:351-75 [2549853] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):87-9 [9419331] Cell. 1990 May 4;61(3):419-36 [2185891] Cell. 1990 Jun 15;61(6):1089-101 [2190690] Methods Enzymol. 1991;194:182-7 [2005786] Mol Cell Biol. 1991 Oct;11(10):4973-84 [1656219] Science. 1992 Apr 10;256(5054):228-32 [1566070] Proc Natl Acad Sci U S A. 1992 May 1;89(9):4062-5 [1570334] Nature. 1992 May 7;357(6373):38-46 [1574125] J Biol Chem. 1992 Jul 5;267(19):13150-3 [1320012] EMBO J. 1992 Sep;11(9):3441-7 [1324174] Yeast. 1992 Oct;8(10):817-902 [1413997] Mol Cell Biol. 1993 Jan;13(1):373-82 [8417336] J Mol Biol. 1993 Mar 20;230(2):413-24 [8464057] Genetics. 1993 May;134(1):175-88 [8514126] Science. 1994 Jan 28;263(5146):515-8 [8290959] Genetics. 1994 Mar;136(3):953-64 [8005447] EMBO J. 1994 Dec 1;13(23):5754-63 [7988571] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11929-33 [7991559] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11934-7 [7991560] J Bacteriol. 1974 Apr;118(1):8-14 [4595206] Annu Rev Genet. 1976;10:53-134 [797314] Genetics. 1985 Jun;110(2):187-216 [3891509] Science. 1986 Nov 7;234(4777):713-7 [3535068] Genetics. 1986 Nov;114(3):769-89 [3539697] Genetics. 1987 Feb;115(2):233-46 [3549449] Cell. 1988 Mar 25;52(6):863-73 [3280137] Annu Rev Biochem. 1988;57:159-97 [3052270] Mol Cell Biol. 1995 Mar;15(3):1679-88 [7862159] Genetics. 1995 May;140(1):55-66 [7635308] EMBO J. 1995 Sep 15;14(18):4599-608 [7556103] Am J Hum Genet. 1995 Oct;57(4):867-74 [7573048] EMBO J. 1995 Oct 16;14(20):5115-28 [7588640] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10450-6 [7479818] Mol Cell Biol. 1996 May;16(5):2037-43 [8628269] EMBO J. 1996 Mar 15;15(6):1451-9 [8635478] Biochemistry. 1996 May 7;35(18):5787-95 [8639539] Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7131-6 [8692957] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8167-74 [8710842] Genetics. 1996 Jan;142(1):79-89 [8770586] Annu Rev Genet. 1995;29:423-44 [8825482] Hum Mol Genet. 1996;5 Spec No:1495-504 [8875256] Genetics. 1996 Sep;144(1):43-55 [8878672] Yeast. 1996 Mar 15;12(3):259-65 [8904338] Chromosoma. 1996 Dec;105(5):276-84 [8939820] Nat Genet. 1996 Dec;14(4):400-5 [8944019] Science. 1997 Jan 31;275(5300):632-7 [9005842] EMBO J. 1997 Jan 2;16(1):193-202 [9009280] Genetics. 1997 Mar;145(3):661-70 [9055076] Genes Cells. 1996 May;1(5):475-89 [9078379] Proc Natl Acad Sci U S A. 1997 May 13;94(10):5213-8 [9144217] Genetics. 1997 Jul;146(3):781-95 [9215887] Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):646-51 [9435246] Science. 1998 Feb 6;279(5352):876-8 [9452390] Curr Opin Genet Dev. 1998 Apr;8(2):200-11 [9610411] Cell. 1998 Aug 7;94(3):387-98 [9708740] Mol Cell Biol. 1998 Sep;18(9):5392-403 [9710623] Genes Dev. 1998 Sep 15;12(18):2932-42 [9744869] Curr Biol. 1998 Oct 8;8(20):1095-101 [9778527] J Cell Sci. 1999 Mar;112 ( Pt 5):651-8 [9973600] Genetics. 1997 Jul;146(3):797-816 [9215888] Hum Mol Genet. 1997 Sep;6(9):1391-9 [9285774] Genes Dev. 1997 Oct 15;11(20):2600-21 [9334324] Mol Cell Biol. 1989 Oct;9(10):4488-94 [2685553] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification and rapid quantification of early- and late-lytic human herpesvirus 8 infection in single cells by flow cytometric analysis: characterization of antiherpesvirus agents. AN - 69823414; 10364341 AB - Human herpesvirus 8 (HHV-8) infection is associated with Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. In this study, we used monoclonal antibodies (MAbs) directed against HHV-8 lytic cycle-associated proteins encoded by open reading frame (ORF) 59 (nuclear PF-8 protein) and ORF K8.1 (viral envelope glycoprotein K8.1 [gpK8.1]) to investigate HHV-8 lytic infection in single cells. Lytically infected cells were labeled with MAbs, stained with fluorescently conjugated secondary Abs, and analyzed by flow cytometry. A 3-day stimulation of HHV-8-positive PEL cell lines (BCBL-1 and BC-3) with 12-O-tetradecanoylphorbol-13-acetate (30 nM) or n-butyric acid (0.3 mM) maximized the expression of lytic-phase viral proteins and minimized cell toxicity. The absolute number of expressing cells was inducer and cell line dependent. Expression of PF-8 occurred earlier and more frequently (in up to 20% of cells) than did expression of gpK8.1. A subset of PF-8 positive cells (25%) co-expressed gpK8.1, representing the majority of gpK8.1 expressing cells. Acyclovir, foscarnet, cidofovir, and PMEA reduced the number of cells expressing gpK8.1, but not the number expressing the nonstructural early lytic gene product PF-8. By contrast, alpha interferon (IFN-alpha) and IFN-beta reduced expression of both PF-8 and gpK8.1, implying an overall inhibitory effect on viral gene transcription or translation. In summary, we have characterized and quantified HHV-8 lytic infection in single cells by dual measurement of early- and late-lytic-cycle HHV-8 protein expression. This technique should prove useful for screening of possible antiherpesvirus agents and for detailed phenotypic characterization of HHV-8-infected cells in vitro and in patients with HHV-8-associated diseases. JF - Journal of virology AU - Zoeteweij, J P AU - Eyes, S T AU - Orenstein, J M AU - Kawamura, T AU - Wu, L AU - Chandran, B AU - Forghani, B AU - Blauvelt, A AD - Dermatology Branch, National Cancer Institute,National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 5894 EP - 5902 VL - 73 IS - 7 SN - 0022-538X, 0022-538X KW - Antiviral Agents KW - 0 KW - Glycoproteins KW - Interferon-alpha KW - K8.1 protein, Human herpesvirus 8 KW - ORF59 protein, Human herpesvirus 8 KW - Viral Proteins KW - Foscarnet KW - 364P9RVW4X KW - Interferon-beta KW - 77238-31-4 KW - Interferon-gamma KW - 82115-62-6 KW - Acyclovir KW - X4HES1O11F KW - Index Medicus KW - AIDS/HIV KW - Interferon-alpha -- pharmacology KW - Blotting, Western KW - Interferon-beta -- pharmacology KW - Acyclovir -- pharmacology KW - Fluorescent Antibody Technique, Indirect KW - Humans KW - Interferon-gamma -- pharmacology KW - Foscarnet -- pharmacology KW - Microscopy, Electron KW - Flow Cytometry KW - Time Factors KW - Cell Line KW - Herpesvirus 8, Human -- ultrastructure KW - Herpesvirus 8, Human -- drug effects KW - Herpesvirus 8, Human -- metabolism KW - Antiviral Agents -- pharmacology KW - Viral Proteins -- biosynthesis KW - Herpesvirus 8, Human -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69823414?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+and+rapid+quantification+of+early-+and+late-lytic+human+herpesvirus+8+infection+in+single+cells+by+flow+cytometric+analysis%3A+characterization+of+antiherpesvirus+agents.&rft.au=Zoeteweij%2C+J+P%3BEyes%2C+S+T%3BOrenstein%2C+J+M%3BKawamura%2C+T%3BWu%2C+L%3BChandran%2C+B%3BForghani%2C+B%3BBlauvelt%2C+A&rft.aulast=Zoeteweij&rft.aufirst=J&rft.date=1999-07-01&rft.volume=73&rft.issue=7&rft.spage=5894&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-23 N1 - Date created - 1999-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Infect Dis. 1996 Jun;173(6):1477-80 [8648224] J Virol. 1998 Aug;72(8):6725-31 [9658120] Blood. 1996 Jul 1;88(1):297-301 [8704186] J Exp Med. 1996 Jul 1;184(1):283-8 [8691144] Blood. 1996 Oct 1;88(7):2648-54 [8839859] AIDS. 1996 Sep;10(10):1101-5 [8874626] J Virol. 1996 Nov;70(11):8218-23 [8892957] J Infect Dis. 1996 Nov;174(5):1101-5 [8896516] Science. 1996 Dec 6;274(5293):1739-44 [8939871] Am J Pathol. 1997 Jan;150(1):147-53 [9006331] Lancet. 1997 Jan 25;349(9047):255 [9014921] J Virol. 1997 May;71(5):3420-30 [9094612] AIDS. 1997 Apr;11(5):F35-45 [9108935] J Clin Invest. 1997 May 1;99(9):2082-6 [9151779] J Infect Dis. 1997 Aug;176(2):541 [9237728] AIDS. 1997 Sep;11(11):1327-32 [9302441] AIDS Res Hum Retroviruses. 1997 Sep 20;13(14):1229-33 [9310290] J Virol. 1997 Oct;71(10):7963-8 [9311888] Virology. 1998 Sep 15;249(1):140-9 [9740785] J Acquir Immune Defic Syndr Hum Retrovirol. 1999 Jan 1;20(1):34-8 [9928727] J Gen Virol. 1999 Jan;80 ( Pt 1):83-90 [9934688] Adv Dermatol. 1999;14:167-206; discussion 207 [10643499] J Virol. 1992 Jul;66(7):4126-33 [1318399] Virology. 1994 May 1;200(2):447-56 [8178434] Science. 1994 Dec 16;266(5192):1865-9 [7997879] Science. 1995 Feb 24;267(5201):1078-9 [7855583] N Engl J Med. 1995 May 4;332(18):1181-5 [7700310] N Engl J Med. 1995 May 4;332(18):1186-91 [7700311] Science. 1995 Apr 28;268(5210):582-3 [7725108] Blood. 1995 Aug 15;86(4):1276-80 [7632932] Lancet. 1995 Aug 26;346(8974):578 [7658802] Blood. 1995 Oct 1;86(7):2708-14 [7670109] Lancet. 1995 Sep 23;346(8978):799-802 [7674745] J Virol. 1996 Jan;70(1):549-58 [8523568] Nat Med. 1996 Mar;2(3):342-6 [8612236] Antimicrob Agents Chemother. 1997 Dec;41(12):2754-6 [9420052] J Virol. 1998 Feb;72(2):1005-12 [9444993] Virology. 1998 Jan 5;240(1):118-26 [9448696] J Virol. 1998 Jul;72(7):6228-32 [9621095] J Exp Med. 1996 May 1;183(5):2385-90 [8642350] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion. AN - 69823029; 10364363 AB - We have examined mutations in the ectodomain of the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 within a region immediately adjacent to the membrane-spanning domain for their effect on the outcome of the fusion cascade. Using the recently developed three-color assay (I. Muñoz-Barroso, S. Durell, K. Sakaguchi, E. Appella, and R. Blumenthal, J. Cell Biol. 140:315-323, 1998), we have assessed the ability of the mutant gp41s to transfer lipid and small solutes from susceptible target cells to the gp120-gp41-expressing cells. The results were compared with the syncytium-inducing capabilities of these gp41 mutants. Two mutant proteins were incapable of mediating both dye transfer and syncytium formation. Two mutant proteins mediated dye transfer but were less effective at inducing syncytium formation than was wild-type gp41. The most interesting mutant proteins were those that were not capable of inducing syncytium formation but still mediated dye transfer, indicating that the fusion cascade was blocked beyond the stage of small fusion pore formation. Fusion mediated by the mutant gp41s was inhibited by the peptides DP178 and C34. JF - Journal of virology AU - Muñoz-Barroso, I AU - Salzwedel, K AU - Hunter, E AU - Blumenthal, R AD - Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 6089 EP - 6092 VL - 73 IS - 7 SN - 0022-538X, 0022-538X KW - HIV Envelope Protein gp120 KW - 0 KW - HIV Envelope Protein gp41 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Cell Membrane -- virology KW - COS Cells KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Mutagenesis KW - Binding Sites KW - HIV-1 -- metabolism KW - HIV-1 -- genetics KW - Membrane Fusion KW - HIV Envelope Protein gp41 -- metabolism KW - HIV Envelope Protein gp41 -- genetics KW - HIV Envelope Protein gp120 -- metabolism KW - HIV Envelope Protein gp120 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69823029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Role+of+the+membrane-proximal+domain+in+the+initial+stages+of+human+immunodeficiency+virus+type+1+envelope+glycoprotein-mediated+membrane+fusion.&rft.au=Mu%C3%B1oz-Barroso%2C+I%3BSalzwedel%2C+K%3BHunter%2C+E%3BBlumenthal%2C+R&rft.aulast=Mu%C3%B1oz-Barroso&rft.aufirst=I&rft.date=1999-07-01&rft.volume=73&rft.issue=7&rft.spage=6089&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-23 N1 - Date created - 1999-07-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1986 Jul;59(1):181-4 [2423703] J Virol. 1999 Mar;73(3):2469-80 [9971832] J Biol Chem. 1993 May 5;268(13):9267-74 [8387488] Cell. 1993 May 21;73(4):823-32 [8500173] Cell. 1994 Jan 28;76(2):383-91 [8293471] Nature. 1994 Sep 1;371(6492):37-43 [8072525] J Cell Biol. 1996 Oct;135(1):63-71 [8858163] Cell. 1997 Apr 18;89(2):263-73 [9108481] Nature. 1997 May 22;387(6631):426-30 [9163431] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8 [9356444] J Biol Chem. 1998 Jan 2;273(1):404-9 [9417096] J Virol. 1998 Feb;72(2):986-93 [9444991] J Cell Biol. 1998 Jan 26;140(2):315-23 [9442107] Virology. 1998 Sep 1;248(2):284-94 [9721237] J Virol. 1992 Apr;66(4):2232-9 [1548759] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Occupational cancer among women: research status and methodologic considerations. AN - 69811375; 10361581 AB - Occupational causes of cancer have not been well-evaluated among women. An increase in the number of women in the work force in jobs with potentially hazardous exposures during the past few decades raises the question as to whether there is a need to enhance our efforts in this area. The inability to evaluate occupational causes of female gynecologic tumors in studies of men, plus the potential for variation in outcome responses between men and women because of gender-based exposure and susceptibility differences, underscore the need for investigations specifically focused on women. Investigations of occupational exposures and cancer risk among women may require design considerations that differ somewhat from studies of men. Issues to consider include the impact of studying outcomes with high survival (e.g., breast cancer), gender-specific exposure patterns and toxicokinetic processing of some chemicals, special limitations in the use of the general population as the referent, and the need to control for established risk factors for gynecologic tumors. JF - American journal of industrial medicine AU - Blair, A AU - Zahm, S H AU - Silverman, D T AD - National Cancer Institute, Occupational Epidemiology Branch, Bethesda, Maryland, USA. blaira@epndce.nci.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 6 EP - 17 VL - 36 IS - 1 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Sex Factors KW - Humans KW - Cohort Studies KW - Developed Countries KW - Male KW - Female KW - Occupational Exposure -- statistics & numerical data KW - Women's Health KW - Women, Working -- statistics & numerical data KW - Neoplasms -- epidemiology KW - Research Design -- standards KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69811375?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Occupational+cancer+among+women%3A+research+status+and+methodologic+considerations.&rft.au=Blair%2C+A%3BZahm%2C+S+H%3BSilverman%2C+D+T&rft.aulast=Blair&rft.aufirst=A&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=6&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-15 N1 - Date created - 1999-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gender differences in risk of renal cell carcinoma and occupational exposures to chlorinated aliphatic hydrocarbons. AN - 69807983; 10361587 AB - Organic solvents have been associated with renal cell cancer; however, the risk by gender and type of solvents is nuclear. We evaluated the risk of renal cell carcinoma among men and women exposed to all organic solvents-combined, all chlorinated aliphatic hydrocarbons (CAHC)-combined, and nine individual CAHC using a priori job exposure matrices developed by NCI in a population-based case-control study in Minnesota, U.S. We interviewed 438 renal cell cancer cases (273 men and 165 women) and 687 controls (462 men and 225 women). Overall, 34% of male cases and 21% of female cases were exposed to organic solvents in general. The risk of renal cell carcinoma was significantly elevated among women exposed to all organic solvents combined (OR = 2.3; 95% CI = 1.3-4.2), to CAHC combined (OR = 2.1; 95% CI = 1.1-3.9), and to trichloroethylene (TCE) (OR = 2.0; 95% CI = 1.0-4.0). Among men, no significant excess risk was observed among men exposed to any of these nine individual CAHCs, all CAHCs-combined, or all organic solvents-combined. These observed gender differences in risk of renal cell carcinoma in relation to exposure to organic solvents may be explained by chance based on small numbers, or by the differences in body fat content, metabolic activity, the rate of elimination of xenobiotics from the body, or by differences in the level of exposure between men and women, even though they have the same job title. JF - American journal of industrial medicine AU - Dosemeci, M AU - Cocco, P AU - Chow, W H AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. dosemecm@epndce.nci.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 54 EP - 59 VL - 36 IS - 1 SN - 0271-3586, 0271-3586 KW - Hydrocarbons, Chlorinated KW - 0 KW - Solvents KW - Index Medicus KW - Odds Ratio KW - Sex Factors KW - Disease Susceptibility -- epidemiology KW - Humans KW - Aged KW - Aged, 80 and over KW - Logistic Models KW - Adult KW - Case-Control Studies KW - Confidence Intervals KW - Occupations -- statistics & numerical data KW - Middle Aged KW - Occupations -- classification KW - Female KW - Male KW - Minnesota -- epidemiology KW - Occupational Exposure -- statistics & numerical data KW - Carcinoma, Renal Cell -- chemically induced KW - Kidney Neoplasms -- chemically induced KW - Solvents -- adverse effects KW - Occupational Exposure -- adverse effects KW - Occupational Diseases -- epidemiology KW - Kidney Neoplasms -- epidemiology KW - Hydrocarbons, Chlorinated -- adverse effects KW - Occupational Diseases -- chemically induced KW - Carcinoma, Renal Cell -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Gender+differences+in+risk+of+renal+cell+carcinoma+and+occupational+exposures+to+chlorinated+aliphatic+hydrocarbons.&rft.au=Dosemeci%2C+M%3BCocco%2C+P%3BChow%2C+W+H&rft.aulast=Dosemeci&rft.aufirst=M&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=54&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-15 N1 - Date created - 1999-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality in women with probable exposure to silica: a death certificate study in 24 states of the U.S. AN - 69807692; 10361596 AB - Silica exposure is known to cause an increased risk of pneumoconiosis and some types of cancers. Exposure to silica is becoming an increasingly common occupational hazard for women. Studies contradict each other on whether or not women suffer more occupational pneumoconiosis than men, but no studies have evaluated cancer risks among women exposed to silica. Death certificate data on occupation and industry from 24 states in the U.S. between 1984 and 1993 were used to calculate proportional mortality ratios (PMRs) for workers exposed to silica. Over 20,000 deaths (4% of all deaths in persons with possible work-related silica-exposure) occurred among women. The PMR for pneumoconiosis among women working in occupations or industries with possible silica exposure was 13.6 (95% CI: 7.2-23.2), for men 3.8 (CI: 3.7-4.0). Both men and women had higher than expected PMRs for respiratory diseases, lung and esophageal cancers, and external causes of death. In the group with probable silica exposure (both occupation and industry associated with silica), women had elevated PMRs for thyroid cancer (PMR = 5.5), multiple myeloma (PMR = 1.3), digestive organ cancers (PMR = 1.2), whereas men had no increased PMRs for these cancers. Both genders had significantly decreased PMRs for breast cancer, cerebrovascular diseases, nervous system diseases, and brain and other central nervous system cancers. An in depth look at the types of silica exposures (specific work duties) and adjustment for confounders is warranted to determine the importance of these gender-specific excess mortalities associated with possible silica exposure. JF - American journal of industrial medicine AU - Fillmore, C M AU - Petralia, S A AU - Dosemeci, M AD - Occupational Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20892-7240, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 122 EP - 128 VL - 36 IS - 1 SN - 0271-3586, 0271-3586 KW - Silicon Dioxide KW - 7631-86-9 KW - Index Medicus KW - Sex Factors KW - Women's Health KW - Humans KW - Respiratory Tract Diseases -- etiology KW - Cohort Studies KW - Retrospective Studies KW - Occupations -- statistics & numerical data KW - Statistics as Topic KW - Respiratory Tract Diseases -- mortality KW - Occupations -- classification KW - United States -- epidemiology KW - Male KW - Female KW - Cause of Death KW - Occupational Exposure -- statistics & numerical data KW - Neoplasms -- mortality KW - Neoplasms -- chemically induced KW - Death Certificates KW - Occupational Diseases -- etiology KW - Occupational Exposure -- adverse effects KW - Silicon Dioxide -- adverse effects KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807692?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+mortality+in+women+with+probable+exposure+to+silica%3A+a+death+certificate+study+in+24+states+of+the+U.S.&rft.au=Fillmore%2C+C+M%3BPetralia%2C+S+A%3BDosemeci%2C+M&rft.aulast=Fillmore&rft.aufirst=C&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=122&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-15 N1 - Date created - 1999-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer mortality among women employed in health care occupations in 24 U.S. states, 1984-1993. AN - 69807663; 10361602 AB - Health care workers are potentially exposed to a number of carcinogens. Studies among women in this field have focused on white nurses; however, workers in many health care occupations share exposures experienced by nurses. Cancer mortality was examined among female health care workers using death certificate data collected in 24 U.S. states from 1984 through 1993. Cancer mortality odds ratios (MORs) were calculated by race (white, black) and age group. White nurses had a 30% elevation of mortality due to liver cancer and myeloid leukemia. White registered nurses (RNs) had a small excess and white licensed practical nurses (LPNs) had a small deficit of mortality due to breast cancer. Ovarian cancer was in excess among RNs, but decreased among LPNs. Among black nurses, excesses of death due to kidney cancer (MOR = 1.7) and multiple myeloma (MOR = 1.3), and a significant 50% deficit in mortality due to cancer of the esophagus were found. Black RNs, but not LPNs, had an excess of breast cancer (MOR = 1.3; 95% CI = 1.0-1.5). Ovarian cancer was elevated by 30% in both RNs and LPNs. Excess deaths due to cancers of the breast, ovary, and uterus occurred among white physicians. Among black physicians, lung cancer was significantly elevated (MOR = 2.8). White pharmacists had significant excesses of breast (MOR = 1.5) and ovarian (MOR = 2.4) cancers, and myeloid leukemia (MOR = 2.0). White clinical laboratory technicians had excess deaths from several cancers. The greatest excess was for myeloid leukemia (MOR = 2.3; 95% CI = 1.5-3.4). Excesses among radiologic technologists included cancers of the lung, pancreas, breast, uterus, and ovary. Several findings reported here warrant further investigation. In particular, excesses of myeloid leukemia among nurses, pharmacists, and clinical laboratory technicians and liver cancer among nurses should be investigated in studies with data on occupational and other exposures. Patterns of mortality from breast and ovarian cancer found in this study must be evaluated further in studies with data on reproductive history. JF - American journal of industrial medicine AU - Petralia, S A AU - Dosemeci, M AU - Adams, E E AU - Zahm, S H AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20892, USA. sp126i@nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 159 EP - 165 VL - 36 IS - 1 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Odds Ratio KW - Women's Health KW - Humans KW - Death Certificates KW - African Americans -- statistics & numerical data KW - Adult KW - Retrospective Studies KW - European Continental Ancestry Group -- statistics & numerical data KW - Confidence Intervals KW - Aged KW - Middle Aged KW - United States -- epidemiology KW - Female KW - Age Distribution KW - Health Personnel -- statistics & numerical data KW - Neoplasms -- mortality KW - Caregivers -- statistics & numerical data KW - Neoplasms -- etiology KW - Occupational Diseases -- mortality UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Cancer+mortality+among+women+employed+in+health+care+occupations+in+24+U.S.+states%2C+1984-1993.&rft.au=Petralia%2C+S+A%3BDosemeci%2C+M%3BAdams%2C+E+E%3BZahm%2C+S+H&rft.aulast=Petralia&rft.aufirst=S&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-15 N1 - Date created - 1999-09-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Preceding infection as a risk factor of stroke in the young. AN - 69474568; 10778584 AB - The cause of stroke in the young remains unknown in 20-50% of the patients. Infections preceding stroke have been recently recognised to be an independent risk factor of stroke. Sixty consecutive patients aged 40 years or less presenting with ischaemic completed stroke are taken up for the study. Patients with neurological deficit of less than 24 hours, evidence of haemorrhage on CT scan, infection occurring after the onset of stroke were excluded. Controls consisted of age and sex matched persons residing in the same area. Both the groups were enquired about preceding fever and infections and were examined for evidence of infections. Serum was examined for antibodies against measles, herpes simplex, and Japanese B encephalitis viruses. Cultures were put up from appropriate samples and CSF examined in patients only. Evidence of infection was noted in 26 (43.3%) of patients and 6 controls (p < 0.001). History of fever was elicited in 23 patients and 3 controls while 15 patients were febrile on examination at admission. Signs of local infection was observed in 14 patients and one control. The commonest site of infection was respiratory tract. Cultures were positive in 11 patients, commonest being beta haemolytic streptococci in six from throat. Conventional risk factors were identical in both groups of patients with and without evidence of preceding infection. Smoking and alcoholism were significantly higher in patients with preceding infection. Preceding infection is an important risk factor of stroke in the young. Smoking and alcoholism are more frequent in patients with preceding infection. Whether they predispose the individual for infection or infection increases the stroke risk in them needs to be examined. JF - The Journal of the Association of Physicians of India AU - Nagaraja, D AU - Christopher, R AU - Tripathi, M AU - Kumar, M V AU - Valli, E R AU - Patil, S A AD - Dept. of Neurology, National Institute of Mental Health and Neurosciences, Bangalore. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 673 EP - 675 VL - 47 IS - 7 SN - 0004-5772, 0004-5772 KW - Index Medicus KW - Alcoholism -- epidemiology KW - Risk Factors KW - Humans KW - Respiratory Tract Infections -- epidemiology KW - Adult KW - Case-Control Studies KW - Streptococcal Infections -- epidemiology KW - Smoking -- epidemiology KW - Male KW - Female KW - Stroke -- epidemiology KW - Stroke -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69474568?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+the+Association+of+Physicians+of+India&rft.atitle=Preceding+infection+as+a+risk+factor+of+stroke+in+the+young.&rft.au=Nagaraja%2C+D%3BChristopher%2C+R%3BTripathi%2C+M%3BKumar%2C+M+V%3BValli%2C+E+R%3BPatil%2C+S+A&rft.aulast=Nagaraja&rft.aufirst=D&rft.date=1999-07-01&rft.volume=47&rft.issue=7&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+the+Association+of+Physicians+of+India&rft.issn=00045772&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-06 N1 - Date created - 2000-06-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SR 141716A, a CB1 cannabinoid receptor antagonist, potentiates the locomotor stimulant effects of amphetamine and apomorphine. AN - 69471922; 10780811 AB - The intraperitoneal (i.p.) injection of apomorphine or d-amphetamine significantly increased locomotor activity in Sprague-Dawley rats. Prior administration of the cannabinoid receptor antagonist, SR 141716A, significantly enhanced the stimulant effect of both d-amphetamine and apomorphine in a dose-dependent manner. Administration of SR 141716A alone had no effect on locomotor activity. These data indicate that endogenous cannabinoids exert an inhibitory action on the increase in locomotor activity produced by amphetamine and apomorphine. JF - Behavioural pharmacology AU - Masserano, J M AU - Karoum, F AU - Wyatt, R J AD - National Institute of Mental Health, Neuropsychiatry Branch, Bethesda, Maryland 20892-2668, USA. MASSERAJ@intra.nimh.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 429 EP - 432 VL - 10 IS - 4 SN - 0955-8810, 0955-8810 KW - Central Nervous System Stimulants KW - 0 KW - Dopamine Agonists KW - Piperidines KW - Pyrazoles KW - Receptors, Cannabinoid KW - Receptors, Drug KW - Amphetamine KW - CK833KGX7E KW - Apomorphine KW - N21FAR7B4S KW - rimonabant KW - RML78EN3XE KW - Index Medicus KW - Rats KW - Injections, Intraperitoneal KW - Animals KW - Rats, Sprague-Dawley KW - Dose-Response Relationship, Drug KW - Drug Synergism KW - Male KW - Piperidines -- pharmacology KW - Apomorphine -- administration & dosage KW - Pyrazoles -- pharmacology KW - Central Nervous System Stimulants -- pharmacology KW - Dopamine Agonists -- pharmacology KW - Apomorphine -- pharmacology KW - Amphetamine -- administration & dosage KW - Motor Activity -- drug effects KW - Dopamine Agonists -- administration & dosage KW - Central Nervous System Stimulants -- administration & dosage KW - Amphetamine -- pharmacology KW - Receptors, Drug -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69471922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioural+pharmacology&rft.atitle=SR+141716A%2C+a+CB1+cannabinoid+receptor+antagonist%2C+potentiates+the+locomotor+stimulant+effects+of+amphetamine+and+apomorphine.&rft.au=Masserano%2C+J+M%3BKaroum%2C+F%3BWyatt%2C+R+J&rft.aulast=Masserano&rft.aufirst=J&rft.date=1999-07-01&rft.volume=10&rft.issue=4&rft.spage=429&rft.isbn=&rft.btitle=&rft.title=Behavioural+pharmacology&rft.issn=09558810&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-05-24 N1 - Date created - 2000-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - MUC1 upregulation by ethanol. AN - 69462419; 10738897 AB - MUC1 is a glycoprotein and its expression is altered in breast cancer. Mucin protects epithelia from the external hostile environment. The expression of mucin changes when epithelia come in contact with toxic agents such as ethanol. Previously, we characterized the expression and regulation of tracheo-bronchial mucin (TBM) gene. In the present study, we studied the effect of ethanol on the gene encoding mammary gland mucin MUC1 and observed that ethanol regulates MUC1 expression at the transcription level. Ethanol enhanced the expression of MUC1 mRNA in a dose- and time-dependent manner in MCF-7 cells. At 100 mM concentration (a concentration reported to be present in alcoholics), ethanol induced a three to five-fold increase in mucin transcription as determined by nuclear run on analysis. This concentration of ethanol does not affect the half-life of MUC1 mRNA. JF - Cancer biochemistry biophysics AU - Verma, M AU - Davidson, E A AD - Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA. mverma@niaid.nih.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 1 EP - 11 VL - 17 IS - 1-2 SN - 0305-7232, 0305-7232 KW - Mucin-1 KW - 0 KW - Neoplasm Proteins KW - RNA, Messenger KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Neoplasm Proteins -- biosynthesis KW - Transcription, Genetic -- drug effects KW - Tumor Cells, Cultured -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Dose-Response Relationship, Drug KW - Humans KW - Gene Expression Regulation, Neoplastic -- drug effects KW - RNA, Messenger -- biosynthesis KW - Adenocarcinoma -- pathology KW - Cell Size -- drug effects KW - Stimulation, Chemical KW - Breast Neoplasms -- pathology KW - Cell Survival -- drug effects KW - Neoplasm Proteins -- genetics KW - Tumor Cells, Cultured -- pathology KW - Female KW - Mucin-1 -- genetics KW - Ethanol -- pharmacology KW - Mucin-1 -- biosynthesis KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69462419?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+biochemistry+biophysics&rft.atitle=MUC1+upregulation+by+ethanol.&rft.au=Verma%2C+M%3BDavidson%2C+E+A&rft.aulast=Verma&rft.aufirst=M&rft.date=1999-07-01&rft.volume=17&rft.issue=1-2&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+biochemistry+biophysics&rft.issn=03057232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-02 N1 - Date created - 2000-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Successful treatment of metastatic renal cell carcinoma with a nonmyeloablative allogeneic peripheral-blood progenitor-cell transplant: evidence for a graft-versus-tumor effect. AN - 69284835; 10561256 AB - A 50-year-old man developed progressive pulmonary metastasis resistant to interferon alfa-2b treatment 7 months after he underwent left nephrectomy for stage III renal cell carcinoma. We performed a nonmyeloablative allogeneic peripheral-blood stem-cell transplant in this patient to exploit a possible graft-versus-tumor effect from allogeneic lymphocytes. The conditioning regimen consisted of fludarabine and cyclophosphamide followed by a T-cell replete, granulocyte-colony stimulating-factor-mobilized peripheral-blood stem-cell transplant from his HLA-identical brother. Cyclosporine was administered from days -4 to +45 to prevent graft rejection and acute graft-versus-host disease (GVHD). Serial polymerase chain reaction analysis of hematopoietic lineage-specific minisatellites initiallyshowed mixed chimerism in CD14(+) and CD15(+) myeloid cells, CD3(+) T cells, and CD34(+) progenitor cells, with rapid conversion to 100% donor T-cell chimerism by day +60 and 100% donor myeloid cells by day +100. Serial computed tomography scans of the chest showed stable disease at day +30, slight regression of pulmonary lesions at day +63, and complete disappearance of all pulmonary metastatic disease by day +110. Mild transient acute GVHD disease of the skin occurred on day +60 and limited chronic GVHD of the skin occurred by day +200. The complete regression of metastatic disease, which has now been maintained for more than 1 year, is compatible with a graft-versus-tumor effect. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Childs, R W AU - Clave, E AU - Tisdale, J AU - Plante, M AU - Hensel, N AU - Barrett, J AD - Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA. childsr@nihh.gov Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 2044 EP - 2049 VL - 17 IS - 7 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents KW - 0 KW - Immunosuppressive Agents KW - Cyclophosphamide KW - 8N3DW7272P KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Index Medicus KW - Vidarabine -- analogs & derivatives KW - Cyclophosphamide -- therapeutic use KW - Humans KW - Transplantation Conditioning -- methods KW - Treatment Outcome KW - Middle Aged KW - Transplantation, Homologous KW - Vidarabine -- therapeutic use KW - Antineoplastic Agents -- therapeutic use KW - Immunosuppressive Agents -- therapeutic use KW - Male KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Graft vs Tumor Effect -- immunology KW - Lung Neoplasms -- secondary KW - Hematopoietic Stem Cell Transplantation KW - Lung Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69284835?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Successful+treatment+of+metastatic+renal+cell+carcinoma+with+a+nonmyeloablative+allogeneic+peripheral-blood+progenitor-cell+transplant%3A+evidence+for+a+graft-versus-tumor+effect.&rft.au=Childs%2C+R+W%3BClave%2C+E%3BTisdale%2C+J%3BPlante%2C+M%3BHensel%2C+N%3BBarrett%2C+J&rft.aulast=Childs&rft.aufirst=R&rft.date=1999-07-01&rft.volume=17&rft.issue=7&rft.spage=2044&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. AN - 69284444; 10561265 AB - To determine the short- and long-term efficacy and toxicity of the high-dose intravenous bolus interleukin 2 (IL-2) regimen in patients with metastatic melanoma. Two hundred seventy assessable patients were entered onto eight clinical trials conducted between 1985 and 1993. IL-2 (Proleukin [aldesleukin]; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical treatment cycle was scheduled after 6 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. Data were analyzed through fall 1996. The overall objective response rate was 16% (95% confidence interval, 12% to 21%); there were 17 complete responses (CRs) (6%) and 26 partial responses (PRs) (10%). Responses occurred with all sites of disease and in patients with large tumor burdens. The median response duration for patients who achieved a CR has not been reached and was 5.9 months for those who achieved a PR. Twelve (28%) of the responding patients, including 10 (59%) of the patients who achieved a CR, remain progression-free. Disease did not progress in any patient responding for more than 30 months. Baseline performance status and whether patients had received prior systemic therapy were the only predictive prognostic factors for response to IL-2 therapy. Toxicities, although severe, generally reversed rapidly after therapy was completed. Six patients (2%) died from adverse events, all related to sepsis. High-dose IL-2 treatment seems to benefit some patients with metastatic melanoma by producing durable CRs or PRs and should be considered for appropriately selected melanoma patients. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Atkins, M B AU - Lotze, M T AU - Dutcher, J P AU - Fisher, R I AU - Weiss, G AU - Margolin, K AU - Abrams, J AU - Sznol, M AU - Parkinson, D AU - Hawkins, M AU - Paradise, C AU - Kunkel, L AU - Rosenberg, S A AD - Cytokine Working Group and Surgery Branch, National Cancer Institute, Bethesda, MD, USA. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 2105 EP - 2116 VL - 17 IS - 7 SN - 0732-183X, 0732-183X KW - Interleukin-2 KW - 0 KW - Recombinant Proteins KW - Index Medicus KW - Disease-Free Survival KW - Humans KW - Salvage Therapy KW - Aged KW - Survival Rate KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Recombinant Proteins -- adverse effects KW - Middle Aged KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - United States -- epidemiology KW - Female KW - Male KW - Recombinant Proteins -- administration & dosage KW - Interleukin-2 -- adverse effects KW - Interleukin-2 -- administration & dosage KW - Melanoma -- mortality KW - Melanoma -- secondary KW - Melanoma -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69284444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=High-dose+recombinant+interleukin+2+therapy+for+patients+with+metastatic+melanoma%3A+analysis+of+270+patients+treated+between+1985+and+1993.&rft.au=Atkins%2C+M+B%3BLotze%2C+M+T%3BDutcher%2C+J+P%3BFisher%2C+R+I%3BWeiss%2C+G%3BMargolin%2C+K%3BAbrams%2C+J%3BSznol%2C+M%3BParkinson%2C+D%3BHawkins%2C+M%3BParadise%2C+C%3BKunkel%2C+L%3BRosenberg%2C+S+A&rft.aulast=Atkins&rft.aufirst=M&rft.date=1999-07-01&rft.volume=17&rft.issue=7&rft.spage=2105&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bicalutamide monotherapy versus flutamide plus goserelin in prostate cancer patients: results of an Italian Prostate Cancer Project study. AN - 69284388; 10561254 AB - To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer. Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function. A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity. Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Boccardo, F AU - Rubagotti, A AU - Barichello, M AU - Battaglia, M AU - Carmignani, G AU - Comeri, G AU - Conti, G AU - Cruciani, G AU - Dammino, S AU - Delliponti, U AU - Ditonno, P AU - Ferraris, V AU - Lilliu, S AU - Montefiore, F AU - Portoghese, F AU - Spano, G AD - Department of Medical Oncology and Biostatistics Unit, University and National Cancer Institute, Genoa, Italy. Y1 - 1999/07// PY - 1999 DA - July 1999 SP - 2027 EP - 2038 VL - 17 IS - 7 SN - 0732-183X, 0732-183X KW - Anilides KW - 0 KW - Antineoplastic Agents KW - Antineoplastic Agents, Hormonal KW - Nitriles KW - Tosyl Compounds KW - Goserelin KW - 0F65R8P09N KW - Flutamide KW - 76W6J0943E KW - bicalutamide KW - A0Z3NAU9DP KW - Index Medicus KW - Goserelin -- administration & dosage KW - Disease-Free Survival KW - Consumer Product Safety KW - Humans KW - Disease Progression KW - Quality of Life KW - Aged KW - Erectile Dysfunction -- epidemiology KW - Erectile Dysfunction -- chemically induced KW - Survival Rate KW - Aged, 80 and over KW - Adult KW - Antineoplastic Agents, Hormonal -- administration & dosage KW - Middle Aged KW - Italy -- epidemiology KW - Male KW - Proportional Hazards Models KW - Flutamide -- administration & dosage KW - Prostatic Neoplasms -- mortality KW - Anilides -- therapeutic use KW - Prostatic Neoplasms -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69284388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Bicalutamide+monotherapy+versus+flutamide+plus+goserelin+in+prostate+cancer+patients%3A+results+of+an+Italian+Prostate+Cancer+Project+study.&rft.au=Boccardo%2C+F%3BRubagotti%2C+A%3BBarichello%2C+M%3BBattaglia%2C+M%3BCarmignani%2C+G%3BComeri%2C+G%3BConti%2C+G%3BCruciani%2C+G%3BDammino%2C+S%3BDelliponti%2C+U%3BDitonno%2C+P%3BFerraris%2C+V%3BLilliu%2C+S%3BMontefiore%2C+F%3BPortoghese%2C+F%3BSpano%2C+G&rft.aulast=Boccardo&rft.aufirst=F&rft.date=1999-07-01&rft.volume=17&rft.issue=7&rft.spage=2027&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-06-07 N1 - Date created - 2000-06-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Clin Oncol. 2000 Jan;18(2):448-50 [10637263] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia AN - 17602286; 4736935 AB - We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (ICAM-1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gram-negative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 (1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 (1 mg/kg sc, q 12 h x 3) were compared against similarly administered placebo proteins in rats challenged with intrabronchial Escherichia coli. After challenge, all animals were treated with antibiotics. ICAM-1 MAb (6 mg/kg, iv, total dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cells and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAb increased these measures compared with control from 6 to 12 h after E. coli. However, from 144 to 168 h after E. coli both MAbs increased these measures compared with control rats but to a greater level with CD11b MAb. Thus both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammation and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult. JF - Journal of Applied Physiology AU - Zeni, F AU - Parent, C AU - Correa, R AU - Natanson, C AU - Freeman, B AU - Fontana, J AU - Quezado, M AU - Danner, R L AU - Fitz, Y AU - Richmond, S AU - Gerstenberger, E AU - Banks, S M AU - Eichacker, P Q AD - Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892-1662, USA Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 299 EP - 307 VL - 87 IS - 1 SN - 8750-7587, 8750-7587 KW - rats KW - intercellular adhesion molecule 1 KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Antibiotics KW - Pneumonia KW - J 02845:Ear, nose and respiratory tract UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17602286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Physiology&rft.atitle=ICAM-1+and+CD11b+inhibition+worsen+outcome+in+rats+with+E.+coli+pneumonia&rft.au=Zeni%2C+F%3BParent%2C+C%3BCorrea%2C+R%3BNatanson%2C+C%3BFreeman%2C+B%3BFontana%2C+J%3BQuezado%2C+M%3BDanner%2C+R+L%3BFitz%2C+Y%3BRichmond%2C+S%3BGerstenberger%2C+E%3BBanks%2C+S+M%3BEichacker%2C+P+Q&rft.aulast=Zeni&rft.aufirst=F&rft.date=1999-07-01&rft.volume=87&rft.issue=1&rft.spage=299&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Physiology&rft.issn=87507587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Antibiotics; Pneumonia ER - TY - JOUR T1 - HIV and HCV infection among drug users in Japan AN - 17464146; 4669914 AB - Aims. To assess seroprevalence of human immunodeficiency virus (HIV), hepatitis C virus, injecting drug use, unsafe sexual behaviours, self-mutilation and tattoos in patients attending a drug and alcohol treatment centre in Japan. Design. Cross-sectional survey. Setting. The work was carried out at the National Sanitarium of Shimousa, Chiba, Japan, a 32-bed inpatient centre specializing in drug and alcohol treatment. Measurement. Laboratory analyses for HIV antibody, hepatitis C antibody, hepatitis B antigen and antibody; questionnaires for history of sexual activities, needle and syringe use; physical examination with assessment of self-amputated finger joints, tattoos, scars from lacerations and cigarette burns. Conclusions. HCV prevalence is a significant problem among methamphetamine users in Japan, probably because of a high rate of needle and/or syringe sharing. Although HIV infection is currently negligible, the very high rate of needle and syringe sharing could give rise to a significant increase in the HIV rate among drug users in the future. JF - Addiction AU - Wada, K AU - Greberman, S B AU - Konuma, K AU - Hirai, S AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Ichikawa-shi, Chiba 272-0827, Japan Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 1063 EP - 1070 VL - 94 IS - 7 SN - 0965-2140, 0965-2140 KW - HIV KW - Japan KW - Japan, Chiba, Shimousa KW - drug abuse KW - seroprevalence KW - sexual behavior KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Needles KW - Hepatitis C virus KW - Human immunodeficiency virus KW - Tattoos KW - Drug abuse KW - Sexual behavior KW - H 11000:Diseases/Injuries/Trauma KW - V 22005:AIDS: Epidemiological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17464146?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Addiction&rft.atitle=HIV+and+HCV+infection+among+drug+users+in+Japan&rft.au=Wada%2C+K%3BGreberman%2C+S+B%3BKonuma%2C+K%3BHirai%2C+S&rft.aulast=Wada&rft.aufirst=K&rft.date=1999-07-01&rft.volume=94&rft.issue=7&rft.spage=1063&rft.isbn=&rft.btitle=&rft.title=Addiction&rft.issn=09652140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; Hepatitis C virus; Sexual behavior; Drug abuse; Tattoos; Needles ER - TY - JOUR T1 - Parasitic Infections. Treatment and Developmental Therapeutics. 1. Necatoriasis AN - 17380060; 4600076 AB - Necator americanus is a nematode hookworm of the family Ancylostomatidae, subfamily Necatorinae. This nematode parasite, which is distinguished by two chitinous cutting plates in the buccal cavity and fused male copulatory spicules, is the causative agent of necatoriasis, a hookworm disease prevalent in the Americas as well as in the tropical regions of Africa, southern Asia, and Polynesia. The adult parasites attached to the villi of the small intestines will suck blood causing abdominal discomfort, diarrhea and cramps, anorexia, wight loss, and in advanced disease, hypochromic microcytic anemia. Hookworm infections in man, especially in children, are one of the leading causes of iron-deficiency anemia resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L sub(4)) larva and adult worms. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognized, usually self-limiting condition caused by the infectious larvae of nematodes. CLM is characterized by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm Ancylostoma braziliense is the most common causing CLM, although many other species have been implicated. JF - Current Pharmaceutical Design AU - Georgiev, V St AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 545 EP - 554 VL - 5 IS - 7 SN - 1381-6128, 1381-6128 KW - Oral cavity KW - Africa KW - Necator americanus KW - necatoriasis KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Reviews KW - Parasitic diseases KW - W3 33190:Therapy: Other KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17380060?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Pharmaceutical+Design&rft.atitle=Parasitic+Infections.+Treatment+and+Developmental+Therapeutics.+1.+Necatoriasis&rft.au=Georgiev%2C+V+St&rft.aulast=Georgiev&rft.aufirst=V&rft.date=1999-07-01&rft.volume=5&rft.issue=7&rft.spage=545&rft.isbn=&rft.btitle=&rft.title=Current+Pharmaceutical+Design&rft.issn=13816128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Anti-Infective Agents. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Parasitic diseases ER - TY - JOUR T1 - Chlamydial Colonization of Multiple Mucosae following Infection by Any Mucosal Route AN - 17373078; 4572028 AB - Chlamydia trachomatis inoculated by any mucosal route colonized multiple murine mucosae and, in most cases, the spleen, liver, and kidneys. Cell-to-cell transmission, systemic dissemination, and autoinoculation of infectious fluids may have contributed to chlamydial spread. Intermucosal trafficking of protective T cells cannot be accurately evaluated by using live chlamydial challenges. JF - Infection and Immunity AU - Perry, L L AU - Hughes, S AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 3686 EP - 3689 VL - 67 IS - 7 SN - 0019-9567, 0019-9567 KW - mice KW - Microbiology Abstracts B: Bacteriology KW - Colonization KW - Mucosa KW - Kidney KW - Liver KW - Spleen KW - Chlamydia trachomatis KW - J 02855:Human Bacteriology: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17373078?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Chlamydial+Colonization+of+Multiple+Mucosae+following+Infection+by+Any+Mucosal+Route&rft.au=Perry%2C+L+L%3BHughes%2C+S&rft.aulast=Perry&rft.aufirst=L&rft.date=1999-07-01&rft.volume=67&rft.issue=7&rft.spage=3686&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Spleen; Liver; Kidney; Colonization; Mucosa ER - TY - JOUR T1 - Alcohol, slow wave sleep, and the somatotropic axis AN - 17332169; 4598297 AB - When alcohol is a large proportion of daily nutrient energy, the network of signals for energy homeostasis appears to adapt with abnormal patterns of sleep and growth hormone (GH) release along with gradual acquisition of an addictive physical dependency on alcohol. Early relapse during treatment of alcoholism is associated with a lower GH response to challenge, perhaps reflecting an altered balance of somatostatin (SS) to somatotropin releasing hormone (GHRH) that also affects slow wave sleep (SWS) in dependent patients. Normal patterns of sleep have progressively shorter SWS episodes and longer rapid eye movement (REM) episodes during the overall sleep period, but the early sleep cycles of alcoholics have truncated or non-existent SWS episodes, and the longer REM episodes occur in early cycles. During SWS delta wave activity, the hypothalamus releases GHRH, which causes the pituitary to release GH. Alcohol-dependent patients have lower levels of SWS power and GH release than normal subjects, and efforts to understand the molecular basis for this maladaptation and its relation to continued alcohol dependence merit encouragement. More needs to be learned about the possibility of decreasing alcohol dependency by increasing SWS or enhancing GHRH action. JF - Alcohol AU - Lands, WEM AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Willco Building, Suite 400, 6000 Executive Boulevard, Bethesda, MD 20892-7003, USA, wlands@willco.niaaa.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 109 EP - 122 VL - 18 IS - 2-3 SN - 0741-8329, 0741-8329 KW - man KW - somatotropin-releasing hormone KW - Toxicology Abstracts KW - Growth hormone KW - Sleep KW - Endocrine system KW - Somatostatin KW - Ethanol KW - Growth hormone-releasing hormone KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17332169?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol&rft.atitle=Alcohol%2C+slow+wave+sleep%2C+and+the+somatotropic+axis&rft.au=Lands%2C+WEM&rft.aulast=Lands&rft.aufirst=WEM&rft.date=1999-07-01&rft.volume=18&rft.issue=2-3&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Alcohol&rft.issn=07418329&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Growth hormone-releasing hormone; Somatostatin; Growth hormone; Endocrine system; Ethanol; Sleep ER - TY - JOUR T1 - Diesel Exhaust Exposure Among Adolescents in Harlem: A Community-Driven Study AN - 17311696; 4590574 AB - Objectives. This study sought individual-level data on diesel exhaust exposure and lung function among adolescents in Harlem as part of a community-driven research agenda. Methods. High school students administered in-person surveys to seventh grade students to ascertain information on demographics, asthma history, and self-reported and maternal smoking. Urine samples were assayed for 1-hydroxypyrene (1-HP), a marker of diesel exhaust exposure, and cotinine, a marker of tobacco smoke exposure. Computer-assisted spirometry was used to measure lung function. Results. Three quarters (76%) of the participating students had detectable levels of 1-HP. Three students (13%) had an FEF sub(25-75) of less than or equal to 80% of their predicted measurements, and 4 students (17%) had results between 80% and 90% of the predicted value, all of which are suggestive of possible lung impairment. Conclusions. These data suggest that most adolescents in Harlem are exposed to detectable levels of diesel exhaust, a known exacerbator and possible cause of chronic lung disorders such as asthma. Community-driven research initiatives are important for empowering communities to make needed changes to improve their environments and health. JF - American Journal of Public Health AU - Northridge, ME AU - Yankura, J AU - Kinney, P L AU - Santella, R M AU - Shepard, P AU - Riojas, Y AU - Aggarwal, M AU - Strickland, P AD - NIEHS Center for Environmental Health in Northern Manhattan 60 Haven Ave, Level B-1, New York, NY 10032, USA, men11@columbia.edu Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 998 EP - 1002 VL - 89 IS - 7 SN - 0090-0036, 0090-0036 KW - USA, New York, New York KW - USA, New York, New York City KW - diesel KW - man KW - respiratory tract diseases KW - Toxicology Abstracts; Health & Safety Science Abstracts; Pollution Abstracts KW - Public health KW - Lung diseases KW - Asthma KW - Diesel engines KW - Combustion products KW - Pollution effects KW - Adolescents KW - Urban areas KW - Polycyclic aromatic hydrocarbons KW - Adolescence KW - Air pollution KW - Automotive exhaust emissions KW - X 24190:Polycyclic hydrocarbons KW - H 11000:Diseases/Injuries/Trauma KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17311696?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Public+Health&rft.atitle=Diesel+Exhaust+Exposure+Among+Adolescents+in+Harlem%3A+A+Community-Driven+Study&rft.au=Northridge%2C+ME%3BYankura%2C+J%3BKinney%2C+P+L%3BSantella%2C+R+M%3BShepard%2C+P%3BRiojas%2C+Y%3BAggarwal%2C+M%3BStrickland%2C+P&rft.aulast=Northridge&rft.aufirst=ME&rft.date=1999-07-01&rft.volume=89&rft.issue=7&rft.spage=998&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Public+Health&rft.issn=00900036&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pollution effects; Urban areas; Combustion products; Adolescents; Asthma; Automotive exhaust emissions; Air pollution; Public health; Diesel engines; Polycyclic aromatic hydrocarbons; Lung diseases; Adolescence ER - TY - JOUR T1 - Comparative Genomics of the Archaea (Euryarchaeota): Evolution of Conserved Protein Families, the Stable Core, and the Variable Shell AN - 17307016; 4584284 AB - Comparative analysis of the protein sequences encoded in the four euryarchaeal species whose genomes have been sequenced completely (Methanococcus jannaschii, Methanobacterium thermoautotrophicum, Archaeoglobus fulgidus, and Pyrococcus horikoshii) revealed 1326 orthologous sets, of which 543 are represented in all four species. The proteins that belong to these conserved euryarchaeal families comprise 31%-35% of the gene complement and may be considered the evolutionarily stable core of the archaeal genomes. The core gene set includes the great majority of genes coding for proteins involved in genome replication and expression, but only a relatively small subset of metabolic functions. For many gene families that are conserved in all euryarchaea, previously undetected orthologs in bacteria and eukaryotes were identified. A number of euryarchaeal synapomorphies (unique shared characters) were identified; these are protein families that possess sequence signatures or domain architectures that are conserved in all euryarchaea but are not found in bacteria or eukaryotes. In addition, euryarchaea-specific expansions of several protein and domain families were detected. In terms of their apparent phylogenetic affinities, the archaeal protein families split into bacterial and eukaryotic families. The majority of the proteins that have only eukaryotic orthologs or show the greatest similarity to their eukaryotic counterparts belong to the core set. The families of euryarchaeal genes that are conserved in only two or three species constitute a relatively mobile component of the genomes whose evolution should have involved multiple events of lineage-specific gene loss and horizontal gene transfer. Frequently these proteins have detectable orthologs only in bacteria or show the greatest similarity to the bacterial homologs, which might suggest a significant role of horizontal gene transfer from bacteria in the evolution of the euryarchaeota. JF - Genome Research AU - Makarova, K S AU - Aravind, L AU - Galperin, MY AU - Grishin, N V AU - Tatusov, R L AU - Wolf, YI AU - Koonin, E V AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA, koonin@ncbi.nlm.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 608 EP - 628 VL - 9 IS - 7 SN - 1054-9803, 1054-9803 KW - euryarchaeota KW - evolution KW - nucleotide sequence KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Phylogeny KW - Genetic analysis KW - Archaeoglobus fulgidus KW - Pyrococcus horikoshii KW - Methanococcus jannaschii KW - Methanobacterium thermoautotrophicum KW - Genetic relationship KW - J 02710:Identification, taxonomy and typing KW - G 07260:Taxonomy, systematics and evolutionary genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17307016?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genome+Research&rft.atitle=Comparative+Genomics+of+the+Archaea+%28Euryarchaeota%29%3A+Evolution+of+Conserved+Protein+Families%2C+the+Stable+Core%2C+and+the+Variable+Shell&rft.au=Makarova%2C+K+S%3BAravind%2C+L%3BGalperin%2C+MY%3BGrishin%2C+N+V%3BTatusov%2C+R+L%3BWolf%2C+YI%3BKoonin%2C+E+V&rft.aulast=Makarova&rft.aufirst=K&rft.date=1999-07-01&rft.volume=9&rft.issue=7&rft.spage=608&rft.isbn=&rft.btitle=&rft.title=Genome+Research&rft.issn=10549803&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaeoglobus fulgidus; Methanobacterium thermoautotrophicum; Methanococcus jannaschii; Pyrococcus horikoshii; Genetic relationship; Phylogeny; Genetic analysis ER - TY - JOUR T1 - Antitumor Immunization with a Minimal Peptide Epitope (G9-209-2M) Leads to a Functionally Heterogeneous CTL Response AN - 17305403; 4580278 AB - The goal of experimental clinical protocols using peptide antigen for active vaccination and treatment of patients with metastatic cancer is to induce a vigorous cytotoxic T lymphocyte (CTL) response against the immunizing antigen, and thereby against tumor cells expressing the antigen. However, the magnitude and breadth of human CTL responses induced by peptide immunization, and in particular against antigens expressed by normal tissues as well as tumors, is not well characterized. This issue was examined by characterizing CTL cloids derived from peripheral blood mononuclear cells of three patients who received peptide immunization as treatment for metastatic melanoma. All patients received G9-209-2M peptide, a modified epitope of the gp100 melanoma-associated antigen, The results indicated that the CTL response induced by this peptide antigen was highly heterogeneous both in terms of avidity toward the peptide antigen and recognition of tumor cell lines. Furthermore, avidity of each CTL cloid for the native peptide was highly predictive of tumor reactivity. These results ate discussed in terms of their implications for peptide vaccination and adoptive tumor immunotherapy. JF - Journal of Immunotherapy with Emphasis on Tumor Biology AU - Dudley, ME AU - Nishimura, MI AU - Holt, AKC AU - Rosenberg, SA AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 288 EP - 298 VL - 22 IS - 4 SN - 1053-8550, 1053-8550 KW - cancer vaccines KW - immunology KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Adoptive immunotherapy KW - Lymphocytes T KW - Tumors KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17305403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.atitle=Antitumor+Immunization+with+a+Minimal+Peptide+Epitope+%28G9-209-2M%29+Leads+to+a+Functionally+Heterogeneous+CTL+Response&rft.au=Dudley%2C+ME%3BNishimura%2C+MI%3BHolt%2C+AKC%3BRosenberg%2C+SA&rft.aulast=Dudley&rft.aufirst=ME&rft.date=1999-07-01&rft.volume=22&rft.issue=4&rft.spage=288&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunotherapy+with+Emphasis+on+Tumor+Biology&rft.issn=10538550&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Adoptive immunotherapy; Tumors; Lymphocytes T ER - TY - JOUR T1 - New studies on trans-anethole oxide and trans-asarone oxide AN - 17304977; 4572603 AB - The widespread use of naturally occurring alkenylbenzenes as flavoring and fragrance agents has led to a long-standing interest in their toxicity and carcinogenicity. Among them several allyl- and propenylbenzenes have been found to be mutagenic and carcinogenic. It has been shown that the carcinogenicity of several allylbenzenes can be related to the formation of electrophilic sulfuric acid esters following 1 theta -hydroxylation. Unlike the allylbenzenes, the mechanisms of carcinogenesis of propenylbenzenes such as anethole and asarone are not clear. It has been reported that one of the main metabolic pathways of trans-anethole is the epoxidation of the side chain 1,2-double bond, which was responsible for cytotoxicity but not for genotoxicity. However, we report here that synthetic trans-anethole oxide prepared from trans-anethole and dimethyldioxirane is not only mutagenic for Salmonella tester strains but is also carcinogenic in the induction of hepatomas in B6C3F1 mice and skin papillomas in CD-1 mice. Synthetic trans-asarone oxide was also carcinogenic in the induction of hepatomas as well as mutagenic for Salmonella strains. Further studies are needed on these side chain oxides of trans-anethole and trans-asarone as possible metabolites in the toxicity, mutagenicity and carcinogenicity of these and other propenylbenzenes. JF - Carcinogenesis AU - Kim, S G AU - Liem, A AU - Stewart, B C AU - Miller, JA AD - Molecular Recognition Section, LBC, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA, seongk@intra.niddk.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 1303 EP - 1307 VL - 20 IS - 7 SN - 0143-3334, 0143-3334 KW - anethole KW - asarones KW - Toxicology Abstracts KW - Mutagenicity KW - Carcinogenicity KW - Flavorings KW - Structure-activity relationships KW - Fragrances KW - X 24140:Cosmetics, toiletries & household products KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17304977?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=New+studies+on+trans-anethole+oxide+and+trans-asarone+oxide&rft.au=Kim%2C+S+G%3BLiem%2C+A%3BStewart%2C+B+C%3BMiller%2C+JA&rft.aulast=Kim&rft.aufirst=S&rft.date=1999-07-01&rft.volume=20&rft.issue=7&rft.spage=1303&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenicity; Fragrances; Structure-activity relationships; Flavorings; Mutagenicity ER - TY - JOUR T1 - Effects of Environmental pH on Membrane Proteins in Borrelia burgdorferi AN - 17303041; 4571902 AB - Borrelia burgdorferi, the causative agent of Lyme disease, alternates between the microenvironments of the tick vector, Ixodes scapularis, and a mammalian host. The environmental conditions the spirochete encounters during its infectious cycle are suspected to differ greatly in many aspects, including available nutrients, temperature, and pH. Here we identify alterations in the membrane protein profile, as determined by immunoblotting and two-dimensional nonequilibrium pH gradient gel electrophoresis (2D-NEPHGE), that occur in virulent B. burgdorferi B31 as the pH of the medium is altered. Initial comparisons of cultures incubated at pHs 6.0, 7.0, and 8.0 yielded alterations in the expression of seven membrane proteins as determined by probing with hyperimmune rabbit serum. Six of these membrane proteins (54, 45, 44, 43, 35, and 24 kDa) were either present in increased amounts in or solely expressed by cultures incubated at pHs 6.0 and 7.0. The 24-kDa protein that decreased in expression at pH 8.0 was identified as outer surface protein C (OspC). In addition, a 42-kDa membrane protein increased in amount in cultures incubated at pH 8.0. Similar changes were observed with serum from a mouse infected by tick bite, with the recognition of two additional bands (48 and 46 kDa) unique to pHs 6.0 and 7.0. When membrane fractions were analyzed by 2D-NEPHGE, at least 37 changes in the membrane protein profile between cells incubated at pHs 6.0, 7.0, and 8.0 were observed by immunoblotting and silver staining. Environmental cues such as pH may prove important in the regulation of virulence determinants and factors necessary for the adaptation of B. burgdorferi to the tick or mammalian microcosm. JF - Infection and Immunity AU - Carroll, JA AU - Garon, C F AU - Schwan, T G AD - 903 South 4th St., Hamilton, MT 59840, USA, jcarroll@atlas.niaid.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 3181 EP - 3187 VL - 67 IS - 7 SN - 0019-9567, 0019-9567 KW - Borrelia burgdorferi KW - Ixodes scapularis KW - immunology KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Temperature effects KW - Membrane proteins KW - Gel electrophoresis KW - pH effects KW - J 02832:Antigenic properties and virulence KW - F 06008:Bacteria UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17303041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Effects+of+Environmental+pH+on+Membrane+Proteins+in+Borrelia+burgdorferi&rft.au=Carroll%2C+JA%3BGaron%2C+C+F%3BSchwan%2C+T+G&rft.aulast=Carroll&rft.aufirst=JA&rft.date=1999-07-01&rft.volume=67&rft.issue=7&rft.spage=3181&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Ixodes scapularis; pH effects; Temperature effects; Gel electrophoresis; Membrane proteins ER - TY - JOUR T1 - Is there a healthy worker effect for cancer incidence among women in Sweden? AN - 17293292; 4564702 AB - Our aim was to evaluate whether there is a healthy worker effect (HWE) for cancer incidence among women. HWE is a bias found in occupational studies that compare rates of disease among employed people to disease rates for the general population, which includes unemployed people (who may be less healthy than those who are employed). Data from the 1960 and 1970 Swedish censuses were used to identify all 1,659,940 Swedish women who were employed in either year. They were followed during 1971-1989 through linkages to the national cancer and death registers. Standardized incidence ratios (SIRs) were computed comparing employed women to the 1,627,873 women who were not employed in either 1960 or 1970. For the 545,857 women employed in both 1960 and 1970, the SIR for all cancers combined was 1.05 (1.04-1.06). When specific cancer sites were analyzed separately, the highest cancer risks were for cancers of the lung and bladder (SIR = 1.2) and reproductive organs (breast, ovary, endometrium, and cervix SIR = 1.1). Overall cancer risks were highest among full-time workers, younger workers, urban workers, and workers with the highest socioeconomic status (based on the woman's job title). These results show no general HWE for cancer incidence among employed Swedish women. JF - American Journal of Industrial Medicine AU - Gridley, G AU - Nyren, O AU - Dosemeci, M AU - Moradi, T AU - Adami, H-O AU - Carroll, L AU - Zahm, SH AD - NCI, EPS 8034-7244, Rockville, MD 20892-7244, USA, gridleyg@exchange.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 193 EP - 199 VL - 36 IS - 1 SN - 0271-3586, 0271-3586 KW - healthy worker effect KW - Health & Safety Science Abstracts KW - Risk assessment KW - Females KW - Cancer KW - Occupational exposure KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17293292?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Journal+of+Industrial+Medicine&rft.atitle=Is+there+a+healthy+worker+effect+for+cancer+incidence+among+women+in+Sweden%3F&rft.au=Gridley%2C+G%3BNyren%2C+O%3BDosemeci%2C+M%3BMoradi%2C+T%3BAdami%2C+H-O%3BCarroll%2C+L%3BZahm%2C+SH&rft.aulast=Gridley&rft.aufirst=G&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=193&rft.isbn=&rft.btitle=&rft.title=American+Journal+of+Industrial+Medicine&rft.issn=02713586&rft_id=info:doi/10.1002%2F%28SICI%291097-0274%28199907%2936%3A13.3.CO%3B2-D LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - SuppNotes - Special issue: Women's health: Occupation, cancer and reproduction. N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Occupational exposure; Cancer; Risk assessment; Females DO - http://dx.doi.org/10.1002/(SICI)1097-0274(199907)36:1<193::AID-AJIM27>3.3.CO;2-D ER - TY - JOUR T1 - Cancer therapy using a self-replicating RNA vaccine AN - 17280285; 4575208 AB - 'Naked' nucleic acid vaccines are potentially useful candidates for the treatment of patients with cancer, but their clinical efficacy has yet to be demonstrated. We sought to enhance the immunogenicity of a nucleic acid vaccine by making it 'self-replicating'. We accomplished this by using a gene encoding an RNA replicase polyprotein derived from the Semliki forest virus, in combination with a model antigen. A single intramuscular injection of a self-replicating RNA immunogen elicited antigen-specific antibody and CD8 super(+) T-cell responses at doses as low as 0.1 mu g. Pre-immunization with a self-replicating RNA vector protected mice from tumor challenge, and therapeutic immunization prolonged the survival of mice with established tumors. The self-replicating RNA vectors did not mediate the production of substantially more model antigen than a conventional DNA vaccine did in vitro. However, the enhanced efficacy in vivo correlated with a caspase-dependent apoptotic death in transfected cells. This death facilitated the uptake of apoptotic cells by dendritic cells, providing a potential mechanism for enhanced immunogenicity. Naked, non-infectious, self-replicating RNA may be an excellent candidate for the development of new cancer vaccines. JF - Nature Medicine AU - Ying, Han AU - Zaks, T Z AU - Wang, Rong-Fu AU - Irvine, K R AU - Kammula, U S AU - Marincola, F M AU - Leitner, W W AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, Building 10, Room 2B42, 10 Center Drive, Bethesda, MD 20892-1502, USA, restifo@nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 823 EP - 827 VL - 5 IS - 7 SN - 1078-8956, 1078-8956 KW - RNA vaccines KW - cancer vaccines KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Apoptosis KW - Tumors KW - Dendritic cells KW - Lymphocytes T KW - Vaccines KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews KW - N 14800:Immunological aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17280285?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Cancer+therapy+using+a+self-replicating+RNA+vaccine&rft.au=Ying%2C+Han%3BZaks%2C+T+Z%3BWang%2C+Rong-Fu%3BIrvine%2C+K+R%3BKammula%2C+U+S%3BMarincola%2C+F+M%3BLeitner%2C+W+W%3BRestifo%2C+N+P&rft.aulast=Ying&rft.aufirst=Han&rft.date=1999-07-01&rft.volume=5&rft.issue=7&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Apoptosis; Dendritic cells; Vaccines; Tumors; Lymphocytes T ER - TY - JOUR T1 - Oxazepam is mutagenic in vivo in Big Blue transgenic mice AN - 17270734; 4572587 AB - Although oxazepam (Serax registered ), a widely used benzodiazepine anxiolytic, does not induce gene mutations in vitro or chromosomal aberrations in vivo, it was found to be a hepatocarcinogen in a 2 year bioassay in B6C3F1 mice. Thus, it was of interest to determine whether this carcinogen is mutagenic in vivo. Male B6C3F1 Big Blue registered transgenic mice were fed 2500 p.p.m. oxazepam or control diet alone for 180 days and killed on the next day. The mutant frequency (MF) of lacI in control mice was 5.02 plus or minus 2.4x10 super(5), whereas the MF in the oxazepam-treated mice was 9.17 plus or minus 4.82x10 super(-5), a significant increase (P < 0.05). Correction of the mutant frequency of lacI from the oxazepam-treated mice for clonality resulted in a decrease in the mean mutant frequency to 8.15 plus or minus 2.54x10 super(-5). Although the mutant frequency difference was small, sequencing of a random collection of the mutants from each oxazepam-exposed mouse showed a significant difference (P < 0.015) in the mutation spectrum compared with that from control mice. In the oxazepam-exposed mice, an increase in G:C arrow right T:A and G:C arrow right C:G transversions and a concomitant decrease in G:C arrow right A:T transitions were observed. Clonal expansion of mutations at guanines in 5 theta -CpG-3 theta sequencing contexts at three sites was noted. It is postulated that some of the mutations found in the oxazepam-derived spectrum were due to oxidative damage elicited by induction of CYP2B isozymes as the result of chronic oxazepam administration. This study demonstrates that the in vivo Big Blue registered transgenic rodent mutation assay can detect mutations derived from a carcinogen that did not induce gene mutations in vitro or micronuclei in mouse bone marrow. Moreover, the sequencing of the recovered mutants can distinguish between the mutation spectrum from treated mice compared with that from control mice, thereby confirming the genotoxic consequences. JF - Carcinogenesis AU - Shane, B S AU - deBoer, J G AU - Glickman, B W AU - Cunningham, M L AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 1315 EP - 1321 VL - 20 IS - 7 SN - 0143-3334, 0143-3334 KW - oxazepam KW - Toxicology Abstracts KW - Anxiolytics KW - Mutagenicity KW - Benzodiazepine KW - Transgenic mice KW - X 24117:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17270734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Oxazepam+is+mutagenic+in+vivo+in+Big+Blue+transgenic+mice&rft.au=Shane%2C+B+S%3BdeBoer%2C+J+G%3BGlickman%2C+B+W%3BCunningham%2C+M+L&rft.aulast=Shane&rft.aufirst=B&rft.date=1999-07-01&rft.volume=20&rft.issue=7&rft.spage=1315&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Transgenic mice; Mutagenicity; Benzodiazepine; Anxiolytics ER - TY - JOUR T1 - Lysis and Lysis Inhibition in Bacteriophage T4: rV Mutations Reside in the Holin t Gene AN - 17270329; 4566096 AB - Upon infecting populations of susceptible host cells, T-even bacteriophages maximize their yield by switching from lysis at about 25 to 35 min at 37 degree C after infection by a single phage particle to long-delayed lysis (lysis inhibition) under conditions of sequential infection occurring when free phages outnumber host cells. The timing of lysis depends upon gene t and upon one or more rapid-lysis (r) genes whose inactivation prevents lysis inhibition. t encodes a holin that mediates the movement of the T4 endolysin though the inner cell membrane to its target, the cell wall. The rI protein has been proposed to sense superinfection. Of the five reasonably well characterized r genes, only two rI and rV, are clearly obligatory for lysis inhibition. We show here that rV mutations are alleles of t that probably render the t protein unable to respond to the lysis inhibition signal. The tr alleles cluster in the 5' third of t and produce a strong r phenotype, whereas conditional-lethal t alleles produce the classical t phenotype (inability to lyse) and other t alleles produce additional, still poorly understood phenotypes. tr mutations are dominant to t super(+), a result that suggests specific ways to probe T4 holin function. JF - Journal of Bacteriology AU - Dressman, H K AU - Drake, J W AD - Laboratory of Molecular Genetics E3-01, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709., drake@niehs.nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 4391 EP - 4396 VL - 181 IS - 14 SN - 0021-9193, 0021-9193 KW - double prime r gene KW - double prime rI gene KW - double prime rI protein KW - double prime rV gene KW - double prime t gene KW - double prime tr gene KW - endolysin KW - holin KW - r gene KW - rI gene KW - rI protein KW - rV gene KW - t gene KW - tr gene KW - Microbiology Abstracts B: Bacteriology; Virology & AIDS Abstracts; Genetics Abstracts KW - Lysis KW - Phage T4 KW - G 07312:Phages KW - J 02750:Phage-host interactions KW - V 22070:Phage-host interactions including lysogeny & transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17270329?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Lysis+and+Lysis+Inhibition+in+Bacteriophage+T4%3A+rV+Mutations+Reside+in+the+Holin+t+Gene&rft.au=Dressman%2C+H+K%3BDrake%2C+J+W&rft.aulast=Dressman&rft.aufirst=H&rft.date=1999-07-01&rft.volume=181&rft.issue=14&rft.spage=4391&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Phage T4; Lysis ER - TY - JOUR T1 - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) retards mammary gland involution in lactating Sprague-Dawley rats AN - 17268090; 4572586 AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a compound from cooked meat, is an established mammary gland carcinogen in female rats. Four doses of PhIP (150 mg/kg, p.o., once per day) were given to lactating Sprague-Dawley rats separated from their 10-day-old pups to initiate involution of the gland. Twenty-four hours after the last dose, apoptotic index in the mammary gland, as measured by the TUNEL assay, was significantly higher in the gland from control rats than in the PhIP-treated rats (4.757 plus or minus 1.066 versus 1.905 plus or minus 0.248%; P < 0.05). In comparison with controls, alveoli in the mammary gland of PhIP-treated rats were also visibly larger and contained more secretory epithelial cells. The expression of Bax, a stimulator of apoptosis, and Bcl-2, an inhibitor of apoptosis, were quantitated by western blotting. Accordingly, Bax expression was 2.7-fold higher in control rats, whereas Bcl-2 expression was 3.1-fold higher in PhIP-treated rats, both changes being statistically different (Student's t-test, P < 0.05). Immunohistochemistry further confirmed a lower expression of Bax and higher expression of Bcl-2 in secretory alveolar epithelial cells of the PhIP-treated mammary gland. The findings are consistent with the notion that exposure to PhIP retarded involution via partial inhibition of programmed cell death. To investigate possible mechanisms for the inhibitory effects of PhIP on mammary gland involution, serum levels of prolactin, an important hormone for the maintenance of lactation, were measured in virgin rats with regular estrous cycles given PhIP (150 mg/kg, p.o.) on the morning of diestrous. After one estrous cycle, on proestrous morning, serum prolactin levels were 1.3-fold higher after PhIP than after control vehicle (one-way ANOVA, Fisher LSD multiple comparison test, P < 0.05). PhIP exposure during involution was associated with the induction of benign mammary tumors. Seven out of 12 rats developed fibroadenomas, and one developed a tubulopapillary carcinoma within 1 year of receiving PhIP administration during involution (150 mg/kg, p.o., once per day for 5 days), and a high-fat diet (23.5% corn oil). An increase in serum prolactin level and the effects on mammary gland apoptosis seen with PhIP may have implications for the mechanisms of carcinogenic targeting of PhIP to the mammary gland. JF - Carcinogenesis AU - Venugopal, M AU - Callaway, A AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892-4255, USA, elizabeth_snyderwine@nih.gov Y1 - 1999/07// PY - 1999 DA - Jul 1999 SP - 1309 EP - 1314 VL - 20 IS - 7 SN - 0143-3334, 0143-3334 KW - 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine KW - rats KW - Toxicology Abstracts KW - Meat KW - Mammary gland KW - Food KW - Carcinogens KW - X 24120:Food, additives & contaminants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17268090?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=2-Amino-1-methyl-6-phenylimidazo%5B4%2C5-b%5Dpyridine+%28PhIP%29+retards+mammary+gland+involution+in+lactating+Sprague-Dawley+rats&rft.au=Venugopal%2C+M%3BCallaway%2C+A%3BSnyderwine%2C+E+G&rft.aulast=Venugopal&rft.aufirst=M&rft.date=1999-07-01&rft.volume=20&rft.issue=7&rft.spage=1309&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogens; Mammary gland; Food; Meat ER - TY - JOUR T1 - A Preliminary CD and NMR Study of the Escherichia coli DNA Polymerase III Theta Subunit AN - 17261297; 4554903 AB - The theta subunit of DNA polymerase III, the main replicative polymerase of Escherichia coli, has been examined by circular dichroism and by NMR spectroscopy. The polymerase core consists of three subunits: alpha , member of , and theta , with alpha possessing the polymerase activity, member of functioning as a proofreading exonuclease, and theta , a small subunit of 8.9 kD, of undetermined function. The theta subunit has been expressed in E. coli, and a CD analysis of theta indicates the presence of a significant amount of secondary structure: similar to 52% alpha helix, 9% beta sheet, 21% turns, and 18% random coil. However, at higher concentrations, theta yields a poorly-resolved 1D proton NMR spectrum in which both the amide protons and the methyl protons show poor chemical shift dispersion. Subsequent super(1)H- super(15)N HSQC analysis of uniformly- super(15)N-labeled theta supports the conclusion that approximately half of the protein is reasonably well-structured. Another quarter of the protein, probably including some of the N-terminal region, is highly mobile, exhibiting a chemical shift pattern indicative of random coil structure. The remaining amide resonances exhibit significant broadening, indicative of intermolecular and/or intramolecular exchange processes. Improved chemical shift dispersion and greater uniformity of resonance intensities in the super(1)H- super(15)N HSQC spectra resulted when [U- super(15)N]- theta was examined in the presence of member of 186-the N-terminal domain of the member of -subunit. Further work is currently in progress to define the solution structure of theta and the theta - member of 186 complex. JF - Proteins: Structure, Function & Genetics AU - Li, Dawei AU - Allen, D L AU - Harvey, S AU - Perrino, F W AU - Schaaper, R M AU - London, R E AD - Laboratory of Structural Biology, MR-01, NIEHS, Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1999/07/01/ PY - 1999 DA - 1999 Jul 01 SP - 111 EP - 116 VL - 36 IS - 1 SN - 0887-3585, 0887-3585 KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - DNA-directed DNA polymerase KW - C.D. KW - Escherichia coli KW - N.M.R. KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17261297?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proteins%3A+Structure%2C+Function+%26+Genetics&rft.atitle=A+Preliminary+CD+and+NMR+Study+of+the+Escherichia+coli+DNA+Polymerase+III+Theta+Subunit&rft.au=Li%2C+Dawei%3BAllen%2C+D+L%3BHarvey%2C+S%3BPerrino%2C+F+W%3BSchaaper%2C+R+M%3BLondon%2C+R+E&rft.aulast=Li&rft.aufirst=Dawei&rft.date=1999-07-01&rft.volume=36&rft.issue=1&rft.spage=111&rft.isbn=&rft.btitle=&rft.title=Proteins%3A+Structure%2C+Function+%26+Genetics&rft.issn=08873585&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; C.D.; N.M.R.; DNA-directed DNA polymerase ER - TY - JOUR T1 - Efficient Transfer of a Tumor Antigen-Reactive TCR to Human Peripheral Blood Lymphocytes Confers Anti-Tumor Reactivity AN - 17259734; 4558293 AB - The tumor-associated-Ag MART-1 is expressed by most human melanomas. The genes encoding an alpha beta TCR from a MART-1-specific, HLA-A2-restricted, human T cell clone have been efficiently transferred and expressed in human PBL. These retrovirally transduced PBL cultures were MART-1 peptide reactive, and most cultures recognized HLA-A2 super(+) melanoma lines. Limiting dilution clones were generated from three bulk transduced PBL cultures to investigate the function of individual clones within the transduced cultures. Twenty-nine of 29 CD8 super(+) clones specifically secreted IFN- gamma in response to T2 cells pulsed with MART-1 sub((27-35)) peptide, and 23 of 29 specifically secreted IFN- gamma in response to HLA-A2 super(+) melanoma lines. Additionally, 23 of 29 CD8 super(+) clones lysed T2 cells pulsed with the MART-1 sub((27-35)) peptide and 15 of 29 lysed the HLA-A2 super(+) melanoma line 888. CD4 super(+) clones specifically secreted IFN- gamma in response to T2 cells pulsed with the MART-1 sub((27-35)) peptide. TCR gene transfer to patient PBL can produce CTL with anti-tumor reactivity in vitro and could potentially offer a treatment for patients with metastatic melanoma. This approach could also be applied to the treatment of other tumors and viral infections. Additionally, TCR gene transfer offers unique opportunities to study the fate of adoptively transferred T cells in vivo. JF - Journal of Immunology AU - Clay, T M AU - Custer, M C AU - Sachs, J AU - Hwu, P AU - Rosenberg, SA AU - Nishimura, MI AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B06, 9000 Rockville Pike, Bethesda, MD 20892, USA, nishimur@helix.nih.gov Y1 - 1999/07/01/ PY - 1999 DA - 1999 Jul 01 SP - 507 EP - 513 VL - 163 IS - 1 SN - 0022-1767, 0022-1767 KW - MART-1 antigen KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Melanoma KW - Gene transfer KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Adoptive transfer KW - F 06818:Cancer immunotherapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17259734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Efficient+Transfer+of+a+Tumor+Antigen-Reactive+TCR+to+Human+Peripheral+Blood+Lymphocytes+Confers+Anti-Tumor+Reactivity&rft.au=Clay%2C+T+M%3BCuster%2C+M+C%3BSachs%2C+J%3BHwu%2C+P%3BRosenberg%2C+SA%3BNishimura%2C+MI&rft.aulast=Clay&rft.aufirst=T&rft.date=1999-07-01&rft.volume=163&rft.issue=1&rft.spage=507&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Gene transfer; Antigen (tumor-associated); Adoptive transfer; Lymphocytes T ER - TY - JOUR T1 - Murine TIMP-2 gene-targeted mutation. AN - 69905601; 10415763 JF - Annals of the New York Academy of Sciences AU - Caterina, J AU - Caterina, N AU - Yamada, S AU - Holmbäck, K AU - Longenecker, G AU - Shi, J AU - Netzel-Arnett, S AU - Engler, J AU - Yermovski, A AU - Windsor, J AU - Birkedal-Hansen, H AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. jc239h@nih.gov Y1 - 1999/06/30/ PY - 1999 DA - 1999 Jun 30 SP - 528 EP - 530 VL - 878 SN - 0077-8923, 0077-8923 KW - Concanavalin A KW - 11028-71-0 KW - Tissue Inhibitor of Metalloproteinase-2 KW - 127497-59-0 KW - Gelatinases KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Index Medicus KW - Animals KW - Chromosome Deletion KW - Enzyme Activation KW - Mice KW - Fibroblasts -- metabolism KW - Mutagenesis KW - Mice, Knockout KW - Base Sequence KW - Cells, Cultured KW - Recombination, Genetic KW - Molecular Sequence Data KW - Gelatinases -- metabolism KW - Metalloendopeptidases -- metabolism KW - Concanavalin A -- pharmacology KW - Tissue Inhibitor of Metalloproteinase-2 -- deficiency KW - Tissue Inhibitor of Metalloproteinase-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69905601?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Murine+TIMP-2+gene-targeted+mutation.&rft.au=Caterina%2C+J%3BCaterina%2C+N%3BYamada%2C+S%3BHolmb%C3%A4ck%2C+K%3BLongenecker%2C+G%3BShi%2C+J%3BNetzel-Arnett%2C+S%3BEngler%2C+J%3BYermovski%2C+A%3BWindsor%2C+J%3BBirkedal-Hansen%2C+H&rft.aulast=Caterina&rft.aufirst=J&rft.date=1999-06-30&rft.volume=878&rft.issue=&rft.spage=528&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-11 N1 - Date created - 1999-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The effects of sustained elevated levels of circulating tissue inhibitor of metalloproteinases-1 on the development of breast cancer in mice. AN - 69902759; 10415821 JF - Annals of the New York Academy of Sciences AU - Buck, T B AU - Yoshiji, H AU - Harris, S R AU - Bunce, O R AU - Thorgeirsson, U P AD - Tumor Biology and Carcinogenesis Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06/30/ PY - 1999 DA - 1999 Jun 30 SP - 732 EP - 735 VL - 878 SN - 0077-8923, 0077-8923 KW - Tissue Inhibitor of Metalloproteinase-1 KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Medroxyprogesterone Acetate KW - C2QI4IOI2G KW - Gelatinases KW - EC 3.4.24.- KW - Metalloendopeptidases KW - Matrix Metalloproteinase 2 KW - EC 3.4.24.24 KW - Index Medicus KW - Animals KW - Humans KW - Gelatinases -- antagonists & inhibitors KW - Enzyme-Linked Immunosorbent Assay KW - Mice KW - Metalloendopeptidases -- antagonists & inhibitors KW - Mice, Transgenic KW - Aging -- blood KW - Female KW - Mammary Neoplasms, Experimental -- chemically induced KW - Tissue Inhibitor of Metalloproteinase-1 -- blood KW - Mammary Neoplasms, Experimental -- prevention & control KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics KW - Mammary Neoplasms, Experimental -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69902759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=The+effects+of+sustained+elevated+levels+of+circulating+tissue+inhibitor+of+metalloproteinases-1+on+the+development+of+breast+cancer+in+mice.&rft.au=Buck%2C+T+B%3BYoshiji%2C+H%3BHarris%2C+S+R%3BBunce%2C+O+R%3BThorgeirsson%2C+U+P&rft.aulast=Buck&rft.aufirst=T&rft.date=1999-06-30&rft.volume=878&rft.issue=&rft.spage=732&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-11 N1 - Date created - 1999-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Redox signaling: hydrogen peroxide as intracellular messenger. AN - 69898552; 10410302 AB - Although superoxide anions (O2.-) and H2O2 are generally considered to be toxic by-products of respiration, recent evidence suggests that the production of these reactive oxygen species (ROS) might be an integral component of membrane receptor signaling. In mammalian cells, a variety of extracellular stimuli have recently been shown to induce a transient increase in the intracellular concentration of ROS, and specific inhibition of the ROS generation resulted in a complete blockage of stimulant-dependent signaling. In the next few years, therefore, a flurry of research activity is expected in relation to the elucidation of ROS production in response to receptor stimulation, identification of ROS target molecules, and investigation of ROS elimination. The goal of this report is to review our current knowledge of ROS-regulated signal transduction and propose future directions. JF - Experimental & molecular medicine AU - Rhee, S G AD - Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. sgrhee@nih.gov Y1 - 1999/06/30/ PY - 1999 DA - 1999 Jun 30 SP - 53 EP - 59 VL - 31 IS - 2 SN - 1226-3613, 1226-3613 KW - Reactive Oxygen Species KW - 0 KW - Hydrogen Peroxide KW - BBX060AN9V KW - Index Medicus KW - Prokaryotic Cells -- metabolism KW - Oxidation-Reduction KW - Eukaryotic Cells -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Humans KW - Hydrogen Peroxide -- metabolism KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69898552?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+%26+molecular+medicine&rft.atitle=Redox+signaling%3A+hydrogen+peroxide+as+intracellular+messenger.&rft.au=Rhee%2C+S+G&rft.aulast=Rhee&rft.aufirst=S&rft.date=1999-06-30&rft.volume=31&rft.issue=2&rft.spage=53&rft.isbn=&rft.btitle=&rft.title=Experimental+%26+molecular+medicine&rft.issn=12263613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-17 N1 - Date created - 1999-09-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Androgen receptor mutation in Kennedy's disease. AN - 69932610; 10434308 AB - Kennedy's disease is an X-linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen receptor, the predominant effect of expansion is probably a toxic gain of function, similar to the mechanism of other polyglutamine expansion diseases. Features of the neurodegenerative phenotype of Kennedy's disease have now been reproduced in transgenic animals and neuronal cell culture. Nuclear inclusions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy's disease. JF - Philosophical transactions of the Royal Society of London. Series B, Biological sciences AU - Fischbeck, K H AU - Lieberman, A AU - Bailey, C K AU - Abel, A AU - Merry, D E AD - Neurogenetics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/06/29/ PY - 1999 DA - 1999 Jun 29 SP - 1075 EP - 1078 VL - 354 IS - 1386 SN - 0962-8436, 0962-8436 KW - Peptides KW - 0 KW - Receptors, Androgen KW - polyglutamine KW - 26700-71-0 KW - Index Medicus KW - United States KW - Animals KW - X Chromosome KW - Humans KW - Transcription, Genetic KW - Mice KW - Peptides -- genetics KW - Mice, Transgenic KW - Trinucleotide Repeat Expansion -- genetics KW - Motor Neuron Disease -- genetics KW - Muscular Atrophy, Spinal -- genetics KW - Receptors, Androgen -- genetics KW - Mutation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69932610?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.atitle=Androgen+receptor+mutation+in+Kennedy%27s+disease.&rft.au=Fischbeck%2C+K+H%3BLieberman%2C+A%3BBailey%2C+C+K%3BAbel%2C+A%3BMerry%2C+D+E&rft.aulast=Fischbeck&rft.aufirst=K&rft.date=1999-06-29&rft.volume=354&rft.issue=1386&rft.spage=1075&rft.isbn=&rft.btitle=&rft.title=Philosophical+transactions+of+the+Royal+Society+of+London.+Series+B%2C+Biological+sciences&rft.issn=09628436&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-26 N1 - Date created - 1999-08-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1991 Jul 4;352(6330):77-9 [2062380] J Neurochem. 1999 Jan;72(1):185-95 [9886069] Mol Endocrinol. 1996 Dec;10(12):1527-35 [8961263] Neurology. 1968 Jul;18(7):671-80 [4233749] Science. 1977 Jul 1;197(4298):77-9 [867053] Brain. 1989 Feb;112 ( Pt 1):209-32 [2917278] J Neurosci. 1989 Nov;9(11):3908-14 [2585059] Nat Genet. 1992 Dec;2(4):301-4 [1303283] Nat Genet. 1993 Oct;5(2):184-8 [8252045] Nat Genet. 1995 Feb;9(2):191-6 [7719348] Nat Genet. 1996 Jun;13(2):196-202 [8640226] Neurobiol Dis. 1997;3(4):313-23 [9173928] Cell. 1997 Aug 8;90(3):537-48 [9267033] Neuron. 1997 Aug;19(2):333-44 [9292723] Science. 1997 Sep 26;277(5334):1990-3 [9302293] J Neurochem. 1998 Mar;70(3):1054-60 [9489725] Hum Mol Genet. 1998 Apr;7(4):693-701 [9499423] Hum Mol Genet. 1998 Jun;7(6):959-67 [9580659] Cell. 1998 Jun 12;93(6):939-49 [9635424] Ann Neurol. 1998 Aug;44(2):249-54 [9708548] Am J Pathol. 1998 Sep;153(3):695-701 [9736019] Biochem Biophys Res Commun. 1998 Nov 9;252(1):145-50 [9813160] Cell. 1996 Nov 1;87(3):493-506 [8898202] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of Rho and ADP-ribosylation factor GTPases on phospholipase D activity in intact human adenocarcinoma A549 cells. AN - 69832308; 10373471 AB - Phospholipase D (PLD) has been implicated as a crucial signaling enzyme in secretory pathways. Two 20-kDa guanine nucleotide-binding proteins, Rho and ADP-ribosylation factor (ARF), are involved in the regulation of secretion and can activate PLD in vitro. We investigated in intact (human adenocarcinoma A549 cells) the role of RhoA and ARF in activation of PLD by phorbol 12-myristate 13-acetate, bradykinin, and/or sphingosine 1-phosphate. To express recombinant Clostridium botulinum C3 exoenzyme (using double subgenomic recombinant Sindbis virus C3), an ADP-ribosyltransferase that inactivates Rho, or dominant-negative Rho containing asparagine at position 19 (using double subgenomic recombinant Sindbis virus Rho19N), cells were infected with Sindbis virus, a novel vector that allows rapid, high level expression of heterologous proteins. Expression of C3 toxin or Rho19N increased basal and decreased phorbol 12-myristate 13-acetate-stimulated PLD activity. Bradykinin or sphingosine 1-phosphate increased PLD activity with additive effects that were abolished in cells expressing C3 exoenzyme or Rho19N. In cells expressing C3, modification of Rho appeared to be incomplete, suggesting the existence of pools that differed in their accessibility to the enzyme. Similar results were obtained with cells scrape-loaded in the presence of C3; however, results with virus infection were more reproducible. To assess the role of ARF, cells were incubated with brefeldin A (BFA), a fungal metabolite that disrupts Golgi structure and inhibits enzymes that catalyze ARF activation by accelerating guanine nucleotide exchange. BFA disrupted Golgi structure, but did not affect basal or agonist-stimulated PLD activity, i.e. it did not alter a rate-limiting step in PLD activation. It also had no effect on Rho-stimulated PLD activity, indicating that RhoA action did not involve a BFA-sensitive pathway. A novel PLD activation mechanism, not sensitive to BFA and involving RhoA, was identified in human airway epithelial cells by use of a viral infection technique that preserves cell responsiveness. JF - The Journal of biological chemistry AU - Meacci, E AU - Vasta, V AU - Moorman, J P AU - Bobak, D A AU - Bruni, P AU - Moss, J AU - Vaughan, M AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06/25/ PY - 1999 DA - 1999 Jun 25 SP - 18605 EP - 18612 VL - 274 IS - 26 SN - 0021-9258, 0021-9258 KW - GTPase-Activating Proteins KW - 0 KW - Lysophospholipids KW - rho GTPase-activating protein KW - Brefeldin A KW - 20350-15-6 KW - sphingosine 1-phosphate KW - 26993-30-6 KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - exoenzyme C3, Clostridium botulinum KW - Phospholipase D KW - EC 3.1.4.4 KW - Botulinum Toxins KW - EC 3.4.24.69 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - rhoA GTP-Binding Protein KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Sphingosine KW - NGZ37HRE42 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Bradykinin KW - S8TIM42R2W KW - Index Medicus KW - Tumor Cells, Cultured KW - Humans KW - ADP Ribose Transferases -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Sphingosine -- pharmacology KW - Bradykinin -- pharmacology KW - Brefeldin A -- pharmacology KW - Golgi Apparatus -- metabolism KW - Sphingosine -- analogs & derivatives KW - Adenocarcinoma -- enzymology KW - Phospholipase D -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Adenylyl Cyclases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69832308?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Effect+of+Rho+and+ADP-ribosylation+factor+GTPases+on+phospholipase+D+activity+in+intact+human+adenocarcinoma+A549+cells.&rft.au=Meacci%2C+E%3BVasta%2C+V%3BMoorman%2C+J+P%3BBobak%2C+D+A%3BBruni%2C+P%3BMoss%2C+J%3BVaughan%2C+M&rft.aulast=Meacci&rft.aufirst=E&rft.date=1999-06-25&rft.volume=274&rft.issue=26&rft.spage=18605&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-15 N1 - Date created - 1999-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel cytolysis assay using fluorescent labeling and quantitative fluorescent scanning technology. AN - 69889360; 10410969 AB - A novel cellular cytotoxicity assay using Calcein acetoxymethyl (Calcein-AM), a cytoplasmic fluorescent label, has been developed as an alternative to the standard 51Chromium (Cr)-release. Target cells were loaded with Calcein-AM and then co-incubated with effector cells. An additional reagent, FluoroQuench, is added to extinguish fluorescence of dying target cells and of the culture media. Assay plates are read on a quantitative fluorescent scanner for determination of viable target cells. Percent lysis is calculated as one minus the percent viable cells as compared to fluorescent-labeled targets-only wells. The assay was tested to demonstrate the lytic activity of cytotoxic T lymphocyte (CTL) cultures, lymphokine-activated killer (LAK), and natural killer (NK) cell line effectors against peptide-pulsed and melanoma targets. In addition to the acquisition of results comparable to the 51Cr-release assay, the Calcein assay reliably measures cell-mediated cytotoxicity with little variance among replicates. The fluorescent assay represents a simple and useful alternative to the use of radioactive materials and adds the additional benefit of digital images and analysis. JF - Journal of immunological methods AU - Roden, M M AU - Lee, K H AU - Panelli, M C AU - Marincola, F M AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/06/24/ PY - 1999 DA - 1999 Jun 24 SP - 29 EP - 41 VL - 226 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Fluoresceins KW - 0 KW - Fluorescent Dyes KW - Chromium KW - 0R0008Q3JB KW - calcein AM KW - 148504-34-1 KW - Index Medicus KW - Tumor Cells, Cultured KW - Reproducibility of Results KW - Humans KW - Killer Cells, Lymphokine-Activated -- immunology KW - T-Lymphocytes, Cytotoxic -- immunology KW - Killer Cells, Natural -- immunology KW - Cytotoxicity Tests, Immunologic -- methods KW - Microscopy, Fluorescence -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69889360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunological+methods&rft.atitle=A+novel+cytolysis+assay+using+fluorescent+labeling+and+quantitative+fluorescent+scanning+technology.&rft.au=Roden%2C+M+M%3BLee%2C+K+H%3BPanelli%2C+M+C%3BMarincola%2C+F+M&rft.aulast=Roden&rft.aufirst=M&rft.date=1999-06-24&rft.volume=226&rft.issue=1-2&rft.spage=29&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunological+methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-13 N1 - Date created - 1999-08-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove. AN - 69837597; 10377391 AB - Ecteinascidin 743 (Et743, National Service Center 648766) is a potent antitumor agent from the Caribbean tunicate Ecteinascidia turbinata. Although Et743 is presently in clinical trials for human cancers, the mechanisms of antitumor activity of Et743 have not been elucidated. Et743 can alkylate selectively guanine N2 from the DNA minor groove, and this alkylation is reversed by DNA denaturation. Thus, Et743 differs from other DNA alkylating agents presently in the clinic (by both its biochemical activities and its profile of antitumor activity in preclinical models). In this study, we investigated cellular proteins that can bind to DNA alkylated by Et743. By using an oligonucleotide containing high-affinity Et743 binding sites and nuclear extracts from human leukemia CEM cells, we purified a 100-kDa protein as a cellular target of Et743 and identified it as topoisomerase I (top1). Purified top1 was then tested and found to produce cleavage complexes in the presence of Et743, whereas topoisomerase II had no effect. DNA alkylation was essential for the formation of top1-mediated cleavage complexes by Et743, and the distribution of the drug-induced top1 sites was different for Et743 and camptothecin. top1-DNA complexes were also detected in Et743-treated CEM cells by using cesium chloride gradient centrifugation followed by top1 immunoblotting. These data indicate that DNA minor groove alkylation by Et743 induces top1-mediated protein-linked DNA breaks and that top1 is a target for Et743 in vitro and in vivo. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Takebayashi, Y AU - Pourquier, P AU - Yoshida, A AU - Kohlhagen, G AU - Pommier, Y AD - Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/06/22/ PY - 1999 DA - 1999 Jun 22 SP - 7196 EP - 7201 VL - 96 IS - 13 SN - 0027-8424, 0027-8424 KW - Antineoplastic Agents, Alkylating KW - 0 KW - Dioxoles KW - Isoquinolines KW - Tetrahydroisoquinolines KW - DNA KW - 9007-49-2 KW - DNA Topoisomerases, Type I KW - EC 5.99.1.2 KW - trabectedin KW - ID0YZQ2TCP KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Urochordata KW - DNA -- chemistry KW - DNA -- drug effects KW - Alkylation KW - DNA Topoisomerases, Type I -- chemistry KW - Isoquinolines -- pharmacology KW - Isoquinolines -- chemistry KW - Antineoplastic Agents, Alkylating -- pharmacology KW - Dioxoles -- chemistry KW - DNA Topoisomerases, Type I -- pharmacology KW - Dioxoles -- pharmacology KW - Antineoplastic Agents, Alkylating -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69837597?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Poisoning+of+human+DNA+topoisomerase+I+by+ecteinascidin+743%2C+an+anticancer+drug+that+selectively+alkylates+DNA+in+the+minor+groove.&rft.au=Takebayashi%2C+Y%3BPourquier%2C+P%3BYoshida%2C+A%3BKohlhagen%2C+G%3BPommier%2C+Y&rft.aulast=Takebayashi&rft.aufirst=Y&rft.date=1999-06-22&rft.volume=96&rft.issue=13&rft.spage=7196&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-19 N1 - Date created - 1999-07-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Anal Biochem. 1975 May 12;65(1-2):125-31 [1130673] Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3496-501 [10097064] J Biol Chem. 1985 Nov 25;260(27):14873-8 [2997227] Biochemistry. 1986 Jan 14;25(1):9-16 [3006754] J Biol Chem. 1990 Jun 5;265(16):9418-22 [2160979] Mol Pharmacol. 1990 Jul;38(1):38-45 [2164630] Nucleic Acids Res. 1990 Nov 25;18(22):6611-9 [2174543] J Nat Prod. 1990 Jul-Aug;53(4):771-92 [2095373] J Biol Chem. 1991 Oct 25;266(30):20418-23 [1657924] Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11456-60 [1454834] J Biomol Struct Dyn. 1993 Apr;10(5):793-818 [8318161] Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8131-5 [7690143] Protein Expr Purif. 1994 Aug;5(4):364-70 [7950383] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11007-11 [7971998] Cancer Res. 1995 May 15;55(10):2097-103 [7743509] Biochemistry. 1995 May 30;34(21):7200-6 [7766631] Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8861-5 [7568032] J Med Chem. 1996 Feb 16;39(4):992-8 [8632422] Biochemistry. 1996 Oct 15;35(41):13303-9 [8873596] Mol Pharmacol. 1997 Jul;52(1):82-7 [9224816] Biochemistry. 1997 Oct 28;36(43):13285-91 [9341219] Cancer Res. 1997 Oct 15;57(20):4564-9 [9377570] Biochemistry. 1998 Mar 17;37(11):3818-23 [9521701] Mol Pharmacol. 1998 Jul;54(1):50-8 [9658189] Clin Cancer Res. 1998 Aug;4(8):1977-83 [9717828] Biochim Biophys Acta. 1998 Oct 1;1400(1-3):83-105 [9748515] Ann Oncol. 1998 Sep;9(9):981-7 [9818072] J Biol Chem. 1983 Oct 25;258(20):12728-32 [6313674] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: A phase I/II clinical trial AN - 17369008; 4555913 AB - To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with severe, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open- label, pilot study was performed. Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. All patients were able to tolerate the study medications without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2 receptor therapy may be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile. JF - Proceedings of the National Academy of Sciences, USA AU - Nussenblatt, R B AU - Fortin, E AU - Schiffman, R AU - Rizzo, L AU - Smith, J AU - Van Veldhuisen, P AU - Sran, P AU - Yaffe, A AU - Goldman, C K AU - Waldmann, T A AU - Whitcup, S M AD - Laboratory of Immunology, Clinical Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858 USA, DrBob@intra.nei.nih.gov Y1 - 1999/06/22/ PY - 1999 DA - 1999 Jun 22 SP - 7462 EP - 7466 VL - 96 IS - 13 SN - 0027-8424, 0027-8424 KW - man KW - cyclosporin A KW - interleukin 2 receptors KW - prednisone KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Uveitis KW - Monoclonal antibodies KW - Helper cells KW - Lymphocytes T KW - W3 33375:Antibodies KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17369008?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Treatment+of+noninfectious+intermediate+and+posterior+uveitis+with+the+humanized+anti-Tac+mAb%3A+A+phase+I%2FII+clinical+trial&rft.au=Nussenblatt%2C+R+B%3BFortin%2C+E%3BSchiffman%2C+R%3BRizzo%2C+L%3BSmith%2C+J%3BVan+Veldhuisen%2C+P%3BSran%2C+P%3BYaffe%2C+A%3BGoldman%2C+C+K%3BWaldmann%2C+T+A%3BWhitcup%2C+S+M&rft.aulast=Nussenblatt&rft.aufirst=R&rft.date=1999-06-22&rft.volume=96&rft.issue=13&rft.spage=7462&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/10.1073%2Fpnas.96.13.7462 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Monoclonal antibodies; Uveitis; Lymphocytes T; Helper cells DO - http://dx.doi.org/10.1073/pnas.96.13.7462 ER - TY - CONF T1 - Chromosomes 12 and 16 workshop. AN - 69826210; 10374740 AB - Recent linkage results independently derived from a large French Canadian pedigree and Danish kindreds coupled with supportive data from other studies provide compelling evidence for a bipolar disorder susceptibility locus on chromosome 12q23-q24. The idea is further strengthened by the finding that Darier's disease, which maps to this region, has been shown to cosegregate with affective disorder in a family. This linkage finding, however, was not supported in other independent genome scans. On chromosome 16, bipolar families from Denmark exhibited suggestive linkage with D16S510, on 16p13. Multipoint nonparametric analysis on the NIMH Genetics Initiative bipolar pedigrees yielded increased allele sharing that maximized approximately 18 cM proximal to the latter locus. In contrast, evidence of linkage was not detected in other panels of bipolar families that were presented. At 16p13, a maximum multipoint lod score of 4 for a latent class-derived phenotype that has aspects of alcohol dependence was found in a genome scan of 105 families from the Collaborative Study of the Genetics of Alcoholism, identifying a potential vulnerability locus. JF - American journal of medical genetics AU - Detera-Wadleigh, S D Y1 - 1999/06/18/ PY - 1999 DA - 1999 Jun 18 SP - 255 EP - 259 VL - 88 IS - 3 KW - Index Medicus KW - Humans KW - Genetic Predisposition to Disease KW - Schizophrenia -- genetics KW - Alcoholism -- genetics KW - Panic Disorder -- genetics KW - Genetic Linkage KW - Chromosomes, Human, Pair 16 KW - Bipolar Disorder -- genetics KW - Chromosomes, Human, Pair 12 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69826210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=American+journal+of+medical+genetics&rft.atitle=Chromosomes+12+and+16+workshop.&rft.au=Detera-Wadleigh%2C+S+D&rft.aulast=Detera-Wadleigh&rft.aufirst=S&rft.date=1999-06-18&rft.volume=88&rft.issue=3&rft.spage=255&rft.isbn=&rft.btitle=&rft.title=American+journal+of+medical+genetics&rft.issn=01487299&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-15 N1 - Date created - 1999-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eukaryotic Signalling Domain Homologues in Archaea and Bacteria. Ancient Ancestry and Horizontal Gene Transfer AN - 17259140; 4533843 AB - Phyletic distributions of eukaryotic signalling domains were studied using recently developed sensitive methods for protein sequence analysis, with an emphasis on the detection and accurate enumeration of homologues in bacteria and archaea. A major difference was found between the distributions of enzyme families that are typically found in all three divisions of cellular life and non-enzymatic domain families that are usually eukaryote-specific. Previously undetected bacterial homologues were identified for# plant pathogenesis-related proteins, Pad1, von Willebrand factor type A, src homology 3 and YWTD repeat-containing domains. Comparisons of the domain distributions in eukaryotes and prokaryotes enabled distinctions to be made between the domains originating prior to the last common ancestor of all known life forms and those apparently originating as consequences of horizontal gene transfer events. A number of transfers of signalling domains from eukaryotes to bacteria were confidently identified, in contrast to only a single case of apparent transfer from eukaryotes to archaea. JF - Journal of Molecular Biology AU - Ponting, C P AU - Aravind, L AU - Schultz, J AU - Bork, P AU - Koonin, E V AD - National Center for Biotechnology Information National Library of Medicine, National Institutes of Health, Bldg. 38A, Bethesda, 20894, MD, USA Y1 - 1999/06/18/ PY - 1999 DA - 1999 Jun 18 SP - 729 EP - 745 PB - Academic Press VL - 289 IS - 4 SN - 0022-2836, 0022-2836 KW - Bacteria KW - Pad1 protein KW - von Willebrand's factor KW - von willebrand factor KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Archaea KW - Gene transfer KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17259140?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Eukaryotic+Signalling+Domain+Homologues+in+Archaea+and+Bacteria.+Ancient+Ancestry+and+Horizontal+Gene+Transfer&rft.au=Ponting%2C+C+P%3BAravind%2C+L%3BSchultz%2C+J%3BBork%2C+P%3BKoonin%2C+E+V&rft.aulast=Ponting&rft.aufirst=C&rft.date=1999-06-18&rft.volume=289&rft.issue=4&rft.spage=729&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaea; Bacteria; Gene transfer ER - TY - JOUR T1 - The SIL gene is required for mouse embryonic axial development and left-right specification. AN - 69850833; 10385121 AB - The establishment of the main body axis and the determination of left-right asymmetry are fundamental aspects of vertebrate embryonic development. A link between these processes has been revealed by the frequent finding of midline defects in humans with left-right anomalies. This association is also seen in a number of mutations in mouse and zebrafish, and in experimentally manipulated Xenopus embryos. However, the severity of laterality defects accompanying abnormal midline development varies, and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos, which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left-right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2. JF - Nature AU - Izraeli, S AU - Lowe, L A AU - Bertness, V L AU - Good, D J AU - Dorward, D W AU - Kirsch, I R AU - Kuehn, M R AD - Genetics Department, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20889-5105, USA. Y1 - 1999/06/17/ PY - 1999 DA - 1999 Jun 17 SP - 691 EP - 694 VL - 399 IS - 6737 SN - 0028-0836, 0028-0836 KW - Hedgehog Proteins KW - 0 KW - Homeodomain Proteins KW - Intracellular Signaling Peptides and Proteins KW - LEFTY1 protein, human KW - Left-Right Determination Factors KW - NODAL protein, human KW - Nodal Protein KW - Nodal protein, mouse KW - Nuclear Proteins KW - Oncogene Proteins, Fusion KW - Paired Box Transcription Factors KW - Proteins KW - SHH protein, human KW - STIL protein, human KW - Trans-Activators KW - Transcription Factors KW - Transforming Growth Factor beta KW - homeobox protein PITX1 KW - homeobox protein PITX3 KW - homeobox protein PITX2 KW - 184787-43-7 KW - Index Medicus KW - Transforming Growth Factor beta -- biosynthesis KW - Animals KW - Homeodomain Proteins -- biosynthesis KW - Embryo, Mammalian -- abnormalities KW - Mice KW - Mice, Nude KW - Neural Tube Defects -- genetics KW - Transcription Factors -- biosynthesis KW - Mutagenesis KW - Heart -- embryology KW - Stem Cells KW - Gene Targeting KW - Signal Transduction KW - Body Patterning -- physiology KW - Embryonic and Fetal Development -- genetics KW - Embryonic and Fetal Development -- physiology KW - Proteins -- metabolism KW - Proteins -- genetics KW - Proteins -- physiology KW - Body Patterning -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69850833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature&rft.atitle=The+SIL+gene+is+required+for+mouse+embryonic+axial+development+and+left-right+specification.&rft.au=Izraeli%2C+S%3BLowe%2C+L+A%3BBertness%2C+V+L%3BGood%2C+D+J%3BDorward%2C+D+W%3BKirsch%2C+I+R%3BKuehn%2C+M+R&rft.aulast=Izraeli&rft.aufirst=S&rft.date=1999-06-17&rft.volume=399&rft.issue=6737&rft.spage=691&rft.isbn=&rft.btitle=&rft.title=Nature&rft.issn=00280836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-07 N1 - Date created - 1999-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses. AN - 69840663; 10380890 AB - The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response to 7-irradiation in the p53 wild-type ML-1 human myeloid cell line. Hybridization of the array to fluorescently-labeled RNA from treated and untreated cells was followed by computer analysis to derive relative changes in expression levels of the genes present in the array, which agreed well with actual quantitative changes in expression. Forty-eight sequences, 30 not previously identified as IR-responsive, were significantly regulated by IR. Induction by IR and other stresses of a subset of these genes, including the previously characterized CIP1/ WAF1, MDM2 and BAX genes, as well as nine genes not previously reported to be IR-responsive, was examined in a panel of 12 human cell lines. Responses varied widely in cell lines with different tissues of origin and different genetic backgrounds, highlighting the importance of cellular context to genotoxic stress responses. Two of the newly identified IR-responsive genes, FRA-1 and ATF3, showed a p53-associated component to their IR-induction, and this was confirmed both in isogenic human cell lines and in mouse thymus. The majority of the IR-responsive genes, however, showed no indication of p53-dependent regulation, representing a potentially important class of stress-responsive genes in leukemic cells. JF - Oncogene AU - Amundson, S A AU - Bittner, M AU - Chen, Y AU - Trent, J AU - Meltzer, P AU - Fornace, A J AD - National Institutes of Health, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/06/17/ PY - 1999 DA - 1999 Jun 17 SP - 3666 EP - 3672 VL - 18 IS - 24 SN - 0950-9232, 0950-9232 KW - DNA, Complementary KW - 0 KW - Fluorescent Dyes KW - RNA Probes KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - Methyl Methanesulfonate KW - AT5C31J09G KW - Index Medicus KW - Animals KW - Ultraviolet Rays KW - Tumor Suppressor Protein p53 -- physiology KW - Gamma Rays KW - Humans KW - Thymus Gland -- metabolism KW - RNA, Messenger -- analysis KW - Mice KW - Organ Specificity KW - RNA, Messenger -- genetics KW - Genes -- genetics KW - Methyl Methanesulfonate -- pharmacology KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Thymus Gland -- radiation effects KW - Tumor Suppressor Protein p53 -- genetics KW - Expressed Sequence Tags KW - Cell Line KW - RNA Probes -- genetics KW - Sequence Deletion KW - Gene Expression -- drug effects KW - DNA, Complementary -- genetics KW - Oligonucleotide Array Sequence Analysis KW - DNA Damage -- radiation effects KW - DNA Damage -- genetics KW - Gene Expression -- radiation effects KW - DNA Damage -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69840663?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Fluorescent+cDNA+microarray+hybridization+reveals+complexity+and+heterogeneity+of+cellular+genotoxic+stress+responses.&rft.au=Amundson%2C+S+A%3BBittner%2C+M%3BChen%2C+Y%3BTrent%2C+J%3BMeltzer%2C+P%3BFornace%2C+A+J&rft.aulast=Amundson&rft.aufirst=S&rft.date=1999-06-17&rft.volume=18&rft.issue=24&rft.spage=3666&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analyzing health surveys for cancer-related objectives. AN - 69843896; 10379963 AB - Large-scale health surveys conducted by government agencies record information on a large number of health-related variables. We review the use of these data for performing analyses that address cancer-related objectives. After describing the conduct of a large-scale health survey (the third National Health and Nutrition Examination Survey [NHANES III]), we discuss some of the issues involved in analyzing data collected in such a survey. In particular, the use of sample weights in the analysis and the importance of accounting for the complex survey design when estimating standard errors are discussed. Six applications are then presented that involve the following: 1) estimating demographic factors associated with snuff use, 2) estimating the association of type of health insurance with the probability of receiving a digital rectal examination, 3) estimating the association of body iron stores with the probability of later developing cancer, 4) estimating the changing rates of mammography screening in the United States between 1987 and 1992, 5) evaluating smoking and alcohol consumption as risk factors for digestive cancer by use of a population-based, case-control study, and 6) evaluating a randomized community-intervention experiment to encourage smoking cessation. These applications use data from the National Health Interview Survey, the NHANES I Epidemiologic Followup Study, the 1986 National Mortality Followback Survey, and the Community Intervention Trial for Smoking Cessation. The availability of public-use data files is discussed for surveys sponsored by the U.S. government that collect health-related information. We demonstrate that statistical methods and computer software are available for analyzing public-use data files of surveys to address different types of cancer-related objectives. JF - Journal of the National Cancer Institute AU - Graubard, B I AU - Korn, E L AD - Biostatistics Branch, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/06/16/ PY - 1999 DA - 1999 Jun 16 SP - 1005 EP - 1016 VL - 91 IS - 12 SN - 0027-8874, 0027-8874 KW - Iron KW - E1UOL152H7 KW - Index Medicus KW - Palpation KW - Rectum KW - Tobacco Use Disorder -- epidemiology KW - Humans KW - Digestive System Neoplasms -- etiology KW - Alcohol Drinking -- adverse effects KW - Smoking -- adverse effects KW - Prostatic Neoplasms -- prevention & control KW - Iron -- metabolism KW - Mammography -- statistics & numerical data KW - Risk Factors KW - Smoking Cessation KW - Insurance, Health KW - United States -- epidemiology KW - Male KW - Health Surveys KW - Data Interpretation, Statistical KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69843896?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Analyzing+health+surveys+for+cancer-related+objectives.&rft.au=Graubard%2C+B+I%3BKorn%2C+E+L&rft.aulast=Graubard&rft.aufirst=B&rft.date=1999-06-16&rft.volume=91&rft.issue=12&rft.spage=1005&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. AN - 69809985; 10359656 AB - Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor (AhR). In the present study we have examined the effect of the common dietary polyphenolic compounds quercetin and kaempferol on the transcription of CYP1A1 and the function of the AhR in MCF-7 human breast cancer cells. Quercetin caused a time- and concentration-dependent increase in the amount of CYP1A1 mRNA and CYP1A1 enzyme activity in MCF-7 cells. The increase in CYP1A1 mRNA caused by quercetin was prevented by the transcription inhibitor actinomycin D. Quercetin also caused an increase in the transcription of a chloramphenicol reporter vector containing the CYP1A1 promoter. Quercetin failed to induce CYP1A1 enzyme activity in AhR-deficient MCF-7 cells. Gel retardation studies demonstrated that quercetin activated the ability of the AhR to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the CYP1A1 promoter. These results indicate that quercetin's effect is mediated by the AhR. Kaempferol did not affect CYP1A1 expression by itself but it inhibited the transcription of CYP1A1 induced by the prototypical AhR ligand 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), as measured by a decrease in TCDD-induced CYP1A1 promoter-driven reporter vector activity, and CYP1A1 mRNA in cells. Kaempferol also abolished TCDD-induced XRE binding in a gel-shift assay. Both compounds were able to compete with TCDD for binding to a cytosolic extract of MCF-7 cells. Known ligands of the AhR are, for the most part, man-made compounds such as halogenated and polycyclic aromatic hydrocarbons. These results demonstrate that the dietary flavonols quercetin and kaempferol are natural, dietary ligands of the AhR that exert different effects on CYP1A1 transcription. JF - The Biochemical journal AU - Ciolino, H P AU - Daschner, P J AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Basic Research Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, MD 21702-1201, USA. hciolio@mail.ncifcrf.gov Y1 - 1999/06/15/ PY - 1999 DA - 1999 Jun 15 SP - 715 EP - 722 VL - 340 ( Pt 3) SN - 0264-6021, 0264-6021 KW - DNA Probes KW - 0 KW - Flavonoids KW - Flavonols KW - Kaempferols KW - Ligands KW - Polychlorinated Dibenzodioxins KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - Dactinomycin KW - 1CC1JFE158 KW - kaempferol KW - 731P2LE49E KW - Quercetin KW - 9IKM0I5T1E KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Index Medicus KW - Polychlorinated Dibenzodioxins -- antagonists & inhibitors KW - Cell Nucleus -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Cell Nucleus -- drug effects KW - RNA, Messenger -- genetics KW - Dactinomycin -- pharmacology KW - DNA Probes -- genetics KW - Tumor Cells, Cultured KW - RNA, Messenger -- metabolism KW - Polychlorinated Dibenzodioxins -- chemistry KW - Transfection KW - Binding, Competitive KW - Response Elements -- genetics KW - Promoter Regions, Genetic -- genetics KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - DNA Probes -- metabolism KW - Cytochrome P-450 CYP1A1 -- genetics KW - Transcription, Genetic -- drug effects KW - Quercetin -- antagonists & inhibitors KW - Quercetin -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Quercetin -- chemistry KW - Flavonoids -- administration & dosage KW - Flavonoids -- chemistry KW - Quercetin -- analogs & derivatives KW - Receptors, Aryl Hydrocarbon -- metabolism KW - Receptors, Aryl Hydrocarbon -- genetics KW - Receptors, Aryl Hydrocarbon -- deficiency KW - Flavonoids -- pharmacology KW - Flavonoids -- metabolism KW - Quercetin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69809985?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Biochemical+journal&rft.atitle=Dietary+flavonols+quercetin+and+kaempferol+are+ligands+of+the+aryl+hydrocarbon+receptor+that+affect+CYP1A1+transcription+differentially.&rft.au=Ciolino%2C+H+P%3BDaschner%2C+P+J%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1999-06-15&rft.volume=340+%28+Pt+3%29&rft.issue=&rft.spage=715&rft.isbn=&rft.btitle=&rft.title=The+Biochemical+journal&rft.issn=02646021&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-02 N1 - Date created - 1999-08-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nutr Cancer. 1993;20(1):21-9 [8415127] Carcinogenesis. 1994 Apr;15(4):725-32 [8149487] Anal Biochem. 1994 Oct;222(1):217-23 [7856852] Annu Rev Pharmacol Toxicol. 1995;35:307-40 [7598497] J Nutr. 1995 Jul;125(7):1911-22 [7616308] J Occup Environ Med. 1995 Jan;37(1):52-8 [7620943] Arch Biochem Biophys. 1995 Aug 20;321(2):405-12 [7646066] Eur J Pharmacol. 1995 Oct 6;293(3):191-205 [8666036] Carcinogenesis. 1996 Apr;17(4):877-9 [8625504] J Biol Chem. 1996 Feb 16;271(7):3952-8 [8632018] Mol Pharmacol. 1996 Jun;49(6):980-8 [8649358] Arch Biochem Biophys. 1996 Sep 1;333(1):170-8 [8806768] J Biol Chem. 1996 Oct 18;271(42):26261-6 [8824276] Biochem Pharmacol. 1996 Apr 26;51(8):1069-76 [8866829] Biochem Pharmacol. 1996 Apr 26;51(8):1077-87 [8866830] Biochem Biophys Res Commun. 1996 Dec 4;229(1):231-7 [8954111] Biochem Pharmacol. 1996 Dec 13;52(11):1787-803 [8986142] Free Radic Biol Med. 1997;22(5):749-60 [9119242] J Biol Chem. 1997 May 9;272(19):12705-13 [9139728] Drug Metab Dispos. 1997 May;25(5):617-22 [9152602] FEBS Lett. 1997 Nov 24;418(1-2):152-6 [9414116] Drug Metab Rev. 1997 Nov;29(4):1107-27 [9421687] Biomed Pharmacother. 1997;51(8):305-10 [9436520] Arch Toxicol Suppl. 1998;20:237-48 [9442297] Cancer Lett. 1997 Dec 9;120(2):213-6 [9461039] Biochem J. 1998 Mar 15;330 ( Pt 3):1173-8 [9494082] Mol Pharmacol. 1998 Mar;53(3):438-45 [9495809] Environ Health Perspect. 1998 Apr;106 Suppl 2:755-60 [9599727] Biochem Pharmacol. 1998 Jul 15;56(2):197-206 [9698073] Biochemistry. 1998 Aug 18;37(33):11508-15 [9708986] Arch Biochem Biophys. 1998 Sep 1;357(1):155-63 [9721195] J Biol Chem. 1994 Apr 22;269(16):11751-9 [7909315] Anal Biochem. 1976 May 7;72:248-54 [942051] World Rev Nutr Diet. 1976;24:117-91 [790781] Anal Biochem. 1985 Feb 1;144(2):371-84 [2986476] Arch Biochem Biophys. 1985 Jul;240(1):345-57 [3925883] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8044-8 [3464941] J Toxicol Environ Health. 1987;21(3):311-23 [3495667] Methods Enzymol. 1987;152:704-20 [2889129] Cancer Res. 1988 May 1;48(9):2361-5 [3128399] J Biol Chem. 1988 Nov 25;263(33):17221-4 [2846558] J Toxicol Environ Health. 1990;29(4):339-55 [2157855] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9543-7 [1658785] Carcinogenesis. 1992 Sep;13(9):1619-24 [1327572] J Biol Chem. 1994 Jul 22;269(29):19028-33 [8034660] Nucleic Acids Res. 1994 Aug 11;22(15):3038-44 [8065918] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of antihistamines on fenfluramine-induced depletion of indoles in the brain of rats. AN - 69764724; 10332805 AB - Various effects of chlorpheniramine (CPA), diphenhydramine (DIPH), tripelennamine (TRIP), and pyrilamine (PYRI) on fenfluramine (FEN)-induced depletion of serotonin in the brain of rats were observed to be dependent on body temperature. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, and striatum of rats treated with FEN (10 mg/kg, once or twice daily x 4 days) decreased to approximately 30% (P < 0.01) that of controls with no significant changes after CPA, DIPH, TRIP, and PYRI. Treatment with FEN plus CPA (5, 10, 20 mg/kg) and FEN plus DIPH (20 mg/kg), but not FEN plus TRIP (20 mg/kg) and FEN plus PYRI (20 mg/kg), increased brain serotonin levels 2- to 3-fold more than those treated with FEN plus saline. Treatment with FEN plus CPA and FEN plus DIPH, but not FEN plus TRIP and FEN plus PYRI, decreased rectal temperature with no significant change after FEN. The antihistamines alone decreased temperature at a 1-hour period and enhanced FEN-induced reduction in body weight. Possible mechanisms of the different effects of antihistamines on FEN-induced depletion of serotonin are discussed. JF - Synapse (New York, N.Y.) AU - Yeh, S Y AD - Molecular Neuropsychiatry Section, National Institute on Drug Abuse, National Institute of Health, Baltimore, Maryland 21224, USA. Y1 - 1999/06/15/ PY - 1999 DA - 1999 Jun 15 SP - 301 EP - 311 VL - 32 IS - 4 SN - 0887-4476, 0887-4476 KW - Biomarkers KW - 0 KW - Histamine H1 Antagonists KW - Fenfluramine KW - 2DS058H2CF KW - Serotonin KW - 333DO1RDJY KW - Chlorpheniramine KW - 3U6IO1965U KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Drug Interactions KW - Body Temperature -- drug effects KW - Body Weight -- drug effects KW - Male KW - Hydroxyindoleacetic Acid -- metabolism KW - Histamine H1 Antagonists -- pharmacology KW - Brain -- drug effects KW - Chlorpheniramine -- pharmacology KW - Brain -- metabolism KW - Fenfluramine -- pharmacology KW - Serotonin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69764724?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Synapse+%28New+York%2C+N.Y.%29&rft.atitle=Effects+of+antihistamines+on+fenfluramine-induced+depletion+of+indoles+in+the+brain+of+rats.&rft.au=Yeh%2C+S+Y&rft.aulast=Yeh&rft.aufirst=S&rft.date=1999-06-15&rft.volume=32&rft.issue=4&rft.spage=301&rft.isbn=&rft.btitle=&rft.title=Synapse+%28New+York%2C+N.Y.%29&rft.issn=08874476&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-08 N1 - Date created - 1999-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Convulsant actions of the neurosteroid pregnenolone sulfate in mice. AN - 69903607; 10411990 AB - Pregnenolone sulfate (PS) is an endogenous neurosteroid known to antagonize GABA(A) receptor-mediated inhibitory responses and potentiate NMDA receptor-mediated excitatory responses in vitro. To assess the actions of the steroid as a modulator of seizure susceptibility in vivo, PS (30-300 nmol) was administered intracerebroventricularly in mice. At doses of 50 to 150 nmol, PS elicited seizures characterized by head jerks, rearing and falling, severe forelimb and hindlimb clonus, opisthotonos and explosive running. The seizures increased in severity and frequency with time and eventually progressed to status epilepticus, tonic hindlimb extension and death. The doses producing convulsions in 50% (CD(50)) and 97% (CD(97)) of animals were 92 and 205 nmol, respectively. A subconvulsant dose of PS (50 nmol) significantly increased the convulsant potencies of systemically administered pentylenetetrazol (30-50 mg/kg) and NMDA (50-100 mg/kg). Systemically administered PS at doses as high as 100 mg/kg failed to induce seizures or alter the convulsant potencies of pentylenetetrazol and NMDA. Protection against PS (205 nmol)-induced seizures and lethality was conferred by the GABA(A) receptor positive allosteric modulators clonazepam and allopregnanolone, and by the NMDA receptor antagonists dizocilpine and (R)-CPP. The overall pharmacological profile suggests that the convulsant actions of PS are mediated predominantly via its effects on GABA(A) receptors, and also possibly by effects on NMDA receptors. Copyright 1999 Elsevier Science B.V. JF - Brain research AU - Kokate, T G AU - Juhng, K N AU - Kirkby, R D AU - Llamas, J AU - Yamaguchi, S AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 5N-250, Bethesda, MD 20892-1408, USA. Y1 - 1999/06/12/ PY - 1999 DA - 1999 Jun 12 SP - 119 EP - 124 VL - 831 IS - 1-2 SN - 0006-8993, 0006-8993 KW - Convulsants KW - 0 KW - Receptors, GABA-A KW - pregnenolone sulfate KW - 04Y4D91RG0 KW - N-Methylaspartate KW - 6384-92-5 KW - Pregnenolone KW - 73R90F7MQ8 KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Disease Susceptibility KW - Pentylenetetrazole -- toxicity KW - N-Methylaspartate -- toxicity KW - Receptors, GABA-A -- drug effects KW - Mice KW - Drug Synergism KW - Male KW - Injections, Intraventricular KW - Pregnenolone -- toxicity KW - Convulsants -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69903607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Convulsant+actions+of+the+neurosteroid+pregnenolone+sulfate+in+mice.&rft.au=Kokate%2C+T+G%3BJuhng%2C+K+N%3BKirkby%2C+R+D%3BLlamas%2C+J%3BYamaguchi%2C+S%3BRogawski%2C+M+A&rft.aulast=Kokate&rft.aufirst=T&rft.date=1999-06-12&rft.volume=831&rft.issue=1-2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-18 N1 - Date created - 1999-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 rats and B6C3F1 mice after oral administration. AN - 69834682; 10376886 AB - (5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of hexoses, is present in food and drink. Recent reports have shown HMF to be an in vitro mutagen after sulfate conjugation and to be a promoter as well as a weak initiator of colonic aberrant foci in rats. In order to investigate the metabolic activation further and to provide information for HMF toxicology studies, the disposition of [14C]-HMF has been investigated in male F344 rats and B6C3F1 mice following po administration of either 5, 10, 100, or 500 mg/kg. Tissue distribution results indicated that absorption of HMF was rapid in male rats and mice and that tissue concentrations in male mice at the earliest time point are not linearly proportional to dose. Excretion was primarily via the urine in both, with 60-80% of the administered dose excreted by this route in 48 h. Tissue/blood ratios of HMF-derived radioactivity were greater than 1 for liver and kidney. Three metabolites were identified and quantitated in urine. Formation of one of the metabolites, N-(5-hydroxymethyl-2-furoyl)glycine, was inversely proportional to dose in rats but not mice. None of the metabolites were sulfate conjugates nor likely to be formed from sulfate conjugates. There were relatively low levels of nonextractable radioactivity in liver, kidney, and intestines, indicating that some reactive intermediate(s) may be formed. JF - Journal of toxicology and environmental health. Part A AU - Godfrey, V B AU - Chen, L J AU - Griffin, R J AU - Lebetkin, E H AU - Burka, L T AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/06/11/ PY - 1999 DA - 1999 Jun 11 SP - 199 EP - 210 VL - 57 IS - 3 SN - 1528-7394, 1528-7394 KW - Carcinogens KW - 0 KW - Furaldehyde KW - DJ1HGI319P KW - Index Medicus KW - Rats KW - Hot Temperature KW - Animals KW - Rats, Inbred F344 KW - Food Contamination KW - Mice KW - Tissue Distribution KW - Male KW - Furaldehyde -- pharmacokinetics KW - Carcinogens -- metabolism KW - Carcinogens -- pharmacokinetics KW - Furaldehyde -- analogs & derivatives KW - Furaldehyde -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69834682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+toxicology+and+environmental+health.+Part+A&rft.atitle=Distribution+and+metabolism+of+%285-hydroxymethyl%29furfural+in+male+F344+rats+and+B6C3F1+mice+after+oral+administration.&rft.au=Godfrey%2C+V+B%3BChen%2C+L+J%3BGriffin%2C+R+J%3BLebetkin%2C+E+H%3BBurka%2C+L+T&rft.aulast=Godfrey&rft.aufirst=V&rft.date=1999-06-11&rft.volume=57&rft.issue=3&rft.spage=199&rft.isbn=&rft.btitle=&rft.title=Journal+of+toxicology+and+environmental+health.+Part+A&rft.issn=15287394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-30 N1 - Date created - 1999-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of critical, conserved vicinal aspartate residues in mammalian and bacterial ADP-ribosylarginine hydrolases. AN - 69808643; 10358013 AB - NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyze opposing arms of a putative ADP-ribosylation cycle. ADP-ribosylarginine hydrolases from mammalian tissues and Rhodospirillum rubrum exhibit three regions of similarity in deduced amino acid sequence. We postulated that amino acids in these consensus regions could be critical for hydrolase function. To test this hypothesis, hydrolase, cloned from rat brain, was expressed as a glutathione S-transferase fusion protein in Escherichia coli and purified by glutathione-Sepharose affinity chromatography. Conserved amino acids in each of these regions were altered by site-directed mutagenesis. Replacement of Asp-60 or Asp-61 with Ala, Gln, or Asn, but not Glu, significantly reduced enzyme activity. The double Asp-60 --> Glu/Asp-61 --> Glu mutant was inactive, as were Asp-60 --> Gln/Asp-61 --> Gln or Asp-60 --> Asn/Asp-61 --> Asn. The catalytically inactive single and double mutants appeared to retain conformation, since they bound ADP-ribose, a substrate analogue and an inhibitor of enzyme activity, with affinity similar to that of the wild-type hydrolase and with the expected stoichiometry of one. Replacing His-65, Arg-139, Asp-285, which are also located in the conserved regions, with alanine did not change specific activity. These data clearly show that the conserved vicinal aspartates 60 and 61 in rat ADP-ribosylarginine hydrolase are critical for catalytic activity, but not for high affinity binding of the substrate analogue, ADP-ribose. JF - The Journal of biological chemistry AU - Konczalik, P AU - Moss, J AD - Pulmonary-Critical Care Medicine Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892-1434, USA. konczalp@gwgate.nhlbi.nih.gov Y1 - 1999/06/11/ PY - 1999 DA - 1999 Jun 11 SP - 16736 EP - 16740 VL - 274 IS - 24 SN - 0021-9258, 0021-9258 KW - Recombinant Fusion Proteins KW - 0 KW - Adenosine Diphosphate Ribose KW - 20762-30-5 KW - Aspartic Acid KW - 30KYC7MIAI KW - Glycoside Hydrolases KW - EC 3.2.1.- KW - N-Glycosyl Hydrolases KW - EC 3.2.2.- KW - ADP-ribosylarginine hydrolase KW - EC 3.2.2.19 KW - Index Medicus KW - Recombinant Fusion Proteins -- metabolism KW - Rats KW - Brain -- enzymology KW - Animals KW - Protein Processing, Post-Translational KW - Rhodospirillum rubrum -- enzymology KW - Escherichia coli -- genetics KW - Amino Acid Sequence KW - Adenosine Diphosphate Ribose -- metabolism KW - Species Specificity KW - Mutation KW - Cloning, Molecular KW - Conserved Sequence KW - Glycoside Hydrolases -- metabolism KW - Glycoside Hydrolases -- genetics KW - Glycoside Hydrolases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69808643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+critical%2C+conserved+vicinal+aspartate+residues+in+mammalian+and+bacterial+ADP-ribosylarginine+hydrolases.&rft.au=Konczalik%2C+P%3BMoss%2C+J&rft.aulast=Konczalik&rft.aufirst=P&rft.date=1999-06-11&rft.volume=274&rft.issue=24&rft.spage=16736&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of stomach cancer in relation to consumption of cigarettes, alcohol, tea and coffee in Warsaw, Poland AN - 17305731; 4581403 AB - To identify reasons for the high incidence rates of stomach cancer in Poland, we conducted a population-based case-control study in Warsaw. Cases were residents aged 21 to 79 years who were newly diagnosed with stomach cancer between March 1, 1994, and April 30, 1997. Controls were randomly selected from Warsaw residents registered at the nationwide Polish Electronic System of Residence Evidency, frequency-matched to cases by age and sex. Information on demographic characteristics; consumption of cigarettes, alcohol, tea and coffee; diet; medical history; family history of cancer; occupational history; and living conditions during adolescence was elicited by trained interviewers using a structured questionnaire. Included were 464 cases (90% of eligible) and 480 controls (87% of eligible). Among men, the risk of stomach cancer was significantly elevated among current smokers but not among former smokers. Among women, an 80% increase in risk was observed in both current and former smokers but dose-response trends were less consistent than among men. Alcohol consumption was not clearly related to risk, and no association was found for drinking regular coffee or herbal tea or using milk/cream in coffee or tea. JF - International Journal of Cancer AU - Chow, W-H AU - Swanson, CA AU - Lissowska, J AU - Groves, F D AU - Sobin, L H AU - Nasierowska-Guttmejer, A AU - Radziszewski, J AU - Regula, J AU - Hsing, A W AU - Jagannatha, S AU - Zatonski, W AU - Blot, W J AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, choww@exchange.nih.gov Y1 - 1999/06/11/ PY - 1999 DA - 1999 Jun 11 SP - 871 EP - 876 VL - 81 IS - 6 SN - 0020-7136, 0020-7136 KW - Poland, Warsaw KW - coffee KW - tea KW - Risk Abstracts; Health & Safety Science Abstracts KW - Diets KW - Alcohol KW - Cancer KW - Cigarette smoking KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17305731?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Cancer&rft.atitle=Risk+of+stomach+cancer+in+relation+to+consumption+of+cigarettes%2C+alcohol%2C+tea+and+coffee+in+Warsaw%2C+Poland&rft.au=Chow%2C+W-H%3BSwanson%2C+CA%3BLissowska%2C+J%3BGroves%2C+F+D%3BSobin%2C+L+H%3BNasierowska-Guttmejer%2C+A%3BRadziszewski%2C+J%3BRegula%2C+J%3BHsing%2C+A+W%3BJagannatha%2C+S%3BZatonski%2C+W%3BBlot%2C+W+J&rft.aulast=Chow&rft.aufirst=W-H&rft.date=1999-06-11&rft.volume=81&rft.issue=6&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Cancer&rft.issn=00207136&rft_id=info:doi/10.1002%2F%28SICI%291097-0215%2819990611%2981%3A63.0.CO%3B2-%23 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Alcohol; Cancer; Cigarette smoking; Diets DO - http://dx.doi.org/10.1002/(SICI)1097-0215(19990611)81:6<871::AID-IJC6>3.0.CO;2-# ER - TY - JOUR T1 - Drug metabolism polymorphisms as modulators of cancer susceptibility AN - 18269940; 5328859 AB - Recently, several molecular genetic bases of polymorphic enzyme activities involved in drug activation and detoxification have been elucidated. Many molecular epidemiology studies based on these premises have sought to gather information on the association of genetically determined metabolic variants with different risks of environmentally induced cancer. While rare alterations of tumor suppressor genes dramatically raise cancer risk for the single affected subjects, far more common and less dramatic differences in genes encoding for drug metabolism enzymes can be responsible for a relatively small, but rather frequent increase of cancer risk at the population level. This increase could be especially important in specific cases of occupational, pharmacological or environmental exposure. Examination of the current literature reveals that the most extensively investigated metabolic polymorphisms are those of P450 1A1 and P450 2D6 cytochromes, glutathione S-transferases (GSTs; M1 and, to a lesser extent, M3, P1 and T1) and N -acetyltransferases (NATs; NAT1 and NAT2). Making reference to these enzymes, we have assayed the current knowledge on the relations among polymorphisms of human xenobiotic-metabolizing enzymes and cancer susceptibilities. We have found intriguing models of susceptibility toward different types of cancer. We have reviewed and commented these models on light of the complex balance among different enzyme activities that, in each individual, determines the degree of each cancer susceptibility. Moreover, we have found techniques of molecular genetic analysis, more suitable than previous ones on phenotypic expression, now allowing better means to detect individuals at risk of cancer. According to the models presently available, a systematic screening of individuals at risk seems to make sense only in situations of well defined carcinogenic exposures and when performed by the polymorphism analysis of coordinated enzyme activities concurring to the metabolism of the carcinogen(s) in question. Genetic polymorphism analysis can allow for the detection of patients more prone to some types of specific cancers, or to the adverse effects of specific pharmaceutical agents. Considering the increasingly confirmed double-edged sword nature of metabolism polymorphism (both wild-type and variant alleles can predispose to cancer, albeit in different situations of exposure), individual susceptibility to cancer should be monitored as a function of the nature, and mechanism of action, of the carcinogen(s) to which the individual under study is known to be exposed, and with reference to the main target organ of the considered type of exposure. JF - Mutation Research-Reviews in Mutation Research AU - Taningher, M AU - Malacarne, D AU - Izzotti, A AU - Ugolini, D AU - Parodi, S AD - National Cancer Institute (IST)/Department of Oncology, Biology and Genetics, University of Genoa, Largo R. Benzi No. 10, I-16132 Genoa, Italy Y1 - 1999/06/08/ PY - 1999 DA - 1999 Jun 08 SP - 227 EP - 261 PB - Elsevier Science B.V., P.O. Box 211 Amsterdam 1000 AE Netherlands, [mailto:nlinfo-f@elsevier.nl], [URL:http://www.elsevier.nl/] VL - 436 IS - 3 SN - 1383-5742, 1383-5742 KW - drug metabolism KW - metabolism polymorphisms KW - susceptibility KW - man KW - Genetics Abstracts; Toxicology Abstracts KW - Tumor suppressor genes KW - Gene polymorphism KW - Drug metabolism KW - Reviews KW - Enzymes KW - Pharmaceuticals KW - Cancer KW - X 24114:Metabolism KW - G 07470:Cytogenetics & general UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18269940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research-Reviews+in+Mutation+Research&rft.atitle=Drug+metabolism+polymorphisms+as+modulators+of+cancer+susceptibility&rft.au=Taningher%2C+M%3BMalacarne%2C+D%3BIzzotti%2C+A%3BUgolini%2C+D%3BParodi%2C+S&rft.aulast=Taningher&rft.aufirst=M&rft.date=1999-06-08&rft.volume=436&rft.issue=3&rft.spage=227&rft.isbn=&rft.btitle=&rft.title=Mutation+Research-Reviews+in+Mutation+Research&rft.issn=13835742&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Reviews; Pharmaceuticals; Enzymes; Cancer; Tumor suppressor genes; Drug metabolism; Gene polymorphism ER - TY - JOUR T1 - Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12- and IFN- gamma -dependent mechanisms AN - 17244023; 4534788 AB - Resistance to murine leishmaniasis correlates with development of a CD4 super(+) T helper 1 (Th1)-predominant immune response. To determine whether immunostimulatory CpG-containing oligodeoxynucleotides (CpG-ODN), known to promote a Th1 immune response, could provide protection from Leishmania infection, CpG-ODN and freeze-thawed (F/T) Leishmania major were coinjected intradermally into susceptible BALB/c mice. A Leishmania-specific Th1-predominant immune response was induced, and 40% of animals were protected from subsequent challenge with infectious organisms, with 0% protection of animals injected with F/T Leishmania organisms and PBS, F/T organisms and control ODN, or F/T organisms alone. More striking protection (65-95%) was seen in mice first infected with intact Leishmania organisms and then injected with CpG-ODN, either at the site of infection or at a remote site. To determine whether the therapeutic protection provided by CpG-ODN depended on IL-12 and IFN- gamma production, both IFN- gamma -deficient BALB/c mice and BALB/c mice treated with neutralizing anti-IL-12 mAb were first inoculated with Leishmania and then treated with either CpG-ODN, ODN, or PBS. None of these IFN- gamma -deficient mice survived (0/20, 0/20, and 0/20 respectively). Furthermore, neutralization of IL- 12 completely abolished the therapeutic protection provided by CpG-ODN (0/20 mice surviving). We conclude that immunostimulatory DNA sequences likely exert systemic effects via IL-12 and IFN- gamma - dependent mechanisms and hold considerable promise as both vaccine adjuvants and potential therapeutic agents in the prevention and treatment of leishmaniasis. JF - Proceedings of the National Academy of Sciences, USA AU - Walker, P S AU - Scharton-Kersten, T AU - Krieg, A M AU - Love-Homan, L AU - Rowton, ED AU - Udey, M C AU - Vogel, J C AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1908 USA, jonvogel@Box-j.nih.gov Y1 - 1999/06/08/ PY - 1999 DA - 1999 Jun 08 SP - 6970 EP - 6975 VL - 96 IS - 12 SN - 0027-8424, 0027-8424 KW - BALB/c mice KW - Leishmania major KW - gamma -Interferon KW - oligodeoxynucleotides KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Adjuvants KW - Lymphocytes T KW - Leishmaniasis KW - Immunostimulation KW - Vaccines KW - Helper cells KW - Interleukin 12 KW - K 03086:Immunology & vaccination KW - F 06807:Active immunization KW - F 06775:Chemokines KW - N 14250:Biological properties KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17244023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Immunostimulatory+oligodeoxynucleotides+promote+protective+immunity+and+provide+systemic+therapy+for+leishmaniasis+via+IL-12-+and+IFN-+gamma+-dependent+mechanisms&rft.au=Walker%2C+P+S%3BScharton-Kersten%2C+T%3BKrieg%2C+A+M%3BLove-Homan%2C+L%3BRowton%2C+ED%3BUdey%2C+M+C%3BVogel%2C+J+C&rft.aulast=Walker&rft.aufirst=P&rft.date=1999-06-08&rft.volume=96&rft.issue=12&rft.spage=6970&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Leishmania major; Leishmaniasis; Adjuvants; Interleukin 12; Vaccines; Immunostimulation; Lymphocytes T; Helper cells ER - TY - JOUR T1 - Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. AN - 69791213; 10347145 AB - In the nematode Caenorhabditis elegans, mutations of the insulin/insulin-like growth factor-1 receptor homologue Daf-2 gene cause developmental arrest at the dauer stage. The effect of Daf-2 mutations is counteracted by mutations in the Daf-16 gene, suggesting that Daf-16 is required for signaling by Daf-2. Daf-16 encodes a forkhead transcription factor. Based on sequence similarity, the FKHR genes are the likeliest mammalian Daf-16 homologues. FKHR proteins contain potential sites for phosphorylation by the serine/threonine kinase Akt. Because Akt is phosphorylated in response to insulin and has been implicated in a variety of insulin effects, we investigated whether insulin affects phosphorylation of FKHR. Insulin stimulated phosphorylation of endogenous FKHR and of a recombinant c-Myc/FKHR fusion protein transiently expressed in murine SV40-transformed hepatocytes. The effect of insulin was inhibited by wortmannin treatment, suggesting that PI 3-kinase activity is required for FKHR phosphorylation. Mutation of serine 253, located in a consensus Akt phosphorylation site at the carboxyl-terminal end of the forkhead domain, abolished the effect of insulin on FKHR phosphorylation. In contrast, mutation of two additional Akt phosphorylation sites, at amino acids threonine 24 or serine 316, did not abolish insulin-induced phosphorylation. These data indicate that FKHR may represent a distal effector of insulin action. JF - The Journal of biological chemistry AU - Nakae, J AU - Park, B C AU - Accili, D AD - Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06/04/ PY - 1999 DA - 1999 Jun 04 SP - 15982 EP - 15985 VL - 274 IS - 23 SN - 0021-9258, 0021-9258 KW - Androstadienes KW - 0 KW - Blood Proteins KW - Enzyme Inhibitors KW - FOXO4 protein, human KW - Insulin KW - Proto-Oncogene Proteins KW - Transcription Factors KW - Threonine KW - 2ZD004190S KW - Serine KW - 452VLY9402 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - AKT1 protein, human KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - Proto-Oncogene Proteins c-akt KW - wortmannin KW - XVA4O219QW KW - Index Medicus KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Threonine -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Humans KW - Proto-Oncogene Proteins -- metabolism KW - Liver -- metabolism KW - Mice KW - Serine -- metabolism KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Phosphorylation KW - Cells, Cultured KW - Liver -- drug effects KW - Simian virus 40 KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Consensus Sequence KW - Amino Acid Substitution KW - Androstadienes -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Insulin -- pharmacology KW - Blood Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69791213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Insulin+stimulates+phosphorylation+of+the+forkhead+transcription+factor+FKHR+on+serine+253+through+a+Wortmannin-sensitive+pathway.&rft.au=Nakae%2C+J%3BPark%2C+B+C%3BAccili%2C+D&rft.aulast=Nakae&rft.aufirst=J&rft.date=1999-06-04&rft.volume=274&rft.issue=23&rft.spage=15982&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF126056; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Naturally occurring CCR5 extracellular and transmembrane domain variants affect HIV-1 Co-receptor and ligand binding function. AN - 69787755; 10347178 AB - Analysis of CCR5 variants in human immunodeficiency virus, type 1 (HIV-1), high risk cohorts led to the identification of multiple single amino acid substitutions in the amino-terminal third of the HIV-1 co-receptor CCR5 suggesting the possibility of protective and permissive genotypes; unfortunately, the low frequency of these mutations did not led to correlation with function. Therefore, we used analytical methods to assess the functional and structural significance of six of these variant receptors in vitro. These studies showed three categories of effects on CCR5 function. 1) Mutations in the first extracellular domain of CCR5 severely reduce specific ligand binding and chemokine-induced chemotaxis. 2) An extracellular domain variant, A29S, when co-expressed with CD4, supported HIV-1 infection whereas the others do not. 3) The transmembrane region variants of CCR5 support monotropic HIV-1 infection that is blocked by addition of some receptor agonists. Mutations in the first and second transmembrane domains increase RANTES (regulated on activation normal T-cell expressed) binding affinity but did not affect MIP1beta binding affinity presumably based on differences in ligand-receptor interaction sites. Furthermore, the CCR5 transmembrane mutants do not respond to RANTES with the classical bell-shaped chemotactic response curve, suggesting that they are resistant to RANTES-induced desensitization. These data demonstrate that single amino acid changes in the extracellular domains of CCR5 can have profound effects on both HIV-1 co-receptor and specific ligand-induced functions, whereas mutations in the transmembrane domain only affect the response to chemokine ligands. JF - The Journal of biological chemistry AU - Howard, O M AU - Shirakawa, A K AU - Turpin, J A AU - Maynard, A AU - Tobin, G J AU - Carrington, M AU - Oppenheim, J J AU - Dean, M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. howardz@mail.ncifcrf.gov Y1 - 1999/06/04/ PY - 1999 DA - 1999 Jun 04 SP - 16228 EP - 16234 VL - 274 IS - 23 SN - 0021-9258, 0021-9258 KW - Anti-HIV Agents KW - 0 KW - Chemokine CCL4 KW - Chemokine CCL5 KW - Ligands KW - Macrophage Inflammatory Proteins KW - NSC 651016 KW - Naphthalenesulfonates KW - Receptors, CCR5 KW - Index Medicus KW - AIDS/HIV KW - Macrophage Inflammatory Proteins -- metabolism KW - Protein Structure, Secondary KW - Humans KW - Amino Acid Sequence KW - Chemokine CCL5 -- metabolism KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Transfection KW - Naphthalenesulfonates -- pharmacology KW - Anti-HIV Agents -- pharmacology KW - Molecular Sequence Data KW - Flow Cytometry KW - Cell Line KW - HIV-1 -- metabolism KW - Receptors, CCR5 -- genetics KW - Receptors, CCR5 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69787755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Naturally+occurring+CCR5+extracellular+and+transmembrane+domain+variants+affect+HIV-1+Co-receptor+and+ligand+binding+function.&rft.au=Howard%2C+O+M%3BShirakawa%2C+A+K%3BTurpin%2C+J+A%3BMaynard%2C+A%3BTobin%2C+G+J%3BCarrington%2C+M%3BOppenheim%2C+J+J%3BDean%2C+M&rft.aulast=Howard&rft.aufirst=O&rft.date=1999-06-04&rft.volume=274&rft.issue=23&rft.spage=16228&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of a disulfide cross-linking strategy to study muscarinic receptor structure and mechanisms of activation. AN - 69786298; 10347230 AB - To gain insight into the molecular architecture of the cytoplasmic surface of G protein-coupled receptors, we have developed a disulfide cross-linking strategy using the m3 muscarinic receptor as a model system. To facilitate the interpretation of disulfide cross-linking data, we initially generated a mutant m3 muscarinic receptor (referred to as m3'(3C)-Xa) in which most native Cys residues had been deleted or substituted with Ala or Ser (remaining Cys residues Cys-140, Cys-220, and Cys-532) and in which the central portion of the third intracellular loop had been replaced with a factor Xa cleavage site. Radioligand binding and second messenger assays showed that the m3'(3C)-Xa mutant receptor was fully functional. In the next step, pairs of Cys residues were reintroduced into the m3'(3C)-Xa construct, thus generating 10 double Cys mutant receptors. All 10 mutant receptors contained a Cys residue at position 169 at the beginning of the second intracellular loop and a second Cys within the C-terminal portion of the third intracellular loop, at positions 484-493. Radioligand binding studies and phosphatidylinositol assays indicated that all double Cys mutant receptors were properly folded. Membrane lysates prepared from COS-7 cells transfected with the different mutant receptor constructs were incubated with factor Xa protease and the oxidizing agent Cu(II)-(1,10-phenanthroline)3, and the formation of intramolecular disulfide bonds between juxtaposed Cys residues was monitored by using a combined immunoprecipitation/immunoblotting strategy. To our surprise, efficient disulfide cross-linking was observed with 8 of the 10 double Cys mutant receptors studied (Cys-169/Cys-484 to Cys-491), suggesting that the intracellular m3 receptor surface is characterized by pronounced backbone fluctuations. Moreover, [35S]guanosine 5'-3-O-(thio)triphosphate binding assays indicated that the formation of intramolecular disulfide cross-links prevented or strongly inhibited receptor-mediated G protein activation, suggesting that the highly dynamic character of the cytoplasmic receptor surface is a prerequisite for efficient receptor-G protein interactions. This is the first study using a disulfide mapping strategy to examine the three-dimensional structure of a hormone-activated G protein-coupled receptor. JF - The Journal of biological chemistry AU - Zeng, F Y AU - Hopp, A AU - Soldner, A AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06/04/ PY - 1999 DA - 1999 Jun 04 SP - 16629 EP - 16640 VL - 274 IS - 23 SN - 0021-9258, 0021-9258 KW - Disulfides KW - 0 KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Factor Xa KW - EC 3.4.21.6 KW - Index Medicus KW - Rats KW - Mutagenesis, Site-Directed KW - Animals KW - Protein Structure, Secondary KW - Factor Xa -- metabolism KW - COS Cells KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Protein Conformation KW - Binding Sites KW - Receptors, Muscarinic -- genetics KW - Receptors, Muscarinic -- chemistry KW - Disulfides -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69786298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Use+of+a+disulfide+cross-linking+strategy+to+study+muscarinic+receptor+structure+and+mechanisms+of+activation.&rft.au=Zeng%2C+F+Y%3BHopp%2C+A%3BSoldner%2C+A%3BWess%2C+J&rft.aulast=Zeng&rft.aufirst=F&rft.date=1999-06-04&rft.volume=274&rft.issue=23&rft.spage=16629&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutational analysis of p73 and p53 in human cancer cell lines. AN - 69811291; 10362363 AB - p73 is a candidate tumor suppressor gene with substantial DNA and protein homology to the p53 tumor suppressor gene. We have investigated two hypotheses: (a) p73 is mutated in diverse types of human cancer, and (b) p73 is functionally redundant with p53 in carcinogenesis so that mutations would be exclusive in these two genes. The entire coding region and intronic splice junctions of p73 were examined in 54 cancer cell lines. Three lung cancer cell lines contained mutations that affected the amino acid sequence. One amino acid substitution was in a region with homology to the specific DNA binding region of p53 and two microdeletions were outside the region of homology. Two of the cell lines with p73 mutations also carried p53 mutations. Although our results are inconsistent with the two hypotheses tested, p73 mutations may contribute infrequently to the molecular pathogenesis of human lung cancer. JF - Oncogene AU - Yoshikawa, H AU - Nagashima, M AU - Khan, M A AU - McMenamin, M G AU - Hagiwara, K AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/06/03/ PY - 1999 DA - 1999 Jun 03 SP - 3415 EP - 3421 VL - 18 IS - 22 SN - 0950-9232, 0950-9232 KW - DNA-Binding Proteins KW - 0 KW - Nuclear Proteins KW - Tumor Protein p73 KW - Tumor Suppressor Protein p53 KW - Tumor Suppressor Proteins KW - p73 protein, human KW - Index Medicus KW - Polymerase Chain Reaction KW - Tumor Cells, Cultured KW - Humans KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Introns KW - Lung Neoplasms -- genetics KW - Sequence Analysis, DNA KW - Polymorphism, Single-Stranded Conformational KW - Nuclear Proteins -- genetics KW - Genes, Tumor Suppressor KW - DNA-Binding Proteins -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Mutation KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69811291?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Mutational+analysis+of+p73+and+p53+in+human+cancer+cell+lines.&rft.au=Yoshikawa%2C+H%3BNagashima%2C+M%3BKhan%2C+M+A%3BMcMenamin%2C+M+G%3BHagiwara%2C+K%3BHarris%2C+C+C&rft.aulast=Yoshikawa&rft.aufirst=H&rft.date=1999-06-03&rft.volume=18&rft.issue=22&rft.spage=3415&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-28 N1 - Date created - 1999-06-28 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF077620; GENBANK; AF077622; AF077621; AF077624; AF077623; AF077626; AF077625; AF077627; AF077628; AF077618; AF077619; AF077616; AF077617 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Laryngeal long latency response conditioning in abductor spasmodic dysphonia. AN - 85306572; pmid-10378532 AB - Previously, we demonstrated that patients with adductor spasmodic dysphonia (ADSD) have a disinhibition of laryngeal responses to sensory input. In this study, sensorimotor responses to stimulation of the superior laryngeal nerve were compared between 10 subjects with abductor spasmodic dysphonia (ABSD) and 15 normal volunteers. The groups had similar latency and frequency characteristics of their unconditioned adductor responses (p>.05). The conditioned R1 (early) responses of the subjects with ABSD were greater and more variable in amplitude than those of the normal volunteers (p< or =.008). Similar R2 (late) conditioning effects were found in both groups, with a nonsignificant trend toward reduced inhibition of contralateral R2 responses at lower interstimulus intervals (p = .01) in the patient group. Thus, inhibitory mechanisms that modulate the R1 laryngeal sensorimotor pathway in the brain stem may be abnormal in subjects with ABSD. Abnormal modulation of laryngeal sensorimotor responses seems present in both types of spasmodic dysphonia. JF - The Annals of otology, rhinology, and laryngology AU - Deleyiannis, F W AU - Gillespie, M AU - Bielamowicz, S AU - Yamashita, T AU - Ludlow, C L AD - Voice and Speech Section, Division of Intramural Research, National Institute on Deafness and Other Communication Disorders, Bethesda, Maryland 20892-1416, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 612 EP - 619 VL - 108 IS - 6 SN - 0003-4894, 0003-4894 KW - Abridged Index Medicus; Index Medicus KW - National Library of Medicine KW - Voice Disorders -- etiology KW - Humans KW - Phonetics KW - Voice Disorders -- diagnosis KW - Fiber Optic Technology -- methods KW - Voice Disorders -- physiopathology KW - Electromyography -- methods KW - Adult KW - Laryngoscopy -- methods KW - Middle Aged KW - Time Factors KW - Male KW - Female KW - Laryngeal Muscles -- physiopathology KW - Conditioning (Psychology) -- physiology KW - Laryngeal Nerves -- physiopathology KW - Spasm -- diagnosis KW - Spasm -- physiopathology KW - Spasm -- complications KW - Reaction Time -- physiology KW - Laryngeal Muscles -- innervation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85306572?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.atitle=Laryngeal+long+latency+response+conditioning+in+abductor+spasmodic+dysphonia.&rft.au=Deleyiannis%2C+F+W%3BGillespie%2C+M%3BBielamowicz%2C+S%3BYamashita%2C+T%3BLudlow%2C+C+L&rft.aulast=Deleyiannis&rft.aufirst=F&rft.date=1999-06-01&rft.volume=108&rft.issue=6&rft.spage=612&rft.isbn=&rft.btitle=&rft.title=The+Annals+of+otology%2C+rhinology%2C+and+laryngology&rft.issn=00034894&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Otx1 and Otx2 activities are required for the normal development of the mouse inner ear. AN - 85271728; pmid-10225993 AB - The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle (Otd) gene in Drosophila. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. Paint-filled membranous labyrinths of Otx1-/- mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Defects in the shape of the saccule and cochlea were variable in Otx1-/- mice and were much more severe in an Otx1-/-;Otx2(+/)- background. Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent. In addition, the maculae of the utricle and saccule were partially fused. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1-/- mutants were rescued. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs. JF - Development (Cambridge, England) AU - Morsli, H AU - Tuorto, F AU - Choo, D AU - Postiglione, M P AU - Simeone, A AU - Wu, Doris Kar-Wah AD - National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA.; National Institute on Deafness and Other Communication Disorders PY - 1999 SP - 2335 EP - 2343 VL - 126 IS - 11 SN - 0950-1991, 0950-1991 KW - Saccule and Utricle KW - Body Patterning KW - Labyrinth KW - Human KW - Animal KW - Mice KW - Nerve Tissue Proteins KW - Mice, Knockout KW - Phenotype KW - RNA, Messenger KW - Intramolecular Oxidoreductases KW - Bone Morphogenetic Proteins KW - Mutation KW - Trans-Activators KW - Gene Expression Regulation, Developmental UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85271728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Development+%28Cambridge%2C+England%29&rft.atitle=Otx1+and+Otx2+activities+are+required+for+the+normal+development+of+the+mouse+inner+ear.&rft.au=Morsli%2C+H%3BTuorto%2C+F%3BChoo%2C+D%3BPostiglione%2C+M+P%3BSimeone%2C+A%3BWu%2C+Doris+Kar-Wah&rft.aulast=Morsli&rft.aufirst=H&rft.date=1999-06-01&rft.volume=126&rft.issue=11&rft.spage=2335&rft.isbn=&rft.btitle=&rft.title=Development+%28Cambridge%2C+England%29&rft.issn=09501991&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - GABAA receptor subunit composition and functional properties of Cl- channels with differential sensitivity to zolpidem in embryonic rat hippocampal cells. AN - 85270186; pmid-10366626 AB - Using flow cytometry in conjunction with a voltage-sensitive fluorescent indicator dye (oxonol), we have identified and separated embryonic hippocampal cells according to the sensitivity of their functionally expressed GABAA receptors to zolpidem. Immunocytochemical and RT-PCR analysis of sorted zolpidem-sensitive (ZS) and zolpidem-insensitive (ZI) subpopulations identified ZS cells as postmitotic, differentiating neurons expressing alpha2, alpha4, alpha5, beta1, beta2, beta3, gamma1, gamma2, and gamma3 GABAA receptor subunits, whereas the ZI cells were neuroepithelial cells or newly postmitotic neurons, expressing predominantly alpha4, alpha5, beta1, and gamma2 subunits. Fluctuation analyses of macroscopic Cl- currents evoked by GABA revealed three kinetic components of GABAA receptor/Cl- channel activity in both subpopulations. We focused our study on ZI cells, which exhibited a limited number of subunits and functional channels, to directly correlate subunit composition with channel properties. Biophysical analyses of GABA-activated Cl- currents in ZI cells revealed two types of receptor-coupled channel properties: one comprising short-lasting openings, high affinity for GABA, and low sensitivity to diazepam, and the other with long-lasting openings, low affinity for GABA, and high sensitivity to diazepam. Both types of channel activity were found in the same cell. Channel kinetics were well modeled by fitting dwell time distributions to biliganded activation and included two open and five closed states. We propose that short- and long-lasting openings correspond to GABAA receptor/Cl- channels containing alpha4beta1gamma2 and alpha5beta1gamma2 subunits, respectively. JF - The Journal of Neuroscience AU - Maric, D AU - Maric, I AU - Wen, X AU - Fritschy, J M AU - Sieghart, W AU - Barker, J L AU - Serafini, R AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1999 SP - 4921 EP - 4937 VL - 19 IS - 12 SN - 1529-2401, 1529-2401 KW - Fetus KW - Receptors, GABA-A KW - Hippocampus KW - Diazepam KW - GABA Modulators KW - Animal KW - Gene Expression KW - Cell Differentiation KW - Pyridines KW - Reverse Transcriptase Polymerase Chain Reaction KW - Pregnancy KW - Rats KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - gamma-Aminobutyric Acid KW - Kinetics KW - Neurons KW - Hypnotics and Sedatives KW - Membrane Potentials KW - Flow Cytometry KW - Protein Structure, Tertiary KW - Chloride Channels KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85270186?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+Neuroscience&rft.atitle=GABAA+receptor+subunit+composition+and+functional+properties+of+Cl-+channels+with+differential+sensitivity+to+zolpidem+in+embryonic+rat+hippocampal+cells.&rft.au=Maric%2C+D%3BMaric%2C+I%3BWen%2C+X%3BFritschy%2C+J+M%3BSieghart%2C+W%3BBarker%2C+J+L%3BSerafini%2C+R&rft.aulast=Maric&rft.aufirst=D&rft.date=1999-06-01&rft.volume=19&rft.issue=12&rft.spage=4921&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+Neuroscience&rft.issn=15292401&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Histological changes in TSH-dependent tumours of the thyroid gland during serial transplantation in Fischer 344 rats. AN - 70005058; 10469271 AB - Transplantable tumours were induced in the thyroids of Fischer 344 rats fed thiouracil (TU) in a moderately low iodine diet for 8-13 months. Pieces of hyperplastic thyroid were implanted subcutaneously into rats fed a TU containing diet. Almost all implants gave rise to very small vascularized transplants but there were three significantly larger, pieces of which were transplanted again and gave rise to the tumour lines. From the third transplantation generation on, pieces of tumours were implanted into rats treated to have elevated circulating thyrotropin and a group fed a high iodine diet. With some exceptions, the implants grew only in rats fed the TU or a low iodine diet and yielded TSH-dependent tumours. Almost all the tumours observed initially were papillary, and most of the remainder had colloid-filled follicles bounded by columnar cells. One line of tumours was of the latter type for eight generations. The others had more complex histories, in which there were sublines that were papillary for eight or nine generations, whereas, others became progressively more cellular or follicular, and more heterogeneous with respect to histological types present per section at rates that varied with the subline. The large number of population doublings necessary to make a one gram tumour from a single original tumour cell indicates that the cells of dependent papillary tumours were immortalized. JF - International journal of experimental pathology AU - Wollman, S H AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 151 EP - 167 VL - 80 IS - 3 SN - 0959-9673, 0959-9673 KW - Carcinogens KW - 0 KW - Thiouracil KW - 59X161SCYL KW - Thyrotropin KW - 9002-71-5 KW - Index Medicus KW - Rats KW - Pedigree KW - Neoplasm Transplantation KW - Animals KW - Rats, Inbred F344 KW - Hyperplasia KW - Cell Transformation, Neoplastic -- pathology KW - Thyroid Gland -- pathology KW - Neovascularization, Pathologic KW - Male KW - Female KW - Neoplasms, Hormone-Dependent -- blood supply KW - Neoplasms, Hormone-Dependent -- physiopathology KW - Neoplasms, Hormone-Dependent -- pathology KW - Thyroid Neoplasms -- physiopathology KW - Thyroid Neoplasms -- pathology KW - Thyrotropin -- physiology KW - Thyroid Neoplasms -- blood supply UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70005058?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+experimental+pathology&rft.atitle=Histological+changes+in+TSH-dependent+tumours+of+the+thyroid+gland+during+serial+transplantation+in+Fischer+344+rats.&rft.au=Wollman%2C+S+H&rft.aulast=Wollman&rft.aufirst=S&rft.date=1999-06-01&rft.volume=80&rft.issue=3&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=International+journal+of+experimental+pathology&rft.issn=09599673&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-23 N1 - Date created - 1999-12-23 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Horm Res. 1997;47(4-6):145-57 [9167946] Biochim Biophys Acta. 1989 Feb;948(3):305-26 [2465781] Science. 1997 Nov 21;278(5342):1481,1483 [9411767] Science. 1951 Jul 13;114(2950):44-6 [14854897] J Natl Cancer Inst. 1961 Feb;26:473-87 [13786423] Recent Prog Horm Res. 1963;19:579-618 [14284032] Cancer. 1966 Aug;19(8):1063-80 [5912323] Cancer Res. 1967 Oct;27(10):1831-42 [6064960] Am J Pathol. 1976 Nov;85(2):317-32 [998724] J Natl Cancer Inst. 1976 Oct;57(4):861-4 [1003533] Am J Pathol. 1978 Dec;93(3):639-54 [717541] Endocrinology. 1978 Dec;103(6):2306-14 [748050] J Endocrinol. 1982 Jul;94(1):131-40 [7047666] Cancer. 1983 Nov 1;52(9):1720-7 [6616422] Endocrinology. 1985 Feb;116(2):611-5 [3967622] Cell Tissue Kinet. 1985 Sep;18(5):467-73 [4028106] Cancer Res. 1986 Feb;46(2):877-83 [3940650] Cancer Res. 1987 Mar 15;47(6):1646-51 [3815361] Endocrinology. 1987 May;120(5):1758-64 [3569110] Am J Pathol. 1989 Jan;134(1):141-7 [2913822] Science. 1997 Sep 26;277(5334):1948-9 [9333948] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Similarities between the pathogenesis of and immunity to diphtheria and pertussis: the complex nature of serum antitoxin-induced immunity to these two diseases. AN - 69959249; 10447032 AB - Despite data from animal studies, seroepidemiological surveys, and controlled clinical trials, skepticism persists about immunity to pertussis conferred by serum IgG neutralizing antibodies (antitoxin). This is largely prompted by the absence of a "protective" level of antitoxin. Examination of the similarities between the pathogenesis and immunity to pertussis and diphtheria provides an explanation for this dilemma. As with pertussis, diphtheria toxoid vaccination confers only approximately 70% immunity on an individual basis, individuals with protective levels of antitoxin may contract diphtheria, and about 50% of the entire population, especially adults, have less than protective levels of antitoxin. The virtual disappearance of diphtheria followed vaccination of the entire population with diphtheria toxoid, which blocked transmission of toxigenic Corynebacterium diphtheriae and thus reduced the pathogen to almost undetectable levels. The individual and community-based immunity induced by diphtheria toxoid, we hypothesize, is similar to that of pertussis and pertussis toxoid. JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America AU - Schneerson, R AD - Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - S136 EP - S139 VL - 28 Suppl 2 SN - 1058-4838, 1058-4838 KW - Antitoxins KW - 0 KW - Diphtheria Toxoid KW - Pertussis Vaccine KW - Index Medicus KW - Diphtheria Toxoid -- immunology KW - Humans KW - Antitoxins -- blood KW - Pertussis Vaccine -- immunology KW - Pertussis Vaccine -- standards KW - Diphtheria -- immunology KW - Whooping Cough -- prevention & control KW - Whooping Cough -- immunology KW - Diphtheria -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69959249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.atitle=Similarities+between+the+pathogenesis+of+and+immunity+to+diphtheria+and+pertussis%3A+the+complex+nature+of+serum+antitoxin-induced+immunity+to+these+two+diseases.&rft.au=Schneerson%2C+R&rft.aulast=Schneerson&rft.aufirst=R&rft.date=1999-06-01&rft.volume=28+Suppl+2&rft.issue=&rft.spage=S136&rft.isbn=&rft.btitle=&rft.title=Clinical+infectious+diseases+%3A+an+official+publication+of+the+Infectious+Diseases+Society+of+America&rft.issn=10584838&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-02 N1 - Date created - 1999-11-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Building a network of research in children's environmental health. AN - 69931128; 10346987 JF - Environmental health perspectives AU - Dearry, A D AU - Collman, G W AU - Saint, C AU - Fields, N AU - Redd, S AD - Division of Extramural Research and Training, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 391 EP - 392 VL - 107 Suppl 3 SN - 0091-6765, 0091-6765 KW - Index Medicus KW - United States KW - United States Environmental Protection Agency KW - Government Agencies -- organization & administration KW - Centers for Disease Control and Prevention (U.S.) KW - Humans KW - Environmental Exposure KW - Child KW - Universities KW - Environmental Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69931128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Building+a+network+of+research+in+children%27s+environmental+health.&rft.au=Dearry%2C+A+D%3BCollman%2C+G+W%3BSaint%2C+C%3BFields%2C+N%3BRedd%2C+S&rft.aulast=Dearry&rft.aufirst=A&rft.date=1999-06-01&rft.volume=107+Suppl+3&rft.issue=&rft.spage=391&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-08-29 N1 - Date created - 2000-08-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gel electrophoretic distinction between toxic and nontoxic forms of beta-amyloid (1-40). AN - 69916846; 10424461 AB - The in vitro toxicity of synthetic beta-amyloid (1-40) correlates with its binding to Congo red (CR). Potentially, therefore, CR binding to the beta-amyloid containing neuritic plaques in Alzheimer's disease could be used diagnostically. Using polyacrylamide under nondenaturing conditions, the present study shows that both CR binding and nonbinding synthetic beta-amyloid exhibits multiple charge-isomeric and size-isomeric species. The CR binding species exhibit values of free electrophoretic mobility, related to the surface charge density of the protein, which are less than those of the CR non-binding species within 95% confidence limits. Since surface net charge and solubility are correlated, the decreased solubility of the CR binding species may be responsible for the relative abundance and CR binding of beta-amyloid in the neuritic plaques of Alzheimer patients. JF - Electrophoresis AU - Brining, S K AU - Chen, N AU - Yi, D AU - Chrambach, A AD - Section on Macromolecular Analysis, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1580, USA. acc@cu.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1398 EP - 1402 VL - 20 IS - 7 SN - 0173-0835, 0173-0835 KW - Amyloid beta-Peptides KW - 0 KW - Peptide Fragments KW - amyloid beta-protein (1-40) KW - Congo Red KW - 3U05FHG59S KW - Index Medicus KW - Solubility KW - Hydrogen-Ion Concentration KW - Humans KW - Temperature KW - Isomerism KW - Electrophoresis, Capillary -- methods KW - Alzheimer Disease -- diagnosis KW - Congo Red -- analysis KW - Peptide Fragments -- chemistry KW - Electrophoresis, Polyacrylamide Gel -- methods KW - Amyloid beta-Peptides -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69916846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Electrophoresis&rft.atitle=Gel+electrophoretic+distinction+between+toxic+and+nontoxic+forms+of+beta-amyloid+%281-40%29.&rft.au=Brining%2C+S+K%3BChen%2C+N%3BYi%2C+D%3BChrambach%2C+A&rft.aulast=Brining&rft.aufirst=S&rft.date=1999-06-01&rft.volume=20&rft.issue=7&rft.spage=1398&rft.isbn=&rft.btitle=&rft.title=Electrophoresis&rft.issn=01730835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-20 N1 - Date created - 1999-10-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of a transgenic mouse model for carcinogenesis bioassays: evaluation of chemically induced skin tumors in Tg.AC mice. AN - 69913563; 10416269 AB - Transgenic rodent models have emerged as potentially useful tools in the assessment of drug and chemical safety. The transgenic Tg.AC mouse carries an inducible v-Ha-ras oncogene that imparts the characteristic of genetically initiated skin to these animals. The induction of epidermal papillomas in the area of topically applied chemical agents, for duration of not more than 26 weeks, acts as a reporter phenotype that defines the activity of the test article. We describe here the activity of six chemicals that have been previously characterized for activity in the standard 2-year bioassay conducted by the National Toxicology Program (NTP). Homozygous female Tg.AC mice were treated with benzene (BZ), benzethonium chloride (BZTC), o-benzyl-p-chlorophenol (BCP), 2-chloroethanol (2-CE), lauric acid diethanolamine (LADA) and triethanolamine (TEA). BZ and LADA induced skin papillomas in a dose-dependent manner, while BCP induced papillomas only at the highest dose. BZTC, 2-CE, and TEA exhibited no activity. The correspondence of chemical activity in Tg.AC mice with that in the 2-year bioassay was high. A comparison of responsiveness to BZ and LADA was made between hemizygous and homozygous female Tg.AC mice. Both genotypes appear to be equally sensitive to maximum doses of active compounds. The results reported here indicate that the Tg.AC transgenic mouse model can discriminate between carcinogens and noncarcinogens and that both mutagenic and nonmutagenic chemicals can be detected. These studies provide support for the adjunctive use of the Tg.AC transgenic mouse skin tumor model in drug and chemical safety assessment and for the prediction of the carcinogenic potential of chemicals. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Spalding, J W AU - French, J E AU - Tice, R R AU - Furedi-Machacek, M AU - Haseman, J K AU - Tennant, R W AD - Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. spalding@niehs.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 241 EP - 254 VL - 49 IS - 2 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Index Medicus KW - Animals KW - Homozygote KW - Survival Rate KW - Dose-Response Relationship, Drug KW - Mice KW - Species Specificity KW - Pharmacogenetics KW - Female KW - Skin Neoplasms -- chemically induced KW - Carcinogens -- toxicity KW - Carcinogenicity Tests -- methods KW - Mice, Transgenic KW - Papilloma -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69913563?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Development+of+a+transgenic+mouse+model+for+carcinogenesis+bioassays%3A+evaluation+of+chemically+induced+skin+tumors+in+Tg.AC+mice.&rft.au=Spalding%2C+J+W%3BFrench%2C+J+E%3BTice%2C+R+R%3BFuredi-Machacek%2C+M%3BHaseman%2C+J+K%3BTennant%2C+R+W&rft.aulast=Spalding&rft.aufirst=J&rft.date=1999-06-01&rft.volume=49&rft.issue=2&rft.spage=241&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-13 N1 - Date created - 1999-10-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Direct energy transfer to study the 3D structure of non-native proteins: AGH complex in molten globule state of apomyoglobin. AN - 69866263; 10388845 AB - The direct energy transfer technique was modified and applied to probe the relative localization of apomyoglobin A-, G- and H-helixes, which are partly protected from deuterium exchange in the equilibrium molten globule state and in the molten globule-like kinetic intermediate. The non-radiative transfer of tryptophan electronic energy to 3-nitrotyrosine was studied in different conformational states of apomyoglobin (native, molten globule, unfolded) and interpreted in terms of average distances between groups of the protein chain. The experimental data show that the distance between the middle of A-helix and the N-terminus of G-helix as well as the distance between the middle of the A-helix and the C-terminus of the H-helix in the molten globule state are close to those in the native state. This is a strong argument in favor of similarity of the overall architecture of the molten globule and native states. JF - Protein engineering AU - Tcherkasskaya, O AU - Ptitsyn, O B AD - Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-5677, USA.otcherka@lmmb.nci.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 485 EP - 490 VL - 12 IS - 6 SN - 0269-2139, 0269-2139 KW - Apoproteins KW - 0 KW - Myoglobin KW - apomyoglobin KW - 3-nitrotyrosine KW - 3604-79-3 KW - Tyrosine KW - 42HK56048U KW - Tryptophan KW - 8DUH1N11BX KW - Tetranitromethane KW - K1G7CKU98F KW - Index Medicus KW - Tyrosine -- chemistry KW - Animals KW - Protein Structure, Secondary KW - Tetranitromethane -- chemistry KW - Spectrometry, Fluorescence KW - Energy Transfer KW - Models, Molecular KW - Protein Folding KW - Horses KW - Spectrophotometry KW - Tyrosine -- analogs & derivatives KW - Tryptophan -- chemistry KW - Protein Conformation KW - Apoproteins -- chemistry KW - Myoglobin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69866263?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+engineering&rft.atitle=Direct+energy+transfer+to+study+the+3D+structure+of+non-native+proteins%3A+AGH+complex+in+molten+globule+state+of+apomyoglobin.&rft.au=Tcherkasskaya%2C+O%3BPtitsyn%2C+O+B&rft.aulast=Tcherkasskaya&rft.aufirst=O&rft.date=1999-06-01&rft.volume=12&rft.issue=6&rft.spage=485&rft.isbn=&rft.btitle=&rft.title=Protein+engineering&rft.issn=02692139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - RNA polymerase II targets pre-mRNA splicing factors to transcription sites in vivo. AN - 69865702; 10394358 AB - Biochemical evidence indicates that pre-mRNA splicing factors physically interact with the C-terminal domain of the largest subunit of RNA polymerase II. We have investigated the in vivo function of this interaction. In mammalian cells, truncation of the CTD of RNA pol II LS prevents the targeting of the splicing machinery to a transcription site. In the absence of the CTD, pre-mRNA splicing is severely reduced. The presence of unspliced RNA alone is not sufficient for the accumulation of splicing factors at the transcription site, nor for its efficient splicing. Our results demonstrate a critical role for the CTD of RNA pol II LS in the intranuclear targeting of splicing factors to transcription sites in vivo. JF - Molecular cell AU - Misteli, T AU - Spector, D L AD - National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mistelit@mail.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 697 EP - 705 VL - 3 IS - 6 SN - 1097-2765, 1097-2765 KW - Amanitins KW - 0 KW - Nuclear Proteins KW - Phosphoproteins KW - RNA-Binding Proteins KW - Ribonucleoproteins KW - Ribonucleoproteins, Small Nuclear KW - SRSF3 protein, human KW - SRSF2 protein, human KW - 147153-65-9 KW - Serine-Arginine Splicing Factors KW - 170974-22-8 KW - Dichlororibofuranosylbenzimidazole KW - 53-85-0 KW - RNA KW - 63231-63-0 KW - RNA Polymerase II KW - EC 2.7.7.- KW - Index Medicus KW - Animals KW - RNA-Binding Proteins -- analysis KW - Phosphoproteins -- chemistry KW - RNA-Binding Proteins -- genetics KW - RNA-Binding Proteins -- metabolism KW - Cell Nucleus -- metabolism KW - Humans KW - Cell Nucleus -- chemistry KW - Ribonucleoproteins, Small Nuclear -- metabolism KW - Rats KW - Exons -- genetics KW - RNA -- metabolism KW - Phosphoproteins -- analysis KW - Sequence Deletion KW - Phosphoproteins -- metabolism KW - RNA -- genetics KW - RNA Splicing -- drug effects KW - Phosphoproteins -- genetics KW - HeLa Cells KW - Dichlororibofuranosylbenzimidazole -- pharmacology KW - RNA -- analysis KW - RNA-Binding Proteins -- chemistry KW - Binding Sites KW - Phosphorylation -- drug effects KW - RNA Splicing -- genetics KW - Amanitins -- pharmacology KW - Protein Binding -- drug effects KW - Nuclear Proteins -- analysis KW - RNA Polymerase II -- metabolism KW - Transcription, Genetic -- drug effects KW - Nuclear Proteins -- genetics KW - RNA Polymerase II -- genetics KW - Transcription, Genetic -- genetics KW - Spliceosomes -- genetics KW - RNA Polymerase II -- chemistry KW - Nuclear Proteins -- chemistry KW - Nuclear Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69865702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+cell&rft.atitle=RNA+polymerase+II+targets+pre-mRNA+splicing+factors+to+transcription+sites+in+vivo.&rft.au=Misteli%2C+T%3BSpector%2C+D+L&rft.aulast=Misteli&rft.aufirst=T&rft.date=1999-06-01&rft.volume=3&rft.issue=6&rft.spage=697&rft.isbn=&rft.btitle=&rft.title=Molecular+cell&rft.issn=10972765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High inter- and intrapatient variation in 5-fluorouracil plasma concentrations during a prolonged drug infusion. AN - 69860264; 10389918 AB - The purpose of the study was to examine inter- and intrapatient variation in 5-fluorouracil (5-FU) plasma concentrations in adult cancer patients receiving a 3-day drug infusion. Fourteen patients received 1266 mg/m2 N-(phosphonacetyl)-L-aspartate (PALA) infused i.v. over 15 min on day 1, followed immediately by a loading dose of 500 mg/m2 calcium leucovorin over 30 min. Then a prolonged infusion of leucovorin at 500 mg/m2/day and 5-FU at 1750 mg/m2/day was administered as either a constant rate or as a circadian infusion over 72 h. During constant rate infusions, 5-FU concentrations within individuals varied by 1.7-fold, but no uniform time of peak or trough concentration was observed. Transformation of these data by setting the time of peak to 0 h and by expressing concentrations as the percentage of the 24-h mean value revealed a nonrandom distribution of the time from peak to trough with a median time of 12 h (P = 0.027). These transformed data were also successfully fit to a circadian cosinor function (P < 0.001). During multiple constant rate 5-FU infusions, the intrapatient variability was high; the times of peak 5-FU concentration occurred at the same approximate sampling time 43% of the time, and troughs coincided 17% of the time. No difference in clinical toxicity was observed when matched constant rate and circadian infusions of 5-FU were compared. High inter- and intrapatient variability exists in 5-FU plasma concentrations in adult cancer patients during constant rate infusions with no evidence of a consistent circadian rhythm in untransformed data. JF - Clinical cancer research : an official journal of the American Association for Cancer Research AU - Takimoto, C H AU - Yee, L K AU - Venzon, D J AU - Schuler, B AU - Grollman, F AU - Chabuk, C AU - Hamilton, J M AU - Chen, A P AU - Allegra, C J AU - Grem, J L AD - Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20889, USA. ctakim@helix.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1347 EP - 1352 VL - 5 IS - 6 SN - 1078-0432, 1078-0432 KW - Antimetabolites, Antineoplastic KW - 0 KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Rectal Neoplasms -- drug therapy KW - Rectal Neoplasms -- blood KW - Reproducibility of Results KW - Infusions, Intravenous KW - Pancreatic Neoplasms -- blood KW - Humans KW - Aged KW - Chronotherapy KW - Stomach Neoplasms -- drug therapy KW - Adult KW - Colonic Neoplasms -- drug therapy KW - Stomach Neoplasms -- blood KW - Middle Aged KW - Pancreatic Neoplasms -- drug therapy KW - Time Factors KW - Colonic Neoplasms -- blood KW - Female KW - Male KW - Fluorouracil -- administration & dosage KW - Fluorouracil -- adverse effects KW - Antimetabolites, Antineoplastic -- administration & dosage KW - Digestive System Neoplasms -- drug therapy KW - Antimetabolites, Antineoplastic -- adverse effects KW - Antimetabolites, Antineoplastic -- blood KW - Antimetabolites, Antineoplastic -- pharmacokinetics KW - Fluorouracil -- pharmacokinetics KW - Fluorouracil -- blood KW - Digestive System Neoplasms -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69860264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=High+inter-+and+intrapatient+variation+in+5-fluorouracil+plasma+concentrations+during+a+prolonged+drug+infusion.&rft.au=Takimoto%2C+C+H%3BYee%2C+L+K%3BVenzon%2C+D+J%3BSchuler%2C+B%3BGrollman%2C+F%3BChabuk%2C+C%3BHamilton%2C+J+M%3BChen%2C+A+P%3BAllegra%2C+C+J%3BGrem%2C+J+L&rft.aulast=Takimoto&rft.aufirst=C&rft.date=1999-06-01&rft.volume=5&rft.issue=6&rft.spage=1347&rft.isbn=&rft.btitle=&rft.title=Clinical+cancer+research+%3A+an+official+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10780432&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetics of alcoholism and substance abuse. AN - 69852407; 10385934 AB - Twin studies have demonstrated that addictive disorders are genetically and environmentally influenced. Our knowledge of behavioral differences predisposing to addiction is advancing rapidly, particularly in alcoholism but also in the other addictions, through studies on animals and humans. Recently, linkage analyses in humans and rodents have pointed to genomic regions harboring genes which influence addiction or drug-associated behaviors. There is increasing evidence that the addictions have common as well as distinct neurobiological pathways. These advances in the understanding of the genetics of addictive disorders should facilitate the development of specific pharmacotherapies and the more accurate targeting of therapies using molecular diagnostic approaches. JF - The Psychiatric clinics of North America AU - Enoch, M A AU - Goldman, D AD - Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA. maenoch@dicbr.niaaa.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 289 EP - 99, viii VL - 22 IS - 2 SN - 0193-953X, 0193-953X KW - Serotonin KW - 333DO1RDJY KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Genetic Linkage KW - Animals KW - Chromosome Aberrations -- genetics KW - Polymorphism, Genetic KW - Humans KW - Chromosome Disorders KW - Ethanol -- metabolism KW - Alcoholism -- genetics KW - Comorbidity KW - Phenotype KW - Alleles KW - Serotonin -- cerebrospinal fluid KW - Adult KW - Alcoholism -- classification KW - Alcoholism -- ethnology KW - Middle Aged KW - Adolescent KW - Behavior, Addictive -- genetics KW - Male KW - Female KW - Substance-Related Disorders -- drug therapy KW - Substance-Related Disorders -- metabolism KW - Substance-Related Disorders -- ethnology KW - Substance-Related Disorders -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69852407?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Psychiatric+clinics+of+North+America&rft.atitle=Genetics+of+alcoholism+and+substance+abuse.&rft.au=Enoch%2C+M+A%3BGoldman%2C+D&rft.aulast=Enoch&rft.aufirst=M&rft.date=1999-06-01&rft.volume=22&rft.issue=2&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=The+Psychiatric+clinics+of+North+America&rft.issn=0193953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-12 N1 - Date created - 1999-08-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. AN - 69827322; 10372688 AB - Multidrug antiretroviral regimens that include human immunodeficiency virus-1 (HIV-1) protease inhibitors are associated with distinct lipodystrophy, hypertriglyceridemia, hyperinsulinemia, and deposition of visceral abdominal adipose tissue. To determine whether these findings are related to abnormalities of adrenal function, we compared the hypothalamic-pituitary-adrenal axes of HIV-positive patients who had evidence of protease inhibitor-associated lipodystrophy (PIAL), control volunteers (CON), and patients with Cushing's syndrome (CS). To elucidate the metabolic consequences of the observed lipodystrophy, we measured basal serum lipids and compared glucose and insulin concentrations during an oral glucose tolerance test. Spontaneous plasma cortisol showed normal diurnal variation in PIAL. Cortisol levels were similar in CON and PIAL, and levels in these groups were less than those in CS at all times of the night or day (P < 0.005). Ovine CRH-stimulated morning plasma cortisol levels were similar in PIAL and CON. ACTH was significantly greater in PIAL than CON (P < 0.05) at 0, 15, and 30 min after CRH stimulation. Urinary free cortisol in PIAL (mean +/- SD, 76 +/- 51 nmol/day) was significant lower than those in CON (165 +/- 64 nmol/day; P < 0.001) and CS (1715 +/- 1203 nmol/day; P < 0.001). However, 17-hydroxycorticosteroid excretion was significantly greater in PIAL (43 +/- 23 micromol/day) than in CON (17 +/- 8 micromol/day; P < 0.001), although lower than that in CS (74 +/- 47 micromol/day; P < 0.01). Scatchard analysis revealed normal glucocorticoid receptor number and affinity in PIAL. Serum triglycerides were significantly greater in PIAL (6.57 +/- 5.63 mmol/L) than in CS (1.78 +/- 0.83 mmol/L; P < 0.001) or CON (1.36 +/- 0.84 mmol/L; P < 0.001). Although triglyceride levels were significantly correlated with body mass index for CON and CS, these were not correlated for PIAL. During an oral glucose tolerance test, similar glucose and insulin values were found in PIAL and CS that were greater (P < 0.05) than CON values at 30, 60, 90, and 120 min. We conclude that the lipodystrophy associated with use of HIV-1 protease inhibitors is a syndrome of increased intraabdominal adiposity with concomitant dyslipidemia and insulin resistance, but without total body weight gain and is distinct from any known form of hypercortisolism. Although urinary cortisol disposition seems to be altered in HIV-infected patients who are being treated with multidrug regimens that include protease inhibitors, the decreased free cortisol and increased 17-hydroxycorticosteroid excretion appear to be unlikely explanations for the observed lipodystrophy. The cause remains to be elucidated. JF - The Journal of clinical endocrinology and metabolism AU - Yanovski, J A AU - Miller, K D AU - Kino, T AU - Friedman, T C AU - Chrousos, G P AU - Tsigos, C AU - Falloon, J AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. jy15i@nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1925 EP - 1931 VL - 84 IS - 6 SN - 0021-972X, 0021-972X KW - HIV Protease Inhibitors KW - 0 KW - Hormones KW - Insulin KW - Lipids KW - Receptors, Glucocorticoid KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Transcortin KW - 9010-38-2 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Lipids -- blood KW - Glucose Tolerance Test KW - Humans KW - Insulin -- blood KW - Body Mass Index KW - Receptors, Glucocorticoid -- metabolism KW - Hydrocortisone -- blood KW - Adult KW - Hydrocortisone -- urine KW - Middle Aged KW - Transcortin -- metabolism KW - Female KW - Male KW - Adrenocorticotropic Hormone -- blood KW - HIV Infections -- blood KW - Lipodystrophy -- metabolism KW - HIV Infections -- drug therapy KW - Lipodystrophy -- chemically induced KW - Hormones -- blood KW - HIV Infections -- metabolism KW - Endocrine System -- drug effects KW - HIV Protease Inhibitors -- therapeutic use KW - HIV Protease Inhibitors -- adverse effects KW - HIV-1 KW - Endocrine System -- metabolism KW - Lipodystrophy -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69827322?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Endocrine+and+metabolic+evaluation+of+human+immunodeficiency+virus-infected+patients+with+evidence+of+protease+inhibitor-associated+lipodystrophy.&rft.au=Yanovski%2C+J+A%3BMiller%2C+K+D%3BKino%2C+T%3BFriedman%2C+T+C%3BChrousos%2C+G+P%3BTsigos%2C+C%3BFalloon%2C+J&rft.aulast=Yanovski&rft.aufirst=J&rft.date=1999-06-01&rft.volume=84&rft.issue=6&rft.spage=1925&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-02 N1 - Date created - 1999-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Acceleration of c-myc-induced hepatocarcinogenesis by Co-expression of transforming growth factor (TGF)-alpha in transgenic mice is associated with TGF-beta1 signaling disruption. AN - 69816403; 10362794 AB - We have previously shown in transgenic mice that transforming growth factor (TGF)-alpha dramatically enhances c-myc-induced hepatocarcinogenesis by promoting proliferation and survival of hepatocellular carcinoma (HCC) cells. As transgenic livers display increased levels of mature TGF-beta1 from the early stages of hepatocarcinogenesis, we have now assessed whether impairment of TGF-beta1 signaling contributes to the deregulation of cell cycle progression and apoptosis observed during this process. Focal preneoplastic lesions lacking expression of TGF-beta receptor type II (TbetaRII) were detected in c-myc/TGF-alpha but not in c-myc livers. In c-myc/TGF-alpha mice, 40% (2/5) of adenomas and 90% (27/30) of HCCs showed down-regulation of TbetaRII expression in comparison with 11% (2/18) of adenomas and 47% (14/30) of HCCs in c-myc mice. Down-regulation of the TGF-beta1-inducible p15(INK4B) mRNA and reduced apoptotic rates in TbetaRII-negative HCCs further indicated the disruption of TGF-beta1 signaling. Furthermore, both TbetaRII-negative and -positive c-myc TGF-alpha HCCs, but not c-myc HCCs, were characterized by decreased levels of the cell cycle inhibitor p27. These results suggest 1) an inverse correlation of decreased p27 expression with the particularly strong expression of TGF-alpha in these lesions, consistent with the capacity of TGF-alpha signaling to post-transcriptionally regulate p27, and 2) the presence of alternative, downstream defects of TGF-beta1 signaling in c-myc/TGF-alpha HCCs that may impair the growth-inhibitory response to TGF-beta1. Thus, the accelerated neoplastic development in c-myc/TGF-alpha mice is associated with an early and frequent occurrence of TbetaRII-negative lesions and with reduced levels of p27 in HCC cells, indicating that disruption of TGF-beta1 responsiveness may play a crucial role in the enhancement of c-myc-induced hepatocarcinogenesis by TGF-alpha. JF - The American journal of pathology AU - Santoni-Rugiu, E AU - Jensen, M R AU - Factor, V M AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1693 EP - 1700 VL - 154 IS - 6 SN - 0002-9440, 0002-9440 KW - Carrier Proteins KW - 0 KW - Cdkn1b protein, mouse KW - Cdkn2b protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p15 KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Enzyme Inhibitors KW - Microtubule-Associated Proteins KW - Proto-Oncogene Proteins c-myc KW - RNA, Messenger KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor alpha KW - Transforming Growth Factor beta KW - Tumor Suppressor Proteins KW - Cyclin-Dependent Kinase Inhibitor p27 KW - 147604-94-2 KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Microtubule-Associated Proteins -- metabolism KW - Blotting, Northern KW - Carrier Proteins -- metabolism KW - Receptors, Transforming Growth Factor beta -- metabolism KW - Mice KW - Mice, Transgenic KW - RNA, Messenger -- biosynthesis KW - Blotting, Western KW - Down-Regulation KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Enzyme Inhibitors -- metabolism KW - Immunohistochemistry KW - Male KW - Liver Neoplasms, Experimental -- genetics KW - Liver Neoplasms, Experimental -- metabolism KW - Proto-Oncogene Proteins c-myc -- physiology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Proto-Oncogene Proteins c-myc -- biosynthesis KW - Carcinoma, Hepatocellular -- metabolism KW - Transforming Growth Factor alpha -- genetics KW - Transforming Growth Factor alpha -- physiology KW - Carcinoma, Hepatocellular -- genetics KW - Signal Transduction -- genetics KW - Transforming Growth Factor alpha -- biosynthesis KW - Transforming Growth Factor beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69816403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Acceleration+of+c-myc-induced+hepatocarcinogenesis+by+Co-expression+of+transforming+growth+factor+%28TGF%29-alpha+in+transgenic+mice+is+associated+with+TGF-beta1+signaling+disruption.&rft.au=Santoni-Rugiu%2C+E%3BJensen%2C+M+R%3BFactor%2C+V+M%3BThorgeirsson%2C+S+S&rft.aulast=Santoni-Rugiu&rft.aufirst=E&rft.date=1999-06-01&rft.volume=154&rft.issue=6&rft.spage=1693&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cancer Res. 1998 Jan 1;58(1):123-34 [9426068] Clin Cancer Res. 1997 Jul;3(7):1059-66 [9815784] Cancer Res. 1990 Dec 1;50(23):7581-6 [1701348] Cancer Res. 1993 Apr 15;53(8):1719-23 [8467484] Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5359-63 [8389483] Genes Dev. 1994 Jan;8(1):9-22 [8288131] Mol Cell Biol. 1994 Jun;14(6):3683-94 [8196612] Cell. 1994 Jul 15;78(1):59-66 [8033212] Nature. 1994 Sep 15;371(6494):257-61 [8078588] Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11576-80 [7972105] Oncogene. 1995 Jan 5;10(1):177-84 [7824270] Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):483-7 [7831315] Hepatology. 1995 Mar;21(3):760-6 [7875675] Cancer Res. 1995 Apr 1;55(7):1452-7 [7882352] Science. 1995 Jun 2;268(5215):1336-8 [7761852] Science. 1995 Aug 4;269(5224):682-5 [7624798] Genes Dev. 1995 Aug 1;9(15):1831-45 [7649471] Oncogene. 1995 Aug 17;11(4):635-45 [7651726] FASEB J. 1995 Dec;9(15):1527-36 [8529831] Cell. 1996 May 31;85(5):707-20 [8646779] Am J Pathol. 1996 Aug;149(2):407-28 [8701981] Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9577-82 [8790372] EMBO J. 1996 Dec 2;15(23):6595-604 [8978686] Nat Med. 1997 Feb;3(2):227-30 [9018244] Science. 1996 Mar 29;271(5257):1861-4 [8596954] Nat Med. 1997 Feb;3(2):231-4 [9018245] Carcinogenesis. 1997 Jan;18(1):59-81 [9054591] Cancer Res. 1997 Jun 1;57(11):2089-95 [9187100] Cancer Res. 1997 Jul 1;57(13):2543-6 [9205049] Cancer Res. 1997 Jul 15;57(14):2856-9 [9230189] Cell Growth Differ. 1997 Aug;8(8):921-6 [9269901] Cancer Res. 1997 Aug 15;57(16):3381-5 [9270000] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10351-5 [9294214] Biochem Biophys Res Commun. 1997 Sep 18;238(2):539-43 [9299547] Nature. 1997 Dec 4;390(6659):465-71 [9393997] Cancer Res. 1997 Dec 15;57(24):5441-5 [9407946] Cancer Res. 1997 Dec 15;57(24):5564-70 [9407968] Oncogene. 1997 Dec 11;15(24):2991-7 [9416843] Curr Opin Genet Dev. 1998 Feb;8(1):43-8 [9529604] Oncogene. 1998 Apr 23;16(16):2141-50 [9572495] Oncogene. 1998 May 28;16(21):2797-802 [9652747] Oncogene. 1998 Jul 9;17(1):25-34 [9671311] Cancer Res. 1998 Jul 15;58(14):3101-4 [9679977] J Cell Biol. 1998 Jul 27;142(2):557-71 [9679152] Nat Genet. 1998 Aug;19(4):371-4 [9697699] Annu Rev Biochem. 1998;67:753-91 [9759503] Clin Cancer Res. 1996 Aug;2(8):1255-61 [9816295] Nature. 1998 Nov 12;396(6707):177-80 [9823898] Cell. 1990 Jul 13;62(1):175-85 [2163767] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model. AN - 69815195; 10368091 AB - A traditional approach to achieve greater analgesic efficacy is to combine an efficacious dose of a nonopioid with a dose of an opioid sufficient to produce additive analgesia without a substantial increase in the incidence of adverse effects. This study evaluated the additive analagesic effects of the combination of ibuprofen and oxycodone. A dose of 400 mg ibuprofen was compared with 400 mg ibuprofen with oxycodone in doses of 2.5, 5, or 10 mg in the oral surgery model of acute pain. Analgesic efficacy was measured with category and visual analog scales at 15, 30, 45, and 60 minutes and hourly up to 6 hours. Ibuprofen plus 10 mg oxycodone produced significantly greater analgesia compared with the other three groups, as measured by the visual analog scale from 15 minutes after drug administration up to the 2-hour observation. All four treatments were similar from 3 to 6 hours, with the area under the pain intensity difference curve being similar across groups. Neither the 2.5-mg nor the 5-mg oxycodone dose provided any additive analgesia over ibuprofen at any points. Addition of oxycodone resulted in a dose-related increase in the number of patients reporting adverse effects, with significantly greater drowsiness and vomiting at the 10-mg dose. These results indicate that additive analgesia can be achieved for the combination of a nonsteroidal anti-inflammatory drug and an orally effective opioid, with faster onset of relief for the combination of 400 mg ibuprofen and 10 mg oxycodone over the first 2 hours after administration, but at the expense of an increased incidence of adverse events. JF - Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons AU - Dionne, R A AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. dionne@yoda.nidr.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 673 EP - 678 VL - 57 IS - 6 SN - 0278-2391, 0278-2391 KW - Analgesics, Opioid KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Drug Combinations KW - Oxycodone KW - CD35PMG570 KW - Ibuprofen KW - WK2XYI10QM KW - Abridged Index Medicus KW - Dentistry KW - Index Medicus KW - Tooth, Impacted -- surgery KW - Anesthesia, Dental KW - Anesthesia Recovery Period KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Vomiting -- etiology KW - Pain Measurement KW - Tooth Extraction KW - Male KW - Female KW - Molar, Third -- surgery KW - Oxycodone -- adverse effects KW - Pain, Postoperative -- drug therapy KW - Oxycodone -- administration & dosage KW - Ibuprofen -- administration & dosage KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Analgesics, Opioid -- adverse effects KW - Analgesics, Opioid -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69815195?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.atitle=Additive+analgesic+effects+of+oxycodone+and+ibuprofen+in+the+oral+surgery+model.&rft.au=Dionne%2C+R+A&rft.aulast=Dionne&rft.aufirst=R&rft.date=1999-06-01&rft.volume=57&rft.issue=6&rft.spage=673&rft.isbn=&rft.btitle=&rft.title=Journal+of+oral+and+maxillofacial+surgery+%3A+official+journal+of+the+American+Association+of+Oral+and+Maxillofacial+Surgeons&rft.issn=02782391&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-16 N1 - Date created - 1999-06-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - p53-mediated apoptosis is attenuated in Werner syndrome cells. AN - 69814755; 10364153 AB - The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53- mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients. JF - Genes & development AU - Spillare, E A AU - Robles, A I AU - Wang, X W AU - Shen, J C AU - Yu, C E AU - Schellenberg, G D AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 1355 EP - 1360 VL - 13 IS - 11 SN - 0890-9369, 0890-9369 KW - Tumor Suppressor Protein p53 KW - 0 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - RecQ Helicases KW - EC 3.6.4.12 KW - WRN protein, human KW - Werner Syndrome Helicase KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - Humans KW - Mice KW - Fibroblasts -- cytology KW - Fibroblasts -- metabolism KW - Werner Syndrome -- pathology KW - Apoptosis KW - DNA Helicases -- metabolism KW - DNA Helicases -- genetics KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69814755?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes+%26+development&rft.atitle=p53-mediated+apoptosis+is+attenuated+in+Werner+syndrome+cells.&rft.au=Spillare%2C+E+A%3BRobles%2C+A+I%3BWang%2C+X+W%3BShen%2C+J+C%3BYu%2C+C+E%3BSchellenberg%2C+G+D%3BHarris%2C+C+C&rft.aulast=Spillare&rft.aufirst=E&rft.date=1999-06-01&rft.volume=13&rft.issue=11&rft.spage=1355&rft.isbn=&rft.btitle=&rft.title=Genes+%26+development&rft.issn=08909369&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Bioessays. 1993 Jun;15(6):421-6 [8357345] Nature. 1993 Apr 29;362(6423):849-52 [8479523] Cell. 1994 Sep 9;78(5):739-50 [8087842] Nat Genet. 1995 Jun;10(2):188-95 [7663514] Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7 [7568133] Genes Dev. 1996 May 15;10(10):1219-32 [8675009] Cancer Epidemiol Biomarkers Prev. 1996 Apr;5(4):239-46 [8722214] Genetics. 1996 Nov;144(3):935-45 [8913739] Cancer Surv. 1996;28:169-96 [8977035] Am J Hum Genet. 1997 Feb;60(2):330-41 [9012406] Cell. 1997 Feb 7;88(3):323-31 [9039259] Hum Genet. 1997 Feb;99(2):191-3 [9048918] Curr Opin Genet Dev. 1997 Jun;7(3):354-63 [9229111] Nat Genet. 1997 Aug;16(4):335-6 [9241267] Nat Genet. 1997 Sep;17(1):100-3 [9288107] Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14707-12 [9405677] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6887-92 [9618508] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8733-8 [9671747] Nat Genet. 1998 Aug;19(4):375-8 [9697700] Nat Genet. 1998 Oct;20(2):114-6 [9771700] Mol Cell Biol. 1998 Nov;18(11):6191-200 [9774636] Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13097-102 [9789047] J Biol Chem. 1998 Dec 18;273(51):34139-44 [9852073] Nature. 1991 Jul 25;352(6333):345-7 [1852210] Medicine (Baltimore). 1966 May;45(3):177-221 [5327241] Science. 1991 Jul 5;253(5015):49-53 [1905840] Nature. 1992 Jul 2;358(6381):15-6 [1614522] Nature. 1993 Apr 29;362(6423):847-9 [8479522] Cell. 1994 Aug 26;78(4):703-11 [8069917] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A standardized protocol for assessing regulators of pigmentation. AN - 69809559; 10334838 AB - Varied effects of chemical or biological compounds on mammalian pigmentation have been reported by many groups, but to date, no standardized method has established necessary and/or optimal parameters for testing such agents. A standardized method has been developed to screen compounds with potential effects on pigmentation. The protocol comprises basic parameters to analyze melanogenic effects and allows for further characterization of candidate compounds, providing important insights into their mechanism of action. In this protocol (termed STOPR, for standardized testing of pigmentation regulators), compounds are initially screened using purified tyrosinase and are then tested on melanocytes in culture. After treatment of melanocytes with potentially bioactive compounds, cell proliferation and viability, total melanin accumulated, and melanogenic potential are measured. This protocol is an important first step in characterizing chemical regulation of effects on melanogenesis. When bioactive candidate compounds are identified, testing may proceed for pharmacological or otherwise commercial applications in coculture and/or organ culture models followed by in vivo testing. As an application of this method, results for compounds known to stimulate and/or inhibit melanogenesis (including arbutin, hydroquinone, kojic acid, melanocyte-stimulating hormone, and thymidine dimers) as well as some commercial skin whiteners are reported. JF - Analytical biochemistry AU - Virador, V M AU - Kobayashi, N AU - Matsunaga, J AU - Hearing, V J AD - Laboratory of Cell Biology, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 207 EP - 219 VL - 270 IS - 2 SN - 0003-2697, 0003-2697 KW - Enzyme Inhibitors KW - 0 KW - Hydroquinones KW - Melanins KW - Pyrimidine Dimers KW - Pyrones KW - Niacinamide KW - 25X51I8RD4 KW - kojic acid KW - 6K23F1TT52 KW - Melanocyte-Stimulating Hormones KW - 9002-79-3 KW - Arbutin KW - C5INA23HXF KW - Monophenol Monooxygenase KW - EC 1.14.18.1 KW - hydroquinone KW - XV74C1N1AE KW - Index Medicus KW - Monophenol Monooxygenase -- metabolism KW - Animals KW - Arbutin -- pharmacology KW - Drug Evaluation, Preclinical -- standards KW - Melanocytes -- metabolism KW - Melanocytes -- drug effects KW - Cell Division -- drug effects KW - Mice KW - Melanocytes -- cytology KW - Melanocyte-Stimulating Hormones -- pharmacology KW - Pyrones -- pharmacology KW - Hydroquinones -- pharmacology KW - Melanins -- biosynthesis KW - Pyrimidine Dimers -- pharmacology KW - Niacinamide -- pharmacology KW - Cell Survival -- drug effects KW - Enzyme Activation -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Monophenol Monooxygenase -- antagonists & inhibitors KW - Drug Evaluation, Preclinical -- methods KW - Cell Line KW - Skin Pigmentation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69809559?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+biochemistry&rft.atitle=A+standardized+protocol+for+assessing+regulators+of+pigmentation.&rft.au=Virador%2C+V+M%3BKobayashi%2C+N%3BMatsunaga%2C+J%3BHearing%2C+V+J&rft.aulast=Virador&rft.aufirst=V&rft.date=1999-06-01&rft.volume=270&rft.issue=2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Analytical+biochemistry&rft.issn=00032697&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. AN - 69807238; 10363972 AB - Hereditary genetic defects in DNA repair lead to increased risk of cancer. Polymorphisms in several DNA repair genes have been identified; however, the impact on repair phenotype has not been elucidated. We explored the relationship between polymorphisms in the DNA repair enzyme, XRCC1 (codons 194, 280, and 399), and genotoxic end points measured in two populations: (a) placental aflatoxin B1 DNA (AFB1-DNA) adducts in a group of Taiwanese maternity subjects (n = 120); and (b) somatic glycophorin A (GPA) variants in erythrocytes from a group of North Carolina smokers and nonsmokers (n = 59). AFB1-DNA adducts were measured by ELISA, and erythrocyte GPA variant frequency (NN and NO) was assessed in MN heterozygotes with a flow cytometric assay. XRCC1 genotypes were identified by PCR-RFLPs. The XRCC1 399Gln allele was significantly associated with higher levels of both AFB1-DNA adducts and GPA NN mutations. Individuals with the 399Gln allele were at risk for detectable adducts (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.03). GPA NN variant frequency was significantly higher in 399Gln homozygotes (19.6 x 10(-6)) than in Gln/Arg heterozygotes (11.4 x 10(-6); P < 0.05) or Arg/Arg homozygotes (10.1 x 10(-6); P = 0.01). No significant effects were observed for other XRCC1 polymorphisms. These results suggest that the Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in deficient DNA repair. JF - Cancer research AU - Lunn, R M AU - Langlois, R G AU - Hsieh, L L AU - Thompson, C L AU - Bell, D A AD - Laboratory of Computational Biology and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 2557 EP - 2561 VL - 59 IS - 11 SN - 0008-5472, 0008-5472 KW - DNA Adducts KW - 0 KW - DNA-Binding Proteins KW - Genetic Markers KW - Glycophorin KW - Proteins KW - X-ray repair cross complementing protein 1 KW - aflatoxin B1-DNA adduct KW - Aflatoxin B1 KW - 9N2N2Y55MH KW - Index Medicus KW - Genotype KW - Humans KW - Proteins -- genetics KW - Male KW - Female KW - DNA Adducts -- blood KW - Glycophorin -- genetics KW - DNA Repair KW - Polymorphism, Genetic KW - DNA Damage KW - DNA-Binding Proteins -- genetics KW - Aflatoxin B1 -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807238?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=XRCC1+polymorphisms%3A+effects+on+aflatoxin+B1-DNA+adducts+and+glycophorin+A+variant+frequency.&rft.au=Lunn%2C+R+M%3BLanglois%2C+R+G%3BHsieh%2C+L+L%3BThompson%2C+C+L%3BBell%2C+D+A&rft.aulast=Lunn&rft.aufirst=R&rft.date=1999-06-01&rft.volume=59&rft.issue=11&rft.spage=2557&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Comparison of the polymorphic regions of the cytochrome P450 CYP2E1 gene of humans and patas and cynomolgus monkeys. AN - 69807100; 10357784 AB - Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight toxicants. CYP2E1 gene polymorphisms have been linked to risk of various cancers and liver disease in humans. Since the patas monkey is a promising model for study of cancer-related alcohol/nitrosamine interactions, we examined CYP2E1 in this monkey for characteristics of two regions that are polymorphic in humans, an RsaI site in the 5' promoter region and a DraI site in intron 6. Another monkey species often used in biomedical research, the cynomolgus monkey, was also examined. Human DNA primers used to amplify a 413 bp segment around the RsaI site also amplified a segment of similar size (409 bp) from DNA of 25 patas monkeys, whereas a product of approximately 800 bp was amplified from DNA of eight cynomolgus monkeys. RsaI did not cut the amplified DNA product from either monkey species. Sequencing revealed that the patas RsaI site was identical to that in humans with the c2c2 CYP2E1 genotype, GTAT. The equivalent cynomolgus sequence, CTAC, has not been observed in humans. Thus, the patas monkey appears to be a useful model for CYP2E1 c2c2 humans, and this genotype, present in 2-25% of humans, may be more primitive than c1c1. For the DraI site, the human primers amplified DNA products similar in size to those from humans, from all patas and cynomolgus monkey DNA samples; none were cut by DraI. Thus, both monkey species appeared to be generally similar to humans of CYP2E1 CC DraI genotype, which is the rarer form of the gene. JF - Carcinogenesis AU - Chhabra, S K AU - Reed, C D AU - Anderson, L M AU - Shiao, Y H AD - Laboratory of Comparative Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1031 EP - 1034 VL - 20 IS - 6 SN - 0143-3334, 0143-3334 KW - DNA KW - 9007-49-2 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Index Medicus KW - Animals KW - Promoter Regions, Genetic KW - Base Sequence KW - Macaca fascicularis KW - Sequence Homology, Nucleic Acid KW - Humans KW - Erythrocebus KW - Molecular Sequence Data KW - Species Specificity KW - Polymorphism, Genetic KW - Cytochrome P-450 CYP2E1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Comparison+of+the+polymorphic+regions+of+the+cytochrome+P450+CYP2E1+gene+of+humans+and+patas+and+cynomolgus+monkeys.&rft.au=Chhabra%2C+S+K%3BReed%2C+C+D%3BAnderson%2C+L+M%3BShiao%2C+Y+H&rft.aulast=Chhabra&rft.aufirst=S&rft.date=1999-06-01&rft.volume=20&rft.issue=6&rft.spage=1031&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-22 N1 - Date created - 1999-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo mutagenicity and hepatocarcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in bitransgenic c-myc/lambda lacZ mice. AN - 69807072; 10363978 AB - 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a mutagenic and carcinogenic heterocyclic amine found in cooked meat. Hepatic DNA adduct formation, in vivo mutagenicity, and hepatocarcinogenicity of MeIQx were examined in mice harboring the lacZ mutation reporter gene (Muta mice) and bitransgenic mice overexpressing the c-myc oncogene. C57Bl/lambda lacZ and bitransgenic c-myc (albumin promoter)/lambda lacZ mice were bred and weaned onto an American Institute of Nutrition-76-based diet containing 0.06% (w/w) MeIQx or onto control diet. After 30 weeks on diet, only male bitransgenic mice on MeIQx developed hepatocellular carcinoma (100% incidence). By 40 weeks, hepatic tumor incidence was 100%/75% (17%/0%) and 44%/17% (0%/0%) in male c-myc/lambda lacZ and C57Bl/lambda lacZ mice who were given MeIQx (or control) diet, respectively, supporting a synergism between MeIQx and c-myc overexpression in hepatocarcinogenesis. At either time point, mutant frequency in the lacZ gene was at least 40-fold higher in MeIQx-treated mice than in control mice of either strain. These findings suggest that MeIQx-induced hepatocarcinogenesis is associated with MeIQx-induced mutations. Elevated mutant frequency in MeIQx-treated mice also occurred concomitant with the formation of MeIQx-guanine adducts, as detected by the 32P-postlabeling assay. Irrespective of strain or diet, sequence analysis of the lacZ mutants from male mouse liver showed that the principal sequence alterations were base substitutions at guanine bases. Adenine mutations, however, were detected only in animals on control diet. MeIQx-fed mice harboring the c-myc oncogene showed a 1.4-2.6-fold higher mutant frequency in the lacZ gene than mice not carrying the transgene. Although there was a trend toward higher adduct levels in c-myc mice, MeIQx-DNA adduct levels were not significantly different between c-myc/lambda lacZ and C57Bl/lambda lacZ mice after 30 weeks on diet. Thus, it seemed that factors in addition to MeIQx-DNA adduct levels, such as the enhanced rate of proliferation associated with c-myc overexpression, may have accounted for a higher mutant frequency in c-myc mice. In the control diet groups, the lacZ mutant frequency was significantly higher in c-myc/lambda lacZ mice than in C57Bl/lambda lacZ mice. The findings are consistent with the notion that c-myc overexpression is associated with an increase in mutagenesis. The mechanism for the synergistic effects of c-myc overexpression on MeIQx hepatocarcinogenicity seems to involve an enhanced expression of MeIQx-induced mutations. JF - Cancer research AU - Ryu, D Y AU - Pratt, V S AU - Davis, C D AU - Schut, H A AU - Snyderwine, E G AD - Chemical Carcinogenesis Section, Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 2587 EP - 2592 VL - 59 IS - 11 SN - 0008-5472, 0008-5472 KW - Carcinogens KW - 0 KW - DNA Adducts KW - Mutagens KW - Quinoxalines KW - 3,4,8-trimethylimidazo(4,5-f)quinoxalin-2-amine KW - YRA7G7WU6P KW - Index Medicus KW - Animals KW - Mice, Inbred CBA KW - Sex Factors KW - Liver Neoplasms, Experimental -- chemically induced KW - Mice KW - Sequence Analysis, DNA KW - Mice, Transgenic KW - Mice, Inbred BALB C KW - Lac Operon KW - Male KW - Female KW - Mice, Inbred DBA KW - DNA Adducts -- toxicity KW - Carcinogens -- metabolism KW - Mutagens -- metabolism KW - Quinoxalines -- toxicity KW - Quinoxalines -- metabolism KW - Carcinogens -- toxicity KW - Mutagens -- toxicity KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69807072?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=In+vivo+mutagenicity+and+hepatocarcinogenicity+of+2-amino-3%2C8-dimethylimidazo%5B4%2C5-f%5Dquinoxaline+%28MeIQx%29+in+bitransgenic+c-myc%2Flambda+lacZ+mice.&rft.au=Ryu%2C+D+Y%3BPratt%2C+V+S%3BDavis%2C+C+D%3BSchut%2C+H+A%3BSnyderwine%2C+E+G&rft.aulast=Ryu&rft.aufirst=D&rft.date=1999-06-01&rft.volume=59&rft.issue=11&rft.spage=2587&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Retinoic acid and 4-hydroxyphenylretinamide induce growth inhibition and tissue transglutaminase through different signal transduction pathways in mouse fibroblasts (NIH 3T3 cells). AN - 69806876; 10357800 AB - 4-Hydroxyphenylretinamide (4-HPR) is a synthetic retinoid with minimal toxicity and favorable pharmacokinetics during long-term administration to patients in clinical trials. Since 4-HPR binds poorly to the retinoic acid receptors, the issue of whether 4-HPR exerts its biological actions via classical retinoid receptor pathways remains to be resolved. We have previously reported that stable expression of a truncated retinoic acid receptor alpha, RARalpha403, transduced in NIH 3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and induction of tissue transglutaminase (TGase II). Here, we report that stable expression of the dominant negative construct RARalpha403 fails to blunt growth inhibition and TGase II induction by 4-HPR, a potent chemopreventive retinoid, in the same cells. These data show that retinoic acid receptors do not mediate either growth inhibition or induction of TGase II activity by 4-HPR in mouse fibroblast cells. JF - Carcinogenesis AU - Giandomenico, V AU - Andreola, F AU - Rodriguez de la Concepcion, M L AU - Collins, S J AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1133 EP - 1135 VL - 20 IS - 6 SN - 0143-3334, 0143-3334 KW - Fenretinide KW - 187EJ7QEXL KW - Tretinoin KW - 5688UTC01R KW - transglutaminase 2 KW - EC 2.3.2.- KW - Transglutaminases KW - EC 2.3.2.13 KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Proteins KW - Index Medicus KW - Fibroblasts -- drug effects KW - Animals KW - 3T3 Cells KW - Fibroblasts -- enzymology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Mice KW - Fibroblasts -- metabolism KW - Tretinoin -- pharmacology KW - GTP Phosphohydrolases -- genetics KW - Fenretinide -- pharmacology KW - Transglutaminases -- genetics KW - Cell Division -- drug effects KW - Transglutaminases -- biosynthesis KW - Signal Transduction KW - GTP Phosphohydrolases -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69806876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Retinoic+acid+and+4-hydroxyphenylretinamide+induce+growth+inhibition+and+tissue+transglutaminase+through+different+signal+transduction+pathways+in+mouse+fibroblasts+%28NIH+3T3+cells%29.&rft.au=Giandomenico%2C+V%3BAndreola%2C+F%3BRodriguez+de+la+Concepcion%2C+M+L%3BCollins%2C+S+J%3BDe+Luca%2C+L+M&rft.aulast=Giandomenico&rft.aufirst=V&rft.date=1999-06-01&rft.volume=20&rft.issue=6&rft.spage=1133&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-22 N1 - Date created - 1999-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - DNA polymerase beta expression differences in selected human tumors and cell lines. AN - 69806557; 10357787 AB - A long-standing question in cancer biology has been the extent to which DNA repair may be altered during the process of carcinogenesis. We have shown recently that DNA polymerase beta (beta-pol) provides a rate-determining function during in vitro repair of abasic sites by one of the mammalian DNA base excision repair pathways. Therefore, altered expression of beta-pol during carcinogenesis could alter base excision repair and, consequently, be critical to the integrity of the mammalian genome. We examined the expression of beta-pol in several cell lines and human adenocarcinomas using a quantitative immunoblotting method. In cell lines from normal breast or colon, the level of beta-pol was approximately 1 ng/mg cell extract, whereas in all of the breast and colon adenocarcinoma cell lines tested, a higher level of beta-pol was observed. In tissue samples, colon adenocarcinomas had a higher level of beta-pol than adjacent normal mucosa. Breast adenocarcinomas exhibited a wide range of beta-pol expression: one tumor had a much higher level of beta-pol (286 ng/mg cell extract) than adjacent normal breast tissue, whereas another tumor had the same level of beta-pol as adjacent normal tissue. Differences in beta-pol expression level, from normal to elevated, were also observed with prostate adenocarcinomas. All kidney adenocarcinomas tested had a slightly lower beta-pol level than adjacent normal tissue. This study reveals that the base excision repair enzyme DNA polymerase beta is up-regulated in some types of adenocarcinomas and cell lines, but not in others. JF - Carcinogenesis AU - Srivastava, D K AU - Husain, I AU - Arteaga, C L AU - Wilson, S H AD - Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Department of Functional Genetics, GlaxoWellcome Inc., Five Moore Drive, Research Triangle Park, NC 27709, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1049 EP - 1054 VL - 20 IS - 6 SN - 0143-3334, 0143-3334 KW - Antibodies, Monoclonal KW - 0 KW - Epitopes KW - DNA Polymerase beta KW - EC 2.7.7.- KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Antibodies, Monoclonal -- immunology KW - Colonic Neoplasms -- enzymology KW - Adenocarcinoma -- enzymology KW - Blotting, Western KW - Tumor Cells, Cultured KW - Molecular Sequence Data KW - CHO Cells KW - Middle Aged KW - Epitopes -- chemistry KW - Breast Neoplasms -- enzymology KW - Cell Line KW - Female KW - Cricetinae KW - DNA Polymerase beta -- immunology KW - DNA Polymerase beta -- chemistry KW - DNA Polymerase beta -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69806557?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=DNA+polymerase+beta+expression+differences+in+selected+human+tumors+and+cell+lines.&rft.au=Srivastava%2C+D+K%3BHusain%2C+I%3BArteaga%2C+C+L%3BWilson%2C+S+H&rft.aulast=Srivastava&rft.aufirst=D&rft.date=1999-06-01&rft.volume=20&rft.issue=6&rft.spage=1049&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-22 N1 - Date created - 1999-07-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Beta-carotene and lung cancer: a case study. AN - 69801131; 10359235 AB - The conflicting evidence of the relation between beta-carotene and lung cancer in humans serves as a poignant case study with respect to what types of evidence are sufficient to support or change a nutrition recommendation. This article is a review of the available evidence of the relation between beta-carotene and lung cancer, including data regarding beta-carotene intake (from diet and supplements), beta-carotene biochemical status, and vegetable and fruit consumption, and a discussion of the role of this evidence in making nutrition recommendations. More than 30 case-control and cohort studies were conducted over many years in various populations and indicated that people who eat more vegetables and fruit, foods rich in carotenoids, and carotenoids (beta-carotene in particular), as well as those with higher blood beta-carotene concentrations, have a lower risk of lung cancer than those who eat fewer such foods or have lower beta-carotene concentrations. In contrast, the intervention results from large, controlled trials of beta-carotene supplementation do not support the observed beneficial associations or a role for supplemental beta-carotene in lung cancer prevention; instead, they provide striking evidence for adverse effects (ie, excess lung cancer incidence and overall mortality) in smokers. The findings require that caution be exercised in recommending supplemental beta-carotene, particularly for smokers, and argue against changing the vegetable-fruit recommendations in the direction of greater nutrient specificity. This case study of beta-carotene and lung cancer stresses the importance of having results from at least one, and preferably more, large, randomized intervention trial before public health recommendations concerning micronutrient supplementation are considered. JF - The American journal of clinical nutrition AU - Albanes, D AD - Cancer Prevention Studies Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892-7058, USA. daa@nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1345S EP - 1350S VL - 69 IS - 6 SN - 0002-9165, 0002-9165 KW - Antioxidants KW - 0 KW - beta Carotene KW - 01YAE03M7J KW - Abridged Index Medicus KW - Index Medicus KW - Vegetables KW - Randomized Controlled Trials as Topic KW - Epidemiologic Studies KW - Humans KW - Nutrition Policy KW - Fruit KW - beta Carotene -- administration & dosage KW - Antioxidants -- adverse effects KW - Lung Neoplasms -- prevention & control KW - beta Carotene -- therapeutic use KW - Antioxidants -- therapeutic use KW - beta Carotene -- adverse effects KW - Diet KW - Antioxidants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69801131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+clinical+nutrition&rft.atitle=Beta-carotene+and+lung+cancer%3A+a+case+study.&rft.au=Albanes%2C+D&rft.aulast=Albanes&rft.aufirst=D&rft.date=1999-06-01&rft.volume=69&rft.issue=6&rft.spage=1345S&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+clinical+nutrition&rft.issn=00029165&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-24 N1 - Date created - 1999-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Vanilloid (Capsaicin) receptors and mechanisms. AN - 69800622; 10353985 JF - Pharmacological reviews AU - Szallasi, A AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, USA. arpads@thalamus.wustl.edu Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 159 EP - 212 VL - 51 IS - 2 SN - 0031-6997, 0031-6997 KW - Receptors, Drug KW - 0 KW - Capsaicin KW - S07O44R1ZM KW - Index Medicus KW - Animals KW - Humans KW - Receptors, Drug -- metabolism KW - Receptors, Drug -- drug effects KW - Capsaicin -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69800622?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+reviews&rft.atitle=Vanilloid+%28Capsaicin%29+receptors+and+mechanisms.&rft.au=Szallasi%2C+A%3BBlumberg%2C+P+M&rft.aulast=Szallasi&rft.aufirst=A&rft.date=1999-06-01&rft.volume=51&rft.issue=2&rft.spage=159&rft.isbn=&rft.btitle=&rft.title=Pharmacological+reviews&rft.issn=00316997&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conserved extracellular cysteine pair in the M3 muscarinic acetylcholine receptor is essential for proper receptor cell surface localization but not for G protein coupling. AN - 69792544; 10349850 AB - Most G protein-coupled receptors contain a conserved pair of extracellular cysteine residues that are predicted to form a disulfide bond linking the first and second extracellular loops. Previous studies have shown that this disulfide bond may be critical for ligand binding, receptor activation, and/or proper receptor folding. However, the potential importance of the two conserved cysteine residues for proper receptor cell surface localization has not been investigated systematically. To address this issue, we used the rat M3 muscarinic receptor as a model system. Most studies were carried out with a modified version of this receptor subtype (lacking potential N-glycosylation sites and the central portion of the third intracellular loop) that could be readily detected via western blot analysis. Cys-->Ala mutant receptors were generated, transiently expressed in COS-7 cells, and then examined for their subcellular distribution and functional properties. ELISA and immunofluorescence studies showed that the presence of both conserved cysteine residues (corresponding to C140 and C220 in the rat M3 muscarinic receptor sequence) is required for efficient expression of the M3 muscarinic receptor on the cell surface. On the other hand, these residues were found not to be essential for protein stability (determined via immunoblotting) and receptor-mediated G protein activation (studied in second messenger assays). These results shed new light on the functional role of the two extracellular cysteine residues present in most G protein-coupled receptors. JF - Journal of neurochemistry AU - Zeng, F Y AU - Soldner, A AU - Schöneberg, T AU - Wess, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 2404 EP - 2414 VL - 72 IS - 6 SN - 0022-3042, 0022-3042 KW - Disulfides KW - 0 KW - Phosphatidylinositols KW - Receptor, Muscarinic M3 KW - Receptors, Muscarinic KW - Recombinant Proteins KW - Tritium KW - 10028-17-8 KW - Carbachol KW - 8Y164V895Y KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Cysteine KW - K848JZ4886 KW - Alanine KW - OF5P57N2ZX KW - N-Methylscopolamine KW - VDR09VTQ8U KW - Index Medicus KW - Phosphatidylinositols -- metabolism KW - Animals KW - Protein Structure, Secondary KW - COS Cells KW - Models, Molecular KW - Amino Acid Sequence KW - Radioligand Assay KW - Rats KW - Mutagenesis, Site-Directed KW - Conserved Sequence KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Carbachol -- pharmacology KW - Amino Acid Substitution KW - N-Methylscopolamine -- metabolism KW - Receptors, Muscarinic -- genetics KW - GTP-Binding Proteins -- metabolism KW - Receptors, Muscarinic -- chemistry KW - Cell Membrane -- metabolism KW - Receptors, Muscarinic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69792544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Conserved+extracellular+cysteine+pair+in+the+M3+muscarinic+acetylcholine+receptor+is+essential+for+proper+receptor+cell+surface+localization+but+not+for+G+protein+coupling.&rft.au=Zeng%2C+F+Y%3BSoldner%2C+A%3BSch%C3%B6neberg%2C+T%3BWess%2C+J&rft.aulast=Zeng&rft.aufirst=F&rft.date=1999-06-01&rft.volume=72&rft.issue=6&rft.spage=2404&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-14 N1 - Date created - 1999-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Proteasome activity is required for anthrax lethal toxin to kill macrophages. AN - 69777011; 10338520 AB - Anthrax lethal toxin (LeTx), consisting of protective antigen (PA) and lethal factor (LF), rapidly kills primary mouse macrophages and macrophage-like cell lines such as RAW 264.7. LF is translocated by PA into the cytosol of target cells, where it acts as a metalloprotease to cleave mitogen-activated protein kinase kinase 1 (MEK1) and possibly other proteins. In this study, we show that proteasome inhibitors such as acetyl-Leu-Leu-norleucinal, MG132, and lactacystin efficiently block LeTx cytotoxicity, whereas other protease inhibitors do not. The inhibitor concentrations that block LF cytotoxicity are similar to those that inhibit the proteasome-dependent IkappaB-alpha degradation induced by lipopolysaccharide. The inhibitors did not interfere with the proteolytic cleavage of MEK1 in LeTx-treated cells, indicating that they do not directly block the proteolytic activity of LF. However, the proteasome inhibitors did prevent ATP depletion, an early effect of LeTx. No overall activation of the proteasome by LeTx was detected, as shown by the cleavage of fluorogenic substrates of the proteasome. All of these results suggest that the proteasome mediates a toxic process initiated by LF in the cell cytosol. This process probably involves degradation of unidentified molecules that are essential for macrophage homeostasis. Moreover, this proteasome-dependent process is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates. JF - Infection and immunity AU - Tang, G AU - Leppla, S H AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 3055 EP - 3060 VL - 67 IS - 6 SN - 0019-9567, 0019-9567 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Cysteine Proteinase Inhibitors KW - Multienzyme Complexes KW - anthrax toxin KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - MAP Kinase Kinase 1 KW - EC 2.7.12.2 KW - Map2k1 protein, mouse KW - Mitogen-Activated Protein Kinase Kinases KW - Cysteine Endopeptidases KW - EC 3.4.22.- KW - Proteasome Endopeptidase Complex KW - EC 3.4.25.1 KW - Index Medicus KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Animals KW - Protein-Serine-Threonine Kinases -- metabolism KW - Dose-Response Relationship, Drug KW - Adenosine Triphosphate -- metabolism KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Cell Line KW - Macrophages -- cytology KW - Multienzyme Complexes -- metabolism KW - Cysteine Endopeptidases -- metabolism KW - Bacterial Toxins -- toxicity KW - Macrophages -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69777011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Proteasome+activity+is+required+for+anthrax+lethal+toxin+to+kill+macrophages.&rft.au=Tang%2C+G%3BLeppla%2C+S+H&rft.aulast=Tang&rft.aufirst=G&rft.date=1999-06-01&rft.volume=67&rft.issue=6&rft.spage=3055&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-28 N1 - Date created - 1999-06-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Mol Microbiol. 1994 Sep;13(6):1093-100 [7854123] Cell. 1994 Sep 9;78(5):761-71 [8087844] Cell. 1995 Apr 21;81(2):149-52 [7736567] EMBO J. 1996 Aug 1;15(15):3835-44 [8670888] EMBO J. 1996 Aug 1;15(15):3845-52 [8670889] Mol Med. 1994 Nov;1(1):7-18 [8790597] Curr Microbiol. 1996 Oct;33(4):224-7 [8824167] Oncogene. 1996 Oct 3;13(7):1531-5 [8875991] Biochem J. 1996 Dec 1;320 ( Pt 2):687-91 [8973585] Science. 1997 Jan 17;275(5298):400-2 [8994040] Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):855-60 [9023346] Nature. 1997 Feb 27;385(6619):833-8 [9039918] Mol Pharmacol. 1997 Mar;51(3):439-47 [9058599] Genes Cells. 1997 Jan;2(1):13-28 [9112437] J Biol Chem. 1997 May 16;272(20):13437-45 [9148969] Mol Biol Rep. 1997 Mar;24(1-2):3-11 [9228274] Cell. 1997 Oct 31;91(3):299-302 [9363938] Curr Top Microbiol Immunol. 1998;225:13-35 [9386326] J Biol Chem. 1998 Mar 13;273(11):6373-9 [9497367] Biochim Biophys Acta. 1991 Mar 4;1073(2):299-308 [1849005] J Biol Chem. 1998 Apr 10;273(15):8545-8 [9535824] Science. 1998 May 1;280(5364):734-7 [9563949] Infect Immun. 1998 May;66(5):2374-8 [9573135] Science. 1998 May 1;280(5364):676 [9599144] J Immunol. 1998 Jul 1;161(1):35-40 [9647204] Science. 1998 Jun 12;280(5370):1671, 1673-4 [9660700] Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11 [9703991] Mol Microbiol. 1998 Jul;29(2):581-91 [9720874] Cell. 1998 Sep 18;94(6):695-8 [9753316] Proc Natl Acad Sci U S A. 1982 May;79(10):3162-6 [6285339] J Biol Chem. 1986 Jun 5;261(16):7123-6 [3711080] EMBO J. 1991 Mar;10(3):555-62 [2001673] Infect Immun. 1991 Oct;59(10):3472-7 [1910002] EMBO J. 1992 Jul;11(7):2433-46 [1321032] Mol Biol Cell. 1992 Nov;3(11):1269-77 [1457831] Biochemistry. 1993 Feb 16;32(6):1563-72 [8431436] Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10198-201 [8234277] Infect Immun. 1994 Jul;62(7):2958-62 [8005682] Science. 1995 Mar 10;267(5203):1485-8 [7878466] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Down-regulation of nitric oxide production by ibuprofen in human volunteers. AN - 69775483; 10336532 AB - Ibuprofen has been shown in vitro to modulate production of nitric oxide (NO), a mediator of sepsis-induced hypotension. We sought to determine whether ibuprofen alters NO production and, thereby, vascular tone, in normal and endotoxin-challenged volunteers. Techniques for detecting NO were validated in 17 subjects infused with sodium nitroprusside, a NO donor. Then, endotoxin (4 ng/kg) or saline (vehicle alone) was administered in a single-blinded, crossover design to 12 other subjects randomized to receive either ibuprofen (2400 mg p.o.) or a placebo. Endotoxin decreased mean arterial pressure (MAP; P =.002) and increased alveolar NO flow rates (P =.04) and urinary excretion of nitrite and nitrate (P =.07). In both endotoxemic and normal subjects, ibuprofen blunted the small fall in MAP associated with bed rest (P =.005) and decreased alveolar NO flow rates (P =.03) and urinary excretion of nitrite and nitrate (P =.02). However, ibuprofen had no effect on the decrease in MAP caused by endotoxin, although it blocked NO production to the point of disrupting the normal relationship between increases in exhaled NO flow rate and decreases in MAP (P =.002). These are the first in vivo data to demonstrate that ibuprofen down-regulates NO in humans. Ibuprofen impaired the NO response to bed rest, producing a small rise in blood pressure. Although ibuprofen also interfered with the ability of endotoxin to induce NO production, it had no effect on the fall in blood pressure, suggesting that the hemodynamic response to endotoxin is not completely dependent on NO under these conditions. JF - The Journal of pharmacology and experimental therapeutics AU - Vandivier, R W AU - Eidsath, A AU - Banks, S M AU - Preas, H L AU - Leighton, S B AU - Godin, P J AU - Suffredini, A F AU - Danner, R L AD - Department of Critical Care Medicine Warren G. Magnusen Clinical Center, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 1398 EP - 1403 VL - 289 IS - 3 SN - 0022-3565, 0022-3565 KW - Endotoxins KW - 0 KW - Nitrates KW - Carbon Dioxide KW - 142M471B3J KW - Nitroprusside KW - 169D1260KM KW - Nitric Oxide KW - 31C4KY9ESH KW - Cyclic GMP KW - H2D2X058MU KW - Ibuprofen KW - WK2XYI10QM KW - Index Medicus KW - Reproducibility of Results KW - Infusions, Intravenous KW - Cyclic GMP -- urine KW - Humans KW - Nitrates -- blood KW - Nitrates -- urine KW - Carbon Dioxide -- analysis KW - Heart Rate -- drug effects KW - Single-Blind Method KW - Adult KW - Cross-Over Studies KW - Blood Pressure -- drug effects KW - Endotoxins -- toxicity KW - Cyclic GMP -- blood KW - Female KW - Male KW - Pulmonary Alveoli -- drug effects KW - Nitroprusside -- pharmacology KW - Nitric Oxide -- biosynthesis KW - Ibuprofen -- pharmacology KW - Nitroprusside -- administration & dosage KW - Pulmonary Alveoli -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69775483?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Down-regulation+of+nitric+oxide+production+by+ibuprofen+in+human+volunteers.&rft.au=Vandivier%2C+R+W%3BEidsath%2C+A%3BBanks%2C+S+M%3BPreas%2C+H+L%3BLeighton%2C+S+B%3BGodin%2C+P+J%3BSuffredini%2C+A+F%3BDanner%2C+R+L&rft.aulast=Vandivier&rft.aufirst=R&rft.date=1999-06-01&rft.volume=289&rft.issue=3&rft.spage=1398&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-15 N1 - Date created - 1999-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations. AN - 69771089; 10338000 AB - Esophageal cancer is the third most prevalent gastrointestinal malignancy in the world. The tumor responds poorly to various therapeutic regimens and the genetic events underlying esophageal carcinogenesis are not well understood. To identify overall chromosomal aberrations in esophageal squamous cell carcinoma, we performed comparative genomic hybridization (CGH). All 17 tumor samples were found to exhibit multiple gains and losses involving different chromosomal regions. The frequency of chromosomal loss associated with this type of tumor was as follows: in 2q (100%), 3p (100%), 13q (100%), Xq (94%), 4 (82%), 5q (82%), 18q (76%), 9p (76%), 6q (70%), 12q (70%), 14q (65%), 11q (59%), and 1p (53%). Interstitial deletions on 1p, 3p, 5q, 6q, 11q, and 12q were detected also. Chromosomal gains were displayed by chromosomes and chromosome areas: 19 (100%), 20q (94%), 22 (94%), 16p (65%), 17 (59%), 12q (59%), 8q (53%), 9q (53%), and 3q (50%). Two sites showing apparent amplification were 11q (70%) and 5p15 (47%). To validate the CGH data, we isolated a BAC clone mapping to 18q12.1. This clone was used as a probe in interphase fluorescence in situ hybridization of tumor touch preparations and allelic loss was clearly revealed. This study represents the first whole-genome analysis in esophageal squamous cell carcinoma for associated chromosomal aberrations that may be involved in either the genesis or progression of this malignancy. JF - Genes, chromosomes & cancer AU - Pack, S D AU - Karkera, J D AU - Zhuang, Z AU - Pak, E D AU - Balan, K V AU - Hwu, P AU - Park, W S AU - Pham, T AU - Ault, D O AU - Glaser, M AU - Liotta, L AU - Detera-Wadleigh, S D AU - Wadleigh, R G AD - Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 160 EP - 168 VL - 25 IS - 2 SN - 1045-2257, 1045-2257 KW - DNA, Neoplasm KW - 0 KW - Index Medicus KW - Humans KW - Chromosome Disorders KW - Chromosome Aberrations KW - DNA, Neoplasm -- analysis KW - Nucleic Acid Hybridization KW - Esophageal Neoplasms -- genetics KW - Carcinoma, Squamous Cell -- genetics KW - DNA Fingerprinting -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69771089?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genes%2C+chromosomes+%26+cancer&rft.atitle=Molecular+cytogenetic+fingerprinting+of+esophageal+squamous+cell+carcinoma+by+comparative+genomic+hybridization+reveals+a+consistent+pattern+of+chromosomal+alterations.&rft.au=Pack%2C+S+D%3BKarkera%2C+J+D%3BZhuang%2C+Z%3BPak%2C+E+D%3BBalan%2C+K+V%3BHwu%2C+P%3BPark%2C+W+S%3BPham%2C+T%3BAult%2C+D+O%3BGlaser%2C+M%3BLiotta%2C+L%3BDetera-Wadleigh%2C+S+D%3BWadleigh%2C+R+G&rft.aulast=Pack&rft.aufirst=S&rft.date=1999-06-01&rft.volume=25&rft.issue=2&rft.spage=160&rft.isbn=&rft.btitle=&rft.title=Genes%2C+chromosomes+%26+cancer&rft.issn=10452257&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-21 N1 - Date created - 1999-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversion of a human immunodeficiency virus type 1 matrix mutation affecting Gag membrane binding, endogenous reverse transcriptase activity, and virus infectivity. AN - 69746503; 10233933 AB - We previously characterized mutations in the human immunodeficiency virus type 1 matrix (MA) protein that displayed reduced infectivity in single-round assays, defects in the stable synthesis of viral DNA in infected cells, and impaired endogenous reverse transcriptase activity. The mutants, which contained substitutions in a highly conserved Leu at MA amino acid 20, also increased binding of Gag to membrane. To elucidate further the role of MA in the virus replication cycle, we have characterized a viral revertant of an amino acid 20 mutant (20LK). The revertant virus, which replicates with essentially wild-type kinetics in H9 cells, contains second-site compensatory changes at MA amino acids 73 (E-->K) and 82 (A-->T), while retaining the original 20LK mutation. Single-cycle infectivity assays, performed with luciferase-expressing viruses, show that the 20LK/73EK/82AT triple mutant displays markedly improved infectivity relative to the original 20LK mutant. The stable synthesis of viral DNA in infected cells is also significantly increased compared with that of 20LK DNA. Furthermore, activity of revertant virions in endogenous reverse transcriptase assays is restored to near-wild-type-levels. Interestingly, although 20LK/73EK/82AT reverses the defects in replication kinetics, postentry events, and endogenous reverse transcriptase activity induced by the 20LK mutation, the reversion does not affect the 20LK-imposed increase in Gag membrane binding. Mutants containing single and double amino acid substitutions were constructed, and their growth kinetics were examined. Only virus containing all three changes (20LK/73EK/82AT) grew with significantly accelerated kinetics; 73EK, 73EK/82AT, and 20LK/82AT mutants displayed pronounced defects in virus particle production. Viral core-like complexes were isolated by sucrose density gradient centrifugation of detergent-treated virions. Intriguingly, the protein composition of wild-type and mutant detergent-resistant complexes differed markedly. In wild-type and 20LK complexes, MA was removed following detergent solubilization of the viral membrane. In contrast, in revertant preparations, the majority of MA cosedimented with the detergent-resistant complex. These results suggest that the 20LK/73EK/82AT mutations induced a significant alteration in MA-MA or MA-core interactions. JF - Journal of virology AU - Kiernan, R E AU - Ono, A AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 4728 EP - 4737 VL - 73 IS - 6 SN - 0022-538X, 0022-538X KW - Detergents KW - 0 KW - Gene Products, gag KW - Protein Precursors KW - Viral Matrix Proteins KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Mutagenesis, Site-Directed KW - Protein Precursors -- metabolism KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Virion -- physiology KW - Detergents -- pharmacology KW - Cell Membrane -- metabolism KW - Structure-Activity Relationship KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- physiology KW - Gene Products, gag -- metabolism KW - Viral Matrix Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69746503?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Reversion+of+a+human+immunodeficiency+virus+type+1+matrix+mutation+affecting+Gag+membrane+binding%2C+endogenous+reverse+transcriptase+activity%2C+and+virus+infectivity.&rft.au=Kiernan%2C+R+E%3BOno%2C+A%3BFreed%2C+E+O&rft.aulast=Kiernan&rft.aufirst=R&rft.date=1999-06-01&rft.volume=73&rft.issue=6&rft.spage=4728&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Mol Biol. 1967 Jun 14;26(2):365-9 [4291934] J Virol. 1996 Dec;70(12):8701-9 [8970997] J Virol. 1986 Aug;59(2):284-91 [3016298] Nature. 1986 Jul 31-Aug 6;322(6078):470-4 [3016552] J Cell Biol. 1988 Nov;107(5):1707-15 [2846585] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1997 Sep;71(9):6582-92 [9261380] J Virol. 1998 Apr;72(4):2723-32 [9525590] Virology. 1997 Feb 17;228(2):294-306 [9123837] J Virol. 1997 May;71(5):3474-83 [9094619] EMBO J. 1997 Mar 17;16(6):1224-35 [9135139] J Virol. 1997 Jun;71(6):4409-18 [9151831] J Virol. 1997 Jul;71(7):5382-90 [9188609] J Virol. 1998 May;72(5):4116-26 [9557701] EMBO J. 1998 May 1;17(9):2699-708 [9564051] J Virol. 1998 Sep;72(9):7659-63 [9696871] J Virol. 1998 Dec;72(12):9621-7 [9811695] Virology. 1998 Nov 10;251(1):1-15 [9813197] J Virol. 1999 May;73(5):4136-44 [10196310] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4594-8 [8183954] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] J Virol. 1989 Nov;63(11):4670-5 [2677400] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):70-4 [1729720] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1992 Sep;66(9):5667-70 [1501299] J Virol. 1992 Nov;66(11):6489-95 [1357189] J Virol. 1993 Jan;67(1):407-14 [8380086] J Virol. 1993 Mar;67(3):1663-6 [8437236] J Virol. 1993 Jul;67(7):4386-90 [8510227] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Jan;68(1):441-7 [8254754] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Oct;68(10):6644-54 [7521919] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 May;69(5):2729-36 [7535863] J Virol. 1995 Nov;69(11):6810-8 [7474093] Cell. 1995 Nov 17;83(4):569-76 [7585960] J Virol. 1995 Dec;69(12):7630-8 [7494271] J Virol. 1996 Jan;70(1):341-51 [8523546] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] Virology. 1996 Apr 1;218(1):159-68 [8615019] J Virol. 1996 Aug;70(8):5297-305 [8764040] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12519-24 [8901614] J Virol. 1996 Dec;70(12):8645-52 [8970990] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolism of tricyclic antidepressants. AN - 69744555; 10319193 AB - 1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants (TCAs) remain an important option for the pharmacotherapy of depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic first-pass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TCAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications. JF - Cellular and molecular neurobiology AU - Rudorfer, M V AU - Potter, W Z AD - Division of Services and Intervention Research, National Institute of Mental Health, Bethesda, Maryland 20892-9635, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 373 EP - 409 VL - 19 IS - 3 SN - 0272-4340, 0272-4340 KW - Antidepressive Agents, Tricyclic KW - 0 KW - Index Medicus KW - Humans KW - Antidepressive Agents, Tricyclic -- pharmacokinetics KW - Antidepressive Agents, Tricyclic -- chemistry KW - Depression -- metabolism KW - Depression -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69744555?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+neurobiology&rft.atitle=Metabolism+of+tricyclic+antidepressants.&rft.au=Rudorfer%2C+M+V%3BPotter%2C+W+Z&rft.aulast=Rudorfer&rft.aufirst=M&rft.date=1999-06-01&rft.volume=19&rft.issue=3&rft.spage=373&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+neurobiology&rft.issn=02724340&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Species differences in cis-elements of the proalpha1(I) procollagen promoter and their binding proteins. AN - 69741870; 10321840 AB - Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the proalpha1(I) collagen promoter. One is the GC-rich A1 region (-194/168) that modulates transcriptional activity of the mouse promoter. The other contains a glucocorticoid response element (GRE) implicated in negative glucocorticoid regulation of the rat promoter. Unlike mouse A1 probes, probes representing the analogous human (-195/-168) and rat (-193/-179) regions failed to bind nuclear proteins in gel shift assays. Binding assays with mouse A1 probes containing base substitutions indicated that this behavior could be ascribed to five bases in the human, and two in the rat sequences. In addition, the pattern of expression of c-Krox, a protein that alters transcriptional activity via the mouse A1 element, differed in mouse and human tissues. Computer analysis revealed differences in the arrangement of GRE half-sites in human and rat proalpha1(I) collagen promoters. In a region of the human promoter (-700/673) analogous to the rat (-672/-633), there are three half-sites, each separated by two nucleotides, that cooperate in binding of glucocorticoid receptor. There also is a proximal half-site at position -335 of the human promoter that binds glucocorticoid receptor, but it is not present in the rat promoter. This study has defined several species-specific differences in the sequences and nuclear protein binding activity of regions involved in transcriptional activity of the proalpha1(I) collagen promoter. The results suggest that the A1 regions of the human and rat promoters examined here are unlikely to function as regulatory cis-elements, and they provide a framework for investigating the role of GREs in transcriptional regulation. They also suggest that species differences in cis-elements and transcription factors should be taken into consideration when using heterologous systems to study collagen gene regulation. JF - Journal of cellular biochemistry AU - Peterkofsky, B AU - Gosiewska, A AU - Singh, K AU - Pearlman, S AU - Mahmoodian, F AD - Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. peterkob@exchange.nih.gov Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 408 EP - 422 VL - 73 IS - 3 SN - 0730-2312, 0730-2312 KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Glucocorticoids KW - Procollagen KW - Transcription Factors KW - ZBTB7B protein, human KW - Zfp67 protein, mouse KW - Collagen KW - 9007-34-5 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Glucocorticoids -- metabolism KW - Blotting, Northern KW - Transcription Factors -- metabolism KW - Sequence Homology, Nucleic Acid KW - Collagen -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - HeLa Cells KW - Humans KW - Gene Expression KW - Mice KW - Mice, Inbred BALB C KW - Mutagenesis KW - Rats KW - Blotting, Western KW - Models, Genetic KW - Binding, Competitive KW - DNA-Binding Proteins -- metabolism KW - Promoter Regions, Genetic KW - Species Specificity KW - Procollagen -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69741870?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+biochemistry&rft.atitle=Species+differences+in+cis-elements+of+the+proalpha1%28I%29+procollagen+promoter+and+their+binding+proteins.&rft.au=Peterkofsky%2C+B%3BGosiewska%2C+A%3BSingh%2C+K%3BPearlman%2C+S%3BMahmoodian%2C+F&rft.aulast=Peterkofsky&rft.aufirst=B&rft.date=1999-06-01&rft.volume=73&rft.issue=3&rft.spage=408&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+biochemistry&rft.issn=07302312&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-02 N1 - Date created - 1999-08-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism. AN - 69737201; 10230772 AB - The tricyclic compound 2,5-bis(5-hydroxymethyl-2-thienyl)furan (NSC 652287) has shown a highly selective pattern of differential cytotoxic activity in the tumor cell lines comprising the National Cancer Institute (NCI) Anticancer Drug Screen. The mechanism underlying the selective cytotoxicity is unknown. We hypothesized that differential sensitivity to the compound observed in several renal tumor cell lines could be the result of selective accumulation or differential metabolism of this agent. We demonstrated here that the capacity of certain renal cell lines to accumulate and retain the compound, determined by accumulation of [14C]NSC 652287-derived radioactivity and by flow cytometric determination of unlabeled compound, paralleled the sensitivity of the renal cell lines to growth inhibition by NSC 652287: A-498 > TK-10 >> ACHN approximately/= to UO-31. The ability of the cell lines to metabolize [14C]NSC 652287 to a reactive species capable of binding covalently to cellular macromolecules also directly correlated with sensitivity to the compound. Different patterns of metabolites were generated by relatively more drug-sensitive cell lines in comparison with drug-resistant cell lines. The metabolizing capacity for NSC 652287 was localized primarily to the cytosolic (S100) fraction. The rate of metabolism in the cytosolic fraction from the most sensitive renal cell line, A-498, was faster than that observed in the cytosolic fractions from the other, less sensitive cell lines. The data support the hypothesis that both selective cellular accumulation and the capacity to metabolize NSC 652287 to a reactive species by certain renal carcinoma cell types are the basis for the differential cytotoxicity of this compound class. JF - Biochemical pharmacology AU - Rivera, M I AU - Stinson, S F AU - Vistica, D T AU - Jorden, J L AU - Kenney, S AU - Sausville, E A AD - Laboratory of Drug Discovery Research and Development, Division of Cancer Treatment and Diagnosis, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 1283 EP - 1295 VL - 57 IS - 11 SN - 0006-2952, 0006-2952 KW - Carbon Radioisotopes KW - 0 KW - Furans KW - NSC 652287 KW - Radiopharmaceuticals KW - Thiophenes KW - Index Medicus KW - Drug Screening Assays, Antitumor KW - Tumor Cells, Cultured KW - Humans KW - Flow Cytometry KW - Drug Resistance, Neoplasm KW - Carcinoma, Renal Cell -- pathology KW - Kidney Neoplasms -- pathology KW - Furans -- pharmacology KW - Furans -- metabolism KW - Thiophenes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69737201?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Selective+toxicity+of+the+tricyclic+thiophene+NSC+652287+in+renal+carcinoma+cell+lines%3A+differential+accumulation+and+metabolism.&rft.au=Rivera%2C+M+I%3BStinson%2C+S+F%3BVistica%2C+D+T%3BJorden%2C+J+L%3BKenney%2C+S%3BSausville%2C+E+A&rft.aulast=Rivera&rft.aufirst=M&rft.date=1999-06-01&rft.volume=57&rft.issue=11&rft.spage=1283&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adenosine-induced cell death: evidence for receptor-mediated signalling. AN - 69536286; 14634282 AB - Adenosine modulates the proliferation, survival and apoptosis of many different cell types, ranging from epithelial, endothelial and smooth muscle cells, to cells of the immune and neural lineages. In this review, we critically discuss the available in vitro and in vivo data which support a role for adenosine in both development-associated apoptosis, and in diseases characterized by either pathologically increased cell death (e.g., ischemia, trauma and aging-associated neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer). Particular emphasis is given to the possible role of extracellular adenosine receptors, since these may represent novel and attractive molecular targets for the pharmacological modulation of apoptosis. In some instances, adenosine-induced cell death has been demonstrated to require entry of the nucleoside inside cells; however, in many other cases, activation of specific adenosine extracellular receptors has been demonstrated. Of the four G protein-coupled adenosine receptors so far identified, the A2A and the A3 receptors have been specifically implicated in modulation of cell death. For the A3 receptor, results obtained by exposing both cardiomyocytes and brain astrocytes to graded concentrations of selective agonists suggest induction of both cell protection and cell death. Such opposite effects, which likely depend on the degree of receptor activation, may have important therapeutic implications in the pharmacological modulation of cardiac and brain ischemia. For the A2A receptor, recent intriguing data suggest a specific role in immune cell death and immunosuppression, which may be relevant to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized by accumulation of adenosine to toxic levels) and in tumors where induction of apoptosis via activation of specific extracellular receptors may be desirable. Finally, preliminary data suggest that, in a similar way to the adenosine-deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in degenerative muscular diseases may contribute to muscle cell death. Although the role of adenosine receptors in this effect still remains to be determined, these data suggest that adenosine-induced apoptosis may also represent a novel pathogenic pathway in muscular dystrophies. JF - Apoptosis : an international journal on programmed cell death AU - Jacobson, K A AU - Hoffmann, C AU - Cattabeni, F AU - Abbracchio, M P AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 197 EP - 211 VL - 4 IS - 3 SN - 1360-8185, 1360-8185 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69536286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Apoptosis+%3A+an+international+journal+on+programmed+cell+death&rft.atitle=Adenosine-induced+cell+death%3A+evidence+for+receptor-mediated+signalling.&rft.au=Jacobson%2C+K+A%3BHoffmann%2C+C%3BCattabeni%2C+F%3BAbbracchio%2C+M+P&rft.aulast=Jacobson&rft.aufirst=K&rft.date=1999-06-01&rft.volume=4&rft.issue=3&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Apoptosis+%3A+an+international+journal+on+programmed+cell+death&rft.issn=13608185&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2004-01-05 N1 - Date created - 2003-11-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oligonucleotides as transcription factor decoys. AN - 69509607; 11713803 AB - Cellular and molecular research has been focused to develop a means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiological conditions. A successful oligonucleotide-based approach has been the use of synthetic oligonucleotides containing an enhancer element that can penetrate cells, bind sequence-specific DNA-binding proteins and interfere with transcription in vivo. This review describes such decoy oligonucleotides that exhibit high affinity for a target transcription factor and successfully interfere with transcription in vivo. Evidence presented here shows that the decoy oligonucleotide technology offers great promise as a tool for defining cellular regulatory processes and for treating cancer, viral diseases and other pathological conditions. JF - Current opinion in molecular therapeutics AU - Cho-Chung, Y S AU - Park, Y G AU - Lee, Y N AD - National Cancer Institute, Bethesda, MD 20892-1750, USA. chochung@helix.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 386 EP - 392 VL - 1 IS - 3 SN - 1464-8431, 1464-8431 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - Gene Products, tat KW - NF-kappa B KW - Oligodeoxyribonucleotides KW - Reverse Transcriptase Inhibitors KW - Thionucleotides KW - Transcription Factors KW - DNA KW - 9007-49-2 KW - Cyclic AMP KW - E0399OZS9N KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Reverse Transcriptase Inhibitors -- chemistry KW - Drug Stability KW - Myocardial Infarction -- genetics KW - Cell Nucleus -- chemistry KW - Drug Design KW - Nucleic Acid Conformation KW - Angioplasty, Balloon, Coronary KW - HIV Reverse Transcriptase -- genetics KW - Second Messenger Systems -- physiology KW - Promoter Regions, Genetic -- drug effects KW - Tunica Intima -- metabolism KW - NF-kappa B -- antagonists & inhibitors KW - Reverse Transcriptase Inhibitors -- pharmacology KW - DNA -- metabolism KW - Tunica Intima -- drug effects KW - Glomerulonephritis -- genetics KW - Cyclic AMP -- physiology KW - NF-kappa B -- physiology KW - Recurrence KW - Coronary Stenosis -- prevention & control KW - Glomerulonephritis -- drug therapy KW - Structure-Activity Relationship KW - Regulatory Sequences, Nucleic Acid KW - Gene Products, tat -- antagonists & inhibitors KW - Protein Binding -- drug effects KW - Enhancer Elements, Genetic -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Genes, rev KW - Substrate Specificity KW - Cell Adhesion -- drug effects KW - Tunica Intima -- pathology KW - Gene Products, tat -- genetics KW - Genes, tat KW - Coronary Stenosis -- therapy KW - Myocardial Infarction -- drug therapy KW - Thionucleotides -- pharmacology KW - Transcription Factors -- antagonists & inhibitors KW - Oligodeoxyribonucleotides -- chemistry KW - Oligodeoxyribonucleotides -- pharmacology KW - Gene Expression Regulation -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69509607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+molecular+therapeutics&rft.atitle=Oligonucleotides+as+transcription+factor+decoys.&rft.au=Cho-Chung%2C+Y+S%3BPark%2C+Y+G%3BLee%2C+Y+N&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=1999-06-01&rft.volume=1&rft.issue=3&rft.spage=386&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+molecular+therapeutics&rft.issn=14648431&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-12-31 N1 - Date created - 2001-11-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Summarizing the motion of self-propelled cells: applications to sperm motility. AN - 69508340; 11318211 AB - Proper characterization of the motion of spermatozoa is an important prerequisite for interpreting differences in sperm motility that might arise from exposure to toxicants. Patterns of sperm movement can be extremely complex. On the basis of an exponential model that relates the discretely approximated curvilinear velocity to the tracking rate, we develop a statistic that indexes the predictability of the path for individual sperm. We summarize the path of each sperm using this and two other statistics: (1) the path displacement velocity and (2) linearity of movement. We apply the method to a set of rat sperm tracks representative of both normal and abnormal motion characteristics. JF - Biometrics AU - Dunson, D B AU - Weinberg, C R AU - Perreault, S D AU - Chapin, R E AD - Biostatistics Branch, NIEHS, Research Triangle Park, North Carolina 27709, USA. dunson1@niehs.nih.gov Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 537 EP - 543 VL - 55 IS - 2 SN - 0006-341X, 0006-341X KW - Index Medicus KW - Rats KW - Cell Movement KW - Fractals KW - Animals KW - Computers KW - In Vitro Techniques KW - Models, Biological KW - Spermatozoa -- abnormalities KW - Male KW - Biometry KW - Sperm Motility UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69508340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Summarizing+the+motion+of+self-propelled+cells%3A+applications+to+sperm+motility.&rft.au=Dunson%2C+D+B%3BWeinberg%2C+C+R%3BPerreault%2C+S+D%3BChapin%2C+R+E&rft.aulast=Dunson&rft.aufirst=D&rft.date=1999-06-01&rft.volume=55&rft.issue=2&rft.spage=537&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-24 N1 - Date created - 2001-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The use of transgenic animals in cancer testing. AN - 69501296; 11202994 JF - Inhalation toxicology AU - French, J E AU - Spalding, J W AU - Dunnick, J K AU - Tice, R R AU - Furedi-Machacek, M AU - Tennant, R W AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1999 SP - 541 EP - 544 VL - 11 IS - 6-7 SN - 0895-8378, 0895-8378 KW - Index Medicus KW - Animals KW - Genes, ras -- genetics KW - Mice KW - Mice, Transgenic KW - Carcinogenicity Tests KW - Animals, Genetically Modified -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69501296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Inhalation+toxicology&rft.atitle=The+use+of+transgenic+animals+in+cancer+testing.&rft.au=French%2C+J+E%3BSpalding%2C+J+W%3BDunnick%2C+J+K%3BTice%2C+R+R%3BFuredi-Machacek%2C+M%3BTennant%2C+R+W&rft.aulast=French&rft.aufirst=J&rft.date=1999-06-01&rft.volume=11&rft.issue=6-7&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=Inhalation+toxicology&rft.issn=08958378&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-10-30 N1 - Date created - 2000-10-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorylation of Drosophila heat shock transcription factor. AN - 69225758; 10547060 AB - The role that phosphorylation plays in regulating heat shock factor (HSF) function and activity has been the subject of several studies. Here, we demonstrate that Drosophila melanogaster HSF (DmHSF) is a phosphoprotein that is multiply phosphorylated at some sites and is dephosphorylated at others upon heat shock. However, the steady-state level of phosphorylation of Drosophila HSF remains unchanged after heat shock. Phosphoamino-acid analysis reveals that predominantly serine residues are phosphorylated for both the non-shocked and heat shocked molecules. Gel mobility shift assays using extracts from SL2 cells treated with a variety of phosphatase and kinase inhibitors show little or no effect on the heat shock induced DNA binding activity of HSF or on its recovery. We conclude that phosphorylation plays no significant role in regulating the heat induced DNA binding activity of Drosophila HSF. JF - Cell stress & chaperones AU - Fritsch, M AU - Wu, C AD - Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 102 EP - 117 VL - 4 IS - 2 SN - 1355-8145, 1355-8145 KW - DNA-Binding Proteins KW - 0 KW - Enzyme Inhibitors KW - Heat-Shock Proteins KW - Transcription Factors KW - heat shock transcription factor KW - Okadaic Acid KW - 1W21G5Q4N2 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Hot Temperature KW - Animals KW - Phosphorylation KW - DNA -- metabolism KW - Electrophoresis, Gel, Two-Dimensional KW - Okadaic Acid -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Drosophila KW - Cell Line KW - Heat-Shock Proteins -- metabolism KW - Transcription Factors -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69225758?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+stress+%26+chaperones&rft.atitle=Phosphorylation+of+Drosophila+heat+shock+transcription+factor.&rft.au=Fritsch%2C+M%3BWu%2C+C&rft.aulast=Fritsch&rft.aufirst=M&rft.date=1999-06-01&rft.volume=4&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Cell+stress+%26+chaperones&rft.issn=13558145&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-19 N1 - Date created - 1999-11-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enhanced free radical generation of FALS-associated Cu,Zn-SOD mutants AN - 20140128; 10262811 AB - Familial amyotrophic lateral sclerosis (FALS) is an inherited disorder of motor neurons, which is associated with missense mutations in the Cu,Zn-super-oxide dismutase (Cu,Zn-SOD) gene. Mice from the G93A transgenic line was reported to develop a syndrome of FALS. The fact that the symptoms occurred against a background of normal mouse Cu,Zn-SOD activity suggests that dominant, gain-of-function mutations in SOD play a role in the pathogenesis of FALS. We investigated the nature of this gain-of-function of FALS mutants. We have previously reported that Cu,Zn-SOD has the free radical-generating function in addition to normal dismutation activity. These two enzymic activities were compared by using mutants (G93A and A4V) and the wild-type Cu,Zn-SOD prepared by recombinant method. Our results showed that the wild-type, G93A, and A4V enzymes have identical dismutation activity. However, the free radical-generating function of the G93A and A4V mutants, as measured by the spin trapping and EPR method, is enhanced relative to that of the wild-type enzyme (wild-type G93A > A4V. The catalytic activity to generate free radicals is correlated to the clinical severity of the disorder induced by these mutant enzymes. Furthermore, we found that intact FALS mutants failed to enhance tyrosine nitration. Together, our results indicate that the amyotrophic lateral sclerosis symptoms are not caused by the reduction of Cu,Zn-SOD dismutation activity with the mutant enzymes; rather, it is induced in part by enhancement of the free radical-generating function. JF - Neurotoxicity Research AU - Yim, Moon B AU - Yim, Hyung-Soon AU - Chock, P Boon AU - Stadtman, Earl R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 3, Room 202, MSC-0342, 20892 Bethesda, MD, USA, yimm@gwgate.nhlbi.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 91 EP - 97 PB - Taylor & Francis Group Ltd., 2 Park Square Milton Park, Abingdon Oxford OX14 4RN UK, [URL:http://www.taylorandfrancis.co.uk/] VL - 1 IS - 2 SN - 1029-8428, 1029-8428 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - E.S.R. KW - Missense mutation KW - Hereditary diseases KW - Free radicals KW - Tyrosine KW - Enzymes KW - Trapping KW - Motor neurons KW - Amyotrophic lateral sclerosis KW - Superoxide dismutase KW - Hydrogen peroxide KW - Neurotoxicity KW - Nitration KW - N3 11027:Neurology & neuropathology KW - X 24300:Methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20140128?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicity+Research&rft.atitle=Enhanced+free+radical+generation+of+FALS-associated+Cu%2CZn-SOD+mutants&rft.au=Yim%2C+Moon+B%3BYim%2C+Hyung-Soon%3BChock%2C+P+Boon%3BStadtman%2C+Earl+R&rft.aulast=Yim&rft.aufirst=Moon&rft.date=1999-06-01&rft.volume=1&rft.issue=2&rft.spage=91&rft.isbn=&rft.btitle=&rft.title=Neurotoxicity+Research&rft.issn=10298428&rft_id=info:doi/10.1007%2FBF03033273 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2009-08-01 N1 - Last updated - 2015-03-30 N1 - SubjectsTermNotLitGenreText - E.S.R.; Missense mutation; Hereditary diseases; Free radicals; Enzymes; Tyrosine; Trapping; Motor neurons; Amyotrophic lateral sclerosis; Hydrogen peroxide; Superoxide dismutase; Neurotoxicity; Nitration DO - http://dx.doi.org/10.1007/BF03033273 ER - TY - JOUR T1 - Re-engineering the Functions of a Terminally Differentiated Epithelial Cell in Vivo AN - 1846400600; PQ0003825809 AB - ABSTRACT: Because of their easy access, and important role in oral homeostasis, mammalian salivary glands provide a unique site for addressing key issues and problems in tissue engineering. This manuscript reviews studies by us in three major directions involving re-engineering functions of salivary epithelial cells. Using adenoviral-mediated gene transfer in vivo, we show approaches to i) repair damaged, hypofunctional glands and ii) redesign secretory functions to include endocrine as well as exocrine pathways. The third series of studies show our general approach to develop an artificial salivary gland for clinical situations in which all glandular tissue has been lost. JF - Annals of the New York Academy of Sciences AU - Baum, Bruce J AU - Wang, Songlin AU - Cukierman, Edna AU - Delporte, Christine AU - Kagami, Hideaki AU - Marmary, Yitzhak AU - Fox, Philip C AU - Mooney, David J AU - Yamada, Kenneth M AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/06// PY - 1999 DA - June 1999 SP - 294 EP - 300 PB - Wiley-Blackwell, 111 River Street Hoboken NJ 07030-5774 United States VL - 875 IS - 1 SN - 0077-8923, 0077-8923 KW - Immunology Abstracts; Environment Abstracts KW - Tissues KW - Digestive glands KW - ENA 21:Wildlife UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1846400600?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=Re-engineering+the+Functions+of+a+Terminally+Differentiated+Epithelial+Cell+in+Vivo&rft.au=Baum%2C+Bruce+J%3BWang%2C+Songlin%3BCukierman%2C+Edna%3BDelporte%2C+Christine%3BKagami%2C+Hideaki%3BMarmary%2C+Yitzhak%3BFox%2C+Philip+C%3BMooney%2C+David+J%3BYamada%2C+Kenneth+M&rft.aulast=Baum&rft.aufirst=Bruce&rft.date=1999-06-01&rft.volume=875&rft.issue=1&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/10.1111%2Fj.1749-6632.1999.tb08512.x LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2016-12-01 N1 - Last updated - 2016-12-22 N1 - SubjectsTermNotLitGenreText - Tissues; Digestive glands DO - http://dx.doi.org/10.1111/j.1749-6632.1999.tb08512.x ER - TY - JOUR T1 - Identification of surface molecules on salivary glands of the mosquito, Aedes aegypti, by a panel of monoclonal antibodies AN - 17600345; 4726883 AB - Malaria transmission by the mosquito vector requires sporozoite invasion into mosquito salivary glands. Parasites probably enter the glands by specific receptor--ligand interactions with molecules on the surface of the glands. We have undertaken the characterization of salivary gland surface molecules of Aedes aegypti to identify candidate receptors for Plasmodium gallinaceum sporozoite invasion. Monoclonal antibodies (mAbs) were generated against antigen enriched for salivary gland membranes and basal lamina. A panel of 44 mAbs were generated that bound to surface molecules of mosquito tissues. Twenty-four mAbs bound exclusively to salivary glands, six bound to salivary glands and ovaries, one bound to salivary gland and midgut, and 13 bound to all tissues tested. We present data on the immunolocalization and biochemical characteristics of the antigens. Many of the salivary gland-specific mAbs bound preferentially to the median and distal lateral lobes of the salivary glands, indicating that there arc anatomical region-specific biochemical differences on the gland surface. These lobes of the salivary glands are the preferential sites of malaria sporozoite invasion. Therefore, antigens specific for these regions are promising candidate receptors for sporozoite invasion. The present identification of surface molecules of mosquito salivary glands by means of monoclonal antibodies represents the first description of individual molecules on the mosquito salivary gland surface. This work lays the basis for further studies on the molecular mechanisms involved in malaria sporozoite invasion of mosquito salivary glands. JF - Insect Biochemistry and Molecular Biology AU - Barreau, C AU - Conrad, J AU - Fischer, E AU - Lujan, H D AU - Vernick, K D AD - Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health,, Bethesda, MD 20892 USA Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 515 EP - 526 VL - 29 IS - 6 SN - 0965-1748, 0965-1748 KW - Diptera KW - Mosquitoes KW - Yellow fever mosquito KW - salivary glands KW - sporozoite invasion KW - ASFA 1: Biological Sciences & Living Resources; ASFA 3: Aquatic Pollution & Environmental Quality; Entomology Abstracts KW - Biological vectors KW - Parasites KW - Aedes aegypti KW - Human diseases KW - Protozoan diseases KW - Monoclonal antibodies KW - Brackish KW - Culicidae KW - Malaria KW - Freshwater KW - Salivary gland KW - Disease transmission KW - Public health KW - Antibodies KW - Antigens KW - Glands KW - Plasmodium gallinaceum KW - Ligands KW - Q1 08484:Species interactions: parasites and diseases KW - Q5 08524:Public health, medicines, dangerous organisms KW - Z 05179:Glands & secretions UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17600345?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aasfaaquaticpollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Insect+Biochemistry+and+Molecular+Biology&rft.atitle=Identification+of+surface+molecules+on+salivary+glands+of+the+mosquito%2C+Aedes+aegypti%2C+by+a+panel+of+monoclonal+antibodies&rft.au=Barreau%2C+C%3BConrad%2C+J%3BFischer%2C+E%3BLujan%2C+H+D%3BVernick%2C+K+D&rft.aulast=Barreau&rft.aufirst=C&rft.date=1999-06-01&rft.volume=29&rft.issue=6&rft.spage=515&rft.isbn=&rft.btitle=&rft.title=Insect+Biochemistry+and+Molecular+Biology&rft.issn=09651748&rft_id=info:doi/10.1016%2FS0965-1748%2899%2900025-9 LA - English DB - ProQuest Environmental Science Collection N1 - Last updated - 2014-05-06 N1 - SubjectsTermNotLitGenreText - Biological vectors; Parasites; Human diseases; Antibodies; Antigens; Protozoan diseases; Glands; Malaria; Ligands; Public health; Disease transmission; Monoclonal antibodies; Salivary gland; Aedes aegypti; Plasmodium gallinaceum; Culicidae; Freshwater; Brackish DO - http://dx.doi.org/10.1016/S0965-1748(99)00025-9 ER - TY - JOUR T1 - Organochlorines in breast milk from two cities in Ukraine AN - 17383752; 4604609 AB - Reports of environmental problems in the former Soviet Union, including excess use of pesticides, have led to concerns about high levels of contamination in humans, but little information is available to assess whether these concerns are warranted. Samples of breast milk from 197 women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, beta -hexachlorocyclohexane (HCH), and 18 polychlorinated biphenyl congeners, and results were compared to previous reports from Europe. The median beta -HCH concentration was 731 ng/g milk fat, which is higher than other reports from Europe but lower than reports from other parts of the world. The median DDE concentration was 2,457 ng/g milk fat, which is higher than most but not all other reports from Europe. Concentrations of other chemicals were comparable to or lower than other reports from Europe. Concentrations from the city of Kyiv were generally lower than those from Dniprodzerzhinsk, but the magnitudes of these differences were modest. JF - Environmental Health Perspectives AU - Gladen, B C AU - Monaghan, S C AU - Lukyanova, E M AU - Hulchiy, O P AU - Shkyryak-Nyzhnyk, Z A AU - Sericano, J L AU - Little, R E AD - Biostatistics Branch, Mail Drop A3-03, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709 USA, gladen@niehs.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 459 EP - 462 VL - 107 IS - 6 SN - 0091-6765, 0091-6765 KW - man KW - Ukraine KW - hexachlorobenzene KW - oxychlordane KW - Pollution Abstracts; Toxicology Abstracts; Health & Safety Science Abstracts KW - Organochlorine compounds KW - Dieldrin KW - Breast milk KW - Pesticides (organochlorine) KW - Pesticides KW - Hexachlorobenzene KW - X 24120:Food, additives & contaminants KW - X 24153:Metabolism KW - H 4000:Food and Drugs KW - P 6000:TOXICOLOGY AND HEALTH UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17383752?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Organochlorines+in+breast+milk+from+two+cities+in+Ukraine&rft.au=Gladen%2C+B+C%3BMonaghan%2C+S+C%3BLukyanova%2C+E+M%3BHulchiy%2C+O+P%3BShkyryak-Nyzhnyk%2C+Z+A%3BSericano%2C+J+L%3BLittle%2C+R+E&rft.aulast=Gladen&rft.aufirst=B&rft.date=1999-06-01&rft.volume=107&rft.issue=6&rft.spage=459&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dieldrin; Pesticides; Organochlorine compounds; Breast milk; Hexachlorobenzene; Pesticides (organochlorine) ER - TY - CONF T1 - Evolutionary game theory and multiple chemical sensitivity AN - 17381066; 4609229 AB - Newlin's [Newlin D.B. Evolutionary game theory of tolerance and sensitization in substance abuse. Paper presented to the Research Society on Alcoholism, Hilton Head, SC, 1998] evolutionary game theory of addictive behavior specifies how evolutionarily stable strategies for survival and reproduction may lead to addiction. The game theory of multiple chemical sensitivity (MCS) assumes that: (1) the MCS patient responds to low-level toxicants as stressors or as direct threats to their survival and reproductive fitness, (2) this activates the cortico-mesolimbic dopamine system, (3) this system is a survival motivation center--not a `reward center', (4) the subject emits a counter-response that is in the same direction as the naive response to the chemicals, (5) previously neutral stimuli associated with chemicals also trigger conditioned responses that mimic those to the chemicals, (6) these counter-responses further activate the dopaminergic survival motivation system, and (7) this produces a positive feedback loop that leads to strong neural sensitization in these structures and in behavior controlled by this system, despite a small initial response. Psychologically, the MCS patient with a sensitized cortico-mesolimbic dopamine system is behaving as though his/her survival is directly threatened by these chemicals. Non-MCS subjects have counter-responses opposite in direction to those of the chemicals and show tolerance. An autoshaping/sign-tracking model of this game is discussed. This evolutionary game makes several specific, testable predictions about differences between MCS subjects, non-MCS controls, and substance abusers in laboratory experiments, and between sensitized and nonsensitized animals. JF - Toxicology and Industrial Health AU - Newlin, D B Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 313 EP - 322 PB - Princeton Scientific Publishing Co. Inc., Box 2155 Princeton NJ 08543 USA VL - 15 IS - 3-4 KW - Toxicology Abstracts KW - multiple chemical sensitivity KW - Addiction KW - Evolution KW - X 24240:Miscellaneous UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17381066?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Industrial+Health&rft.atitle=Evolutionary+game+theory+and+multiple+chemical+sensitivity&rft.au=Newlin%2C+D+B&rft.aulast=Newlin&rft.aufirst=D&rft.date=1999-06-01&rft.volume=15&rft.issue=3-4&rft.spage=313&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Industrial+Health&rft.issn=07482337&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Effects of Fixation on RNA Extraction and Amplification from Laser Capture Microdissected Tissue AN - 17374785; 4562229 AB - One of the key end points for understanding the molecular basis of carcinogenesis is the quantitation of gene expression in specific cell populations. Microdissection techniques allow extraction of morphologically distinct cells for molecular analysis. A recent advance in microdissection uses the PixCell laser capture microdissection (LCM) system, which allows for precise removal of pure cell populations from morphologically preserved tissue sections. The objective of this study was to determine the optimal fixation protocol for analyzing RNA from tissue samples using LCM. Optimal fixation must provide acceptable morphology, allow proper laser capture of selected cells, and preserve the integrity of mRNA. We evaluated the effects of both cross-linking and precipitive-type fixatives on frozen and paraffin-embedded mouse liver tissue. For assessment of the quality of the mRNA in LCM samples generated from various fixed tissues, reverse transcription-polymerase chain reaction (RT-PCR)-amplified mouse liver beta sub(2)-microglobulin mRNA was detected with ethidium bromide. We also examined mouse glyceraldehyde-3-phosphate-dehydrogenase by using the fluorogenic TaqMan system for real-time quantitative detection of RT-PCR products. Frozen tissues yielded more RT-PCR product than did paraffin-embedded tissues. In both frozen and paraffin-embedded tissues, differences were observed between the fixatives. Precipitive fixatives, such as ethanol and acetone, consistently produced more RT-PCR amplification product than did cross-linking fixatives such as formalin. Optimal fixation protocols for LCM analysis will facilitate the examination of gene expression in specific cell populations, accelerating investigations of the molecular differences responsible for the phenotypic changes observed during carcinogenesis. JF - Molecular Carcinogenesis AU - Goldsworthy, S M AU - Stockton, P S AU - Trempus, C S AU - Foley, J F AU - Maronpot, R R AD - Laboratory of Experimental Pathology, Building 101, MD C2-01, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 86 EP - 91 VL - 25 IS - 2 SN - 0899-1987, 0899-1987 KW - RNA extraction KW - laser capture microdissection KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene amplification KW - Polymerase chain reaction KW - Lasers KW - Dissection KW - W3 33243:Molecular methods KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17374785?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Effects+of+Fixation+on+RNA+Extraction+and+Amplification+from+Laser+Capture+Microdissected+Tissue&rft.au=Goldsworthy%2C+S+M%3BStockton%2C+P+S%3BTrempus%2C+C+S%3BFoley%2C+J+F%3BMaronpot%2C+R+R&rft.aulast=Goldsworthy&rft.aufirst=S&rft.date=1999-06-01&rft.volume=25&rft.issue=2&rft.spage=86&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/10.1002%2F%28SICI%291098-2744%28199906%2925%3A23.3.CO%3B2-W LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lasers; Dissection; Gene amplification; Polymerase chain reaction DO - http://dx.doi.org/10.1002/(SICI)1098-2744(199906)25:2<86::AID-MC2>3.3.CO;2-W ER - TY - JOUR T1 - Association between alcohol and lung cancer in the alpha-tocopherol, beta-carotene cancer prevention study in Finland AN - 17361764; 4581302 AB - Objectives: We evaluated the association between alcohol intake and lung cancer in a trial-based cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). Methods: During an average of 7.7 years of follow-up, 1059 lung cancer cases were diagnosed among the 27,111 male smokers with complete alcohol and dietary information. The relationship between alcohol and lung cancer was assessed in multivariate Cox regression models that adjusted for age, smoking, body mass index and intervention group. Results: Nondrinkers, 11% of the study population, were at increased lung cancer risk compared to drinkers (RR = 1.2, 95% CI: 1.0-1.4), possibly due to the inclusion of ex-drinkers who had stopped drinking for health reasons. Among drinkers only, we observed no association between lung cancer and total ethanol or specific beverage (beer, wine, spirits) intake. We found no significant effect modification by level of smoking, dietary micronutrients or trial intervention group; however, for men in the highest quartile of alcohol intake, we observed a slight increase in risk for lighter smokers (30 cigarettes/day). Conclusions: We concluded that alcohol consumption was not a risk factor for lung cancer among male cigarette smokers, and its effect was not significantly modified by other factors, notably smoking history. JF - Cancer Causes & Control AU - Woodson, K AU - Albanes, D AU - Tangrea, JA AU - Rautalahti, M AU - Virtamo, J AU - Taylor, PR AD - Cancer Prevention Studies Branch, 6006 Executive Boulevard - Suite 321, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892-7058, USA Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 219 EP - 226 VL - 10 IS - 3 SN - 0957-5243, 0957-5243 KW - man KW - Finland KW - beta -Carotene KW - beta carotene KW - Health & Safety Science Abstracts; Toxicology Abstracts KW - ^b-Carotene KW - Diets KW - Vitamin E KW - Lung KW - Carcinogenesis KW - Cigarette smoking KW - Ethanol KW - Lung cancer KW - H 11000:Diseases/Injuries/Trauma KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17361764?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Association+between+alcohol+and+lung+cancer+in+the+alpha-tocopherol%2C+beta-carotene+cancer+prevention+study+in+Finland&rft.au=Woodson%2C+K%3BAlbanes%2C+D%3BTangrea%2C+JA%3BRautalahti%2C+M%3BVirtamo%2C+J%3BTaylor%2C+PR&rft.aulast=Woodson&rft.aufirst=K&rft.date=1999-06-01&rft.volume=10&rft.issue=3&rft.spage=219&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/10.1023%2FA%3A1008911624785 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cigarette smoking; Lung cancer; Diets; Ethanol; Lung; Carcinogenesis; Vitamin E DO - http://dx.doi.org/10.1023/A:1008911624785 ER - TY - JOUR T1 - Risk of premenopausal breast cancer in association with occupational exposure to polycyclic aromatic hydrocarbons and benzene AN - 17315408; 4586375 AB - This study examined the relationship between risk of premenopausal breast cancer and occupational exposure to benzene and polycyclic aromatic hydrocarbons (PAH) and whether the proposed relationship between PAH and breast cancer differed by tumor estrogen receptor (ER) status. In a case-referent study of premenopausal breast cancer, occupational histories and other information were obtained through interviews, and job-exposure matrices were used to assess exposure to PAH and benzene. A dose-response relationship for the probability of exposure to benzene [low: odds ratio (OR) 1.64, 95% confidence interval (95% CI) 0.64--4.21; high: OR 1.95, 95% CI 1.14--3.33) and to PAH (low: OR 1.56, 95% CI 0.78--3.12; high: OR 2.40, 95% CI 0.96--6.01). Risk increased with duration of exposure to benzene, but not to PAH. A dose-response relationship was not evident for the intensity of exposure to benzene or to PAH. When analyses were stratified by tumor ER status, PAH exposure was related to a greater increase in the risk of ER-positive (OR 2.27, 95% CI 1.14--4.54) than ER-negative (OR 1.12, 95% CI 0.47--2.64) breast cancer. Risk of ER-positive, but not ER-negative, tumors increased with the probability of exposure to PAH. The findings suggest an association between risk and occupational exposure to benzene. Although it was difficult to study PAH independently of benzene, there was some suggestion of an association between PAH exposure and ER-positive tumors. These data should be interpreted with caution because of the limitations of this study, including low-response rates and small numbers of exposed persons. JF - Scandinavian Journal of Work, Environment & Health AU - Petralia, SA AU - Vena, JE AU - Freudenheim, J L AU - Dosemeci, M AU - Michalek, A AU - Goldberg AU - Brasure, J AU - Graham, S AD - Occupational Epidemiology Branch, National Cancer Institute, Executive Plaza South Rm 8110, 6120 Executive Blvd, Bethesda, MD 20892, USA, sp126i@nih.com Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 215 EP - 221 VL - 25 IS - 3 SN - 0355-3140, 0355-3140 KW - benzene KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Polycyclic aromatic hydrocarbons KW - Breast cancer KW - Occupational exposure KW - R2 23080:Industrial and labor KW - H 1000:Occupational Safety and Health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17315408?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.atitle=Risk+of+premenopausal+breast+cancer+in+association+with+occupational+exposure+to+polycyclic+aromatic+hydrocarbons+and+benzene&rft.au=Petralia%2C+SA%3BVena%2C+JE%3BFreudenheim%2C+J+L%3BDosemeci%2C+M%3BMichalek%2C+A%3BGoldberg%3BBrasure%2C+J%3BGraham%2C+S&rft.aulast=Petralia&rft.aufirst=SA&rft.date=1999-06-01&rft.volume=25&rft.issue=3&rft.spage=215&rft.isbn=&rft.btitle=&rft.title=Scandinavian+Journal+of+Work%2C+Environment+%26+Health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast cancer; Occupational exposure; Risk assessment; Polycyclic aromatic hydrocarbons ER - TY - CONF T1 - Implications for atypical antioxidative properties of manganese in iron-induced brain lipid peroxidation and copper-dependent low density lipoprotein conjugation AN - 17306799; 4584224 AB - Our group recently observed that manganese prevents oxidative brain injury in the iron-induced parkinsonian animal model. It has also been suggested that manganese retards while copper promotes the development of atherosclerosis. In this report, we provide further evidence to support a controversial notion that manganese is an atypical antioxidant. Among transition metals, Cu super(2+) and Fe super(2+) (0.1 to 125 mu M), but not Mn super(2+), converted hydrogen peroxide to reactive hydroxyl radicals via the Fenton reaction at pH 7.4. Iron's pro-oxidative rate is relatively slow, but it is accelerated further by ascorbate (50 mu M) in 37 degree C Dulbecco's phosphate buffered saline. Moreover, Mn super(2+) (0-80 mu M) concentration dependently retarded diene conjugation of human low density lipoproteins stimulated by 5 mu M Cu super(2+). This new result is consistent with our recent finding that Mn super(2+) (0 to 20 mu M) does not initiate brain lipid peroxidation while it inhibits iron-induced peroxidation of polyunsaturated fatty acids. These unexpected manganese results are somewhat at odds with a prominent theory that manganese is a pro-oxidative transition metal. Furthermore, iron and copper induced free radical generation and lipid peroxidation are suppressed by lowering the incubation temperature; this suggests that hypothermia may decrease the oxidative stress and damage in vivo. In conclusion, normal dietary intake of manganese may protect cells and neurons from oxidant stress through the inhibition of propagation of lipid peroxidation caused by hydroxyl radicals generated by pro-oxidative transition metals such as iron and copper. Potential therapeutical uses of manganese, manganese SOD mimetics and hypothermia for protecting brain neurons and vascular endothelial cells against oxidative stress and damage have been successfully demonstrated in both animal models and clinical trials. JF - Neurotoxicology AU - Sziraki, I AU - Rauhala, P AU - Koh, Kwang Kon AU - Van Bergen, P AU - Chiueh, C C Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 455 EP - 466 PB - Intox Press VL - 20 IS - 2-3 KW - CSA Neurosciences Abstracts; Toxicology Abstracts KW - Neuroprotection KW - Copper KW - Lipid peroxidation KW - Lipoproteins (low density) KW - Oxidative stress KW - Neurotoxicity KW - Manganese KW - Iron KW - N3 11095:Neuroprotective agents KW - X 24165:Biochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17306799?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neurotoxicology&rft.atitle=Implications+for+atypical+antioxidative+properties+of+manganese+in+iron-induced+brain+lipid+peroxidation+and+copper-dependent+low+density+lipoprotein+conjugation&rft.au=Sziraki%2C+I%3BRauhala%2C+P%3BKoh%2C+Kwang+Kon%3BVan+Bergen%2C+P%3BChiueh%2C+C+C&rft.aulast=Sziraki&rft.aufirst=I&rft.date=1999-06-01&rft.volume=20&rft.issue=2-3&rft.spage=455&rft.isbn=&rft.btitle=&rft.title=Neurotoxicology&rft.issn=0161813X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 ER - TY - JOUR T1 - Recombinant Virus Vaccination against "Self" Antigens Using Anchor-fixed Immunogens AN - 17302249; 4575636 AB - To study the induction of anti-"self" CD8 super(+) T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 K super(b) molecule (A2/K super(b)). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8 super(+) T cells specific for the wild-type gp100 sub(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/K super(b)-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens. JF - Cancer Research AU - Irvine, K R AU - Parkhurst, M R AU - Shulman, E P AU - Tupesis, J P AU - Custer, M AU - Touloukian, CE AU - Robbins, P F AU - Yafal, A G AU - Greenhalgh, P AU - Sutmuller, RPM AU - Offringa, R AU - Rosenberg, SA AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, NIH, Building 10, Room 2B42 Bethesda, MD 20892, USA, restifo@nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 2536 EP - 2540 VL - 59 IS - 11 SN - 0008-5472, 0008-5472 KW - B16 cells KW - CD8 antigen KW - histocompatibility antigen H-2 KW - histocompatibility antigen HLA KW - mice KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Lymphocytes T KW - Vaccines KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17302249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Recombinant+Virus+Vaccination+against+%22Self%22+Antigens+Using+Anchor-fixed+Immunogens&rft.au=Irvine%2C+K+R%3BParkhurst%2C+M+R%3BShulman%2C+E+P%3BTupesis%2C+J+P%3BCuster%2C+M%3BTouloukian%2C+CE%3BRobbins%2C+P+F%3BYafal%2C+A+G%3BGreenhalgh%2C+P%3BSutmuller%2C+RPM%3BOffringa%2C+R%3BRosenberg%2C+SA%3BRestifo%2C+N+P&rft.aulast=Irvine&rft.aufirst=K&rft.date=1999-06-01&rft.volume=59&rft.issue=11&rft.spage=2536&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccines; Lymphocytes T ER - TY - JOUR T1 - Retrovirus-mediated WASP gene transfer corrects defective actin polymerization in B cell lines from Wiskott-Aldrich syndrome patients carrying `null' mutations AN - 17301938; 4559391 AB - Boys affected with Wiskott-Aldrich syndrome (WAS) present with variable association of thrombocytopenia, eczema and immune deficiency. If untreated, WAS patients may succumb to intracerebral hemorrhages, severe infections or malignancies. Allogeneic bone marrow transplantation (BMT) can cure all aspects of the disease, but HLA-identical donors are not available to all patients and mismatched BMTs are unfortunately associated with high mortality and morbidity. The good success of HLA-matched BMT, however, makes WAS a potential candidate for hematopoietic stem cell gene therapy. WAS patients carry mutations of the Wiskott-Aldrich syndrome protein gene encoding WASP, a 502-amino acid proline-rich protein with demonstrated involvement in the organization of the actin cytoskeleton. To verify the feasibility of genetic correction for this disease, the WASP cDNA was expressed in EBV-immortalized B cell lines obtained from WAS patients using a retroviral vector. Transduced WAS cells showed levels of WASP expression similar to those found in cells from normal donors, without detectable effects on viability or growth characteristics. In addition, retrovirus-mediated expression of WASP led to improvement of cytoplasmic F-actin expression and formation of F-actin-positive microvilli, a process shown to be defective in untransduced WAS cell lines. These preliminary results indicate a potential use for retrovirus-mediated gene transfer as therapy for WAS. JF - Gene Therapy AU - Candotti, F AU - Facchetti, F AU - Blanzuoli, L AU - Stewart, D M AU - Nelson, D L AU - Blaese, R M AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10C103, Bethesda, MD 20892-1851, USA Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 1170 EP - 1174 VL - 6 IS - 6 SN - 0969-7128, 0969-7128 KW - WASP protein KW - retrovirus KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Wiskott-Aldrich syndrome KW - Retrovirus KW - Actin KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17301938?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Retrovirus-mediated+WASP+gene+transfer+corrects+defective+actin+polymerization+in+B+cell+lines+from+Wiskott-Aldrich+syndrome+patients+carrying+%60null%27+mutations&rft.au=Candotti%2C+F%3BFacchetti%2C+F%3BBlanzuoli%2C+L%3BStewart%2C+D+M%3BNelson%2C+D+L%3BBlaese%2C+R+M&rft.aulast=Candotti&rft.aufirst=F&rft.date=1999-06-01&rft.volume=6&rft.issue=6&rft.spage=1170&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Retrovirus; Wiskott-Aldrich syndrome; Gene therapy; Actin ER - TY - JOUR T1 - In vitro anti-human immunodeficiency virus activities of Z- and E-methylenecyclopropane nucleoside analogues and their phosphoro-L-alaninate diesters AN - 17291584; 4559036 AB - Nucleoside analogues with a Z- or an E-methylenecyclopropane moiety were synthesized and examined for activity against human immunodeficiency virus type 1 (HIV-1) in vitro. The addition of a methyl phenyl phosphoro-L-alaninate moiety to modestly active analogues resulted in potentiation of their anti-HIV-1 activity. Two such compounds, designated QYL-685 (with 2,6-diaminopurine) and QYL-609 (with adenine), were most potent against HIV-1 in vitro, with 50% inhibitory concentrations of 0.034 and 0.0026 mu M, respectively, in MT-2 cell-based assays. Both compounds were active against zidovudine-resistant, didanosine-resistant, and multi-dideoxynucleoside-resistant infectious clones in vitro. Further development of these analogues as potential therapies for HIV-1 infection is warranted. JF - Antimicrobial Agents & Chemotherapy AU - Uchida, H AU - Kodama, EN AU - Yoshimura, K AU - Maeda, Y AU - Kosalaraksa, P AU - Maroun, V AU - Oiu, Y-L AU - Zemlicka, J AU - Mitsuya, H AD - Experimental Retrovirology Section, Medicine Branch, National Cancer Institute, Bldg. 10, Room 5A11, 9000 Rockville Pike, Bethesda, MD 20892, USA, hmitsuya@helix.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 1487 EP - 1490 VL - 43 IS - 6 SN - 0066-4804, 0066-4804 KW - E-methylenecyclopropane nucleoside KW - HIV-1 KW - MT-2 cells KW - Z-methylenecyclopropane nucleoside KW - human immunodeficiency virus 1 KW - man KW - methyl phenyl phosphoro-L-alaninate KW - methylenecyclopropane KW - nucleosides KW - zidovudine KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Drug resistance KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - V 22002:AIDS: Molecular and in vitro aspects KW - A 01068:Antiviral & viricidal KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17291584?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=In+vitro+anti-human+immunodeficiency+virus+activities+of+Z-+and+E-methylenecyclopropane+nucleoside+analogues+and+their+phosphoro-L-alaninate+diesters&rft.au=Uchida%2C+H%3BKodama%2C+EN%3BYoshimura%2C+K%3BMaeda%2C+Y%3BKosalaraksa%2C+P%3BMaroun%2C+V%3BOiu%2C+Y-L%3BZemlicka%2C+J%3BMitsuya%2C+H&rft.aulast=Uchida&rft.aufirst=H&rft.date=1999-06-01&rft.volume=43&rft.issue=6&rft.spage=1487&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Acquired immune deficiency syndrome; Drug resistance; Antiviral agents ER - TY - JOUR T1 - Carbon-13 Nuclear Magnetic Resonance Study of Metabolism of Propionate by Escherichia coli AN - 17287553; 4523480 AB - We have evaluated the use of [1,2- super(13)C sub(2)]propionate for the analysis of propionic acid metabolism, based on the ability to distinguish between the methylcitrate and methylmalonate pathways. Studies using propionate-adapted Escherichia coli MG1655 cells were performed. Preservation of the super(13)C- super(13)C- super(12)C carbon skeleton in labeled alanine and alanine-containing peptides involved in cell wall recycling is indicative of the direct formation of pyruvate from propionate via the methylcitrate cycle, the enzymes of which have recently been demonstrated in E. coli. Additionally, formation of super(13)C-labeled formate from pyruvate by the action of pyruvate-formate lyase is also consistent with the labeling of pyruvate C-1. Carboxylation of the labeled pyruvate leads to formation of [1,2- super(13)C sub(2)]oxaloacetate and to multiply labeled glutamate and succinate isotopomers, also consistent with the flux through the methylcitrate pathway, followed by the tricarboxylic acid (TCA) cycle. Additional labeling of TCA intermediates arises due to the formation of [1- super(13)C]acetyl coenzyme A from the labeled pyruvate formed via pyruvate-formate lyase. Labeling patterns in trehalose and glycine are also interpreted in terms of the above pathways. The information derived from the [1,2- super(13)C sub(2)]propionate label is contrasted with information which can be derived from singly or triply labeled propionate and shown to be more useful for distinguishing the different propionate utilization pathways via nuclear magnetic resonance analysis. JF - Journal of Bacteriology AU - London, R E AU - Allen, D L AU - Gabel, SA AU - DeRose, E F AD - MR-01 Laboratory of Structural Biology, National Institute of Environmental Health Sciences, Box 12233, Research Triangle Park, NC 27709, london@niehs.nih.gov++ Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 3562 EP - 3570 VL - 181 IS - 11 SN - 0021-9193, 0021-9193 KW - pathways KW - Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - N.M.R. KW - Propionic acid bacteria KW - Metabolism KW - J 02722:Biodegradation, growth, nutrition and leaching UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17287553?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Carbon-13+Nuclear+Magnetic+Resonance+Study+of+Metabolism+of+Propionate+by+Escherichia+coli&rft.au=London%2C+R+E%3BAllen%2C+D+L%3BGabel%2C+SA%3BDeRose%2C+E+F&rft.aulast=London&rft.aufirst=R&rft.date=1999-06-01&rft.volume=181&rft.issue=11&rft.spage=3562&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Propionic acid bacteria; N.M.R.; Metabolism ER - TY - JOUR T1 - Redundant In Vivo Proteolytic Activities of Escherichia coli Lon and the ClpYQ (HslUV) Protease AN - 17281567; 4534921 AB - The ClpYQ (HslUV) ATP-dependent protease of Escherichia coli consists of an ATPase subunit closely related to the Clp ATPases and a protease component related to those found in the eukaryotic proteasome. We found that this protease has a substrate specificity overlapping that of the Lon protease, another ATP-dependent protease in which a single subunit contains both the proteolytic active site and the ATPase. Lon is responsible for the degradation of the cell division inhibitor SulA; lon mutants are UV sensitive, due to the stabilization of SulA. lon mutants are also mucoid, due to the stabilization of another Lon substrate, the positive regulator of capsule transcription, RcsA. The overproduction of ClpYQ suppresses both of these phenotypes, and the suppression of UV sensitivity is accompanied by a restoration of the rapid degradation of SulA. Inactivation of the chromosomal copy of clpY or clpQ leads to further stabilization of SulA in a lon mutant but not in lon super(+) cells. While either lon, lon clpY, or lon clpQ mutants are UV sensitive at low temperatures, at elevated temperatures the lon mutant loses its UV sensitivity, while the double mutants do not. Therefore, the degradation of SulA by ClpYQ at elevated temperatures is sufficient to lead to UV resistance. Thus a protease with a structure and an active site different from those of Lon is capable of recognizing and degrading two different Lon substrates and appears to act as a backup for Lon under certain conditions. JF - Journal of Bacteriology AU - Wu, W AU - Zhou, Y AU - Gottesman, S AD - Bldg. 37, Rm. 2E18, National Cancer Institute, Bethesda, MD 20892-4255, susang@helix.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 3681 EP - 3687 VL - 181 IS - 12 SN - 0021-9193, 0021-9193 KW - ClpYQ protein KW - Lon proteinase KW - substrate specificity KW - Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - Endopeptidase La KW - Escherichia coli KW - Proteinase KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17281567?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Redundant+In+Vivo+Proteolytic+Activities+of+Escherichia+coli+Lon+and+the+ClpYQ+%28HslUV%29+Protease&rft.au=Wu%2C+W%3BZhou%2C+Y%3BGottesman%2C+S&rft.aulast=Wu&rft.aufirst=W&rft.date=1999-06-01&rft.volume=181&rft.issue=12&rft.spage=3681&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Proteolysis; Proteinase; Endopeptidase La ER - TY - JOUR T1 - The Mycobacterium marinum G13 promoter is a strong sigma 70-like promoter that is expressed in Escherichia coli and mycobacteria species AN - 17269998; 4569231 AB - A Mycobacterium marinum promoter, designated G13, was isolated from a promoter-trap library as a constitutive producer of the mutant green fluorescent protein. Sequence analysis, primer extension analysis, and computer promoter prediction analysis indicate that the G13 promoter is very similar to Escherichia coli consensus sigma super(70) promoters. Expression of the green fluorescent protein from the G13 promoter in M. marinum is, however, up to 40 times higher than that seen from the mycobacterial hsp60 promoter during exponential growth. Further, expression from this promoter does not appear to affect the growth of the organism in culture media or in macrophages. The strong expression of the G13 promoter allows it to be developed as a useful molecular tool for high level expression of markers in vitro. JF - FEMS Microbiology Letters AU - Barker, L P AU - Porcella, S F AU - Wyatt, R G AU - Small, PLC AD - Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Microscopy Branch, 903 South 4th St., Hamilton, MT 59840, USA Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 79 EP - 85 PB - Elsevier Science B.V. VL - 175 IS - 1 SN - 0378-1097, 0378-1097 KW - green fluorescent protein KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Promoters KW - Mycobacterium marinum KW - Escherichia coli KW - Media (culture) KW - N 14684:Expression of cloned genes KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17269998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=FEMS+Microbiology+Letters&rft.atitle=The+Mycobacterium+marinum+G13+promoter+is+a+strong+sigma+70-like+promoter+that+is+expressed+in+Escherichia+coli+and+mycobacteria+species&rft.au=Barker%2C+L+P%3BPorcella%2C+S+F%3BWyatt%2C+R+G%3BSmall%2C+PLC&rft.aulast=Barker&rft.aufirst=L&rft.date=1999-06-01&rft.volume=175&rft.issue=1&rft.spage=79&rft.isbn=&rft.btitle=&rft.title=FEMS+Microbiology+Letters&rft.issn=03781097&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mycobacterium marinum; Media (culture); Promoters ER - TY - JOUR T1 - Improving antibody affinity by mimicking somatic hypermutation in vitro AN - 17268881; 4571603 AB - In vivo affinity maturation of antibodies involves mutation of hot spots in the DNA encoding the variable regions. We have used this information to develop a strategy to improve antibody affinity in vitro using phage display technology. In our experiment with the antimesothelin scFv, SS(scFv), we identified DNA sequences in the variable regions that are naturally prone to hypermutations, selected a few hot spots encoding nonconserved amino acids, and introduced random mutations to make libraries with a size requirement between 10 super(3) and 10 super(4) independent clones. Panning of the hot spot libraries yielded several mutants with a 15- to 55-fold increase in affinity compared with a single clone with a fourfold increased affinity from a library in which mutagenesis was done outside the hot spots. The strategy should be generally applicable for the rapid isolation of higher-affinity mutants of Fvs, Fabs, and other recombinant antibodies from antibody phage libraries that are small in size. JF - Nature Biotechnology AU - Chowdhury, P S AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, Bethesda MD 20892-4255, USA, pasta@helix.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 568 EP - 572 VL - 17 IS - 6 SN - 1087-0156, 1087-0156 KW - Fv KW - somatic hypermutation KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Hot spots KW - Phage display KW - Peptide libraries KW - Antibodies KW - W3 33240:Immunology KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17268881?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Improving+antibody+affinity+by+mimicking+somatic+hypermutation+in+vitro&rft.au=Chowdhury%2C+P+S%3BPastan%2C+I&rft.aulast=Chowdhury&rft.aufirst=P&rft.date=1999-06-01&rft.volume=17&rft.issue=6&rft.spage=568&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Peptide libraries; Antibodies; Phage display; Hot spots ER - TY - JOUR T1 - Identification of Two New Proteins in Spermidine Nucleoids Isolated from Escherichia coli AN - 17249849; 4534914 AB - The Escherichia coli nucleoid contains DNA in a condensed but functional form. Analysis of proteins released from isolated spermidine nucleoids after treatment with DNase I reveals significant amounts of two proteins not previously detected in wild-type E. coli. Partial amino-terminal sequencing has identified them as the products of rdgC and yejK. These proteins are strongly conserved in gram-negative bacteria, suggesting that they have important cellular roles. JF - Journal of Bacteriology AU - Murphy, L D AU - Rosner, J L AU - Zimmerman, S B AU - Esposito, D AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 5, Room 328W, 5 Center Dr. MSC0560, Bethesda, MD 20892-0560, stevenz@bdg5.niddk.nih.gov Y1 - 1999/06// PY - 1999 DA - Jun 1999 SP - 3842 EP - 3844 VL - 181 IS - 12 SN - 0021-9193, 0021-9193 KW - nucleoids KW - rdgC gene KW - spermidine KW - yejK gene KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - N 14920:Chromatin & chromosomes KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17249849?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Identification+of+Two+New+Proteins+in+Spermidine+Nucleoids+Isolated+from+Escherichia+coli&rft.au=Murphy%2C+L+D%3BRosner%2C+J+L%3BZimmerman%2C+S+B%3BEsposito%2C+D&rft.aulast=Murphy&rft.aufirst=L&rft.date=1999-06-01&rft.volume=181&rft.issue=12&rft.spage=3842&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli ER - TY - JOUR T1 - Cell sensitivity to transplacental carcinogenesis by N-ethyl-N-nitrosourea is greatest in early post-implantation development AN - 17236182; 4522959 AB - In a clear demonstration of the changing sensitivity of the developing mammal to transplacental carcinogenesis, Ivankovic and Druckrey [S. Ivankovic, H. Druckrey, Transplacentare Erzeugung maligner Tumoren des Nervensystem: I. A thyl-nitroso-harnstoff ( A NH) an BD IX-Ratten, Z. Krebsforsch. 71 (1968) 320-360] exposed pregnant BD IX rats to a pulse of N-ethyl-N-nitrosourea (ENU), a reactive carcinogen with a half-life of 20 min. No tumors were seen with ENU exposure before gestation day 12, but the multiplicity of neurogenic tumors increased steadily thereafter and was greatest with treatment on day 20, followed by a decline in sensitivity for the last three days of gestation. Similarly, a transplacental study of ENU in the Syrian hamster [B.A. Diwan, S. Rehm, J.M. Rice, Age- and dose-dependent transplacental carcinogenesis by N-nitrosoethylurea in Syrian golden hamsters, J. Cancer Res. Clin. Oncol. 122 (1996) 643-652] found that the numbers of tumors induced were greatest after exposure of late fetal stages. While these observations suggested that embryonic cells are refractory to carcinogenesis, an alternative explanation could be that a significant tumor yield was not observed because too few target cells were present in the embryo. I have resolved this issue by combining these published data with others on the numbers of neuroectodermal cells in the developing BD IX rat brain [R. M u ller, M.F. Rajewsky, Elimination of O super(6)-ethylguanine from the DNA of brain, liver, and other rat tissues exposed to ethylnitrosourea at different stages of prenatal development, Cancer Res. 43 (1983) 2897-2904] and total cell counts of successive developmental stages of the Syrian hamster fetus [P.J. Donovan, G.T. Smith, Cell sensitivity to transplacental mutagenesis by N-ethyl-N-nitrosourea is greatest during early gestation in the Syrian hamster, Mutation Res., 1999, this issue], allowing the risk per cell at different stages of gestation to be calculated. Sensitivity to carcinogenesis was found to be greatest early in gestation and to decrease as gestation proceeds. For the rat model, tumor frequency per cell changed from 1.3 x 10 super(-6) at day 12 exposure to 2.6 x 10 super(-8) at day 23 exposure, a 50-fold decrease. For the hamster model, the tumor-initiation rate decreased 1250-fold from 1.2 x 10 super(-5) at day 7 exposure to 9.6 x 10 super(-9) at day 13 exposure. Thus, two independent experiments with different rodent species demonstrate that sensitivity of individual cells to damage leading to transplacental carcinogenesis is greatest in the early fetus and lessens markedly as gestation proceeds, in parallel with changing sensitivity to mutation (Donovan et al., Mutat. Res., this issue). JF - Mutation Research AU - Donovan, P J AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, USA Y1 - 1999/06/01/ PY - 1999 DA - 1999 Jun 01 SP - 59 EP - 63 PB - Elsevier Science B.V. VL - 427 IS - 1 SN - 0027-5107, 0027-5107 KW - brain KW - developmental satges KW - hamsters KW - implantation KW - liver KW - rats KW - Genetics Abstracts; Toxicology Abstracts KW - N-Ethyl-N-nitrosourea KW - Gestation KW - Carcinogenesis KW - Transplacental carcinogenesis KW - X 24200:Nitrosamines & related compounds KW - G 07221:Specific chemicals UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17236182?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mutation+Research&rft.atitle=Cell+sensitivity+to+transplacental+carcinogenesis+by+N-ethyl-N-nitrosourea+is+greatest+in+early+post-implantation+development&rft.au=Donovan%2C+P+J&rft.aulast=Donovan&rft.aufirst=P&rft.date=1999-06-01&rft.volume=427&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Mutation+Research&rft.issn=00275107&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenesis; N-Ethyl-N-nitrosourea; Transplacental carcinogenesis; Gestation ER - TY - JOUR T1 - Exposure assessment in community-based epidemiological studies. AN - 69800961; 10359403 JF - Lancet (London, England) AU - Stewart, P AD - Occupational Epidemiology Branch, National Cancer Institute, Rockville, MD 20892, USA. Y1 - 1999/05/29/ PY - 1999 DA - 1999 May 29 SP - 1816 EP - 1817 VL - 353 IS - 9167 SN - 0140-6736, 0140-6736 KW - Abridged Index Medicus KW - Index Medicus KW - Odds Ratio KW - Humans KW - Surveys and Questionnaires KW - Risk Assessment KW - Occupational Exposure KW - Occupational Diseases -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69800961?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Exposure+assessment+in+community-based+epidemiological+studies.&rft.au=Stewart%2C+P&rft.aulast=Stewart&rft.aufirst=P&rft.date=1999-05-29&rft.volume=353&rft.issue=9167&rft.spage=1816&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-24 N1 - Date created - 1999-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero. AN - 69826978; 10371172 AB - The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug in utero and becomes incorporated into newborn mouse DNA. This pilot study was designed to determine ZDV incorporation into human blood cell DNA from adults and newborn infants. In this prospective cohort study, peripheral blood mononuclear cells (PBMC) were obtained from 28 non-pregnant adults and 12 pregnant women given ZDV therapy, six non-pregnant adults with no exposure to ZDV, and six non-pregnant adults who last received ZDV > or = 6 months previously. In addition, cord blood leukocytes were obtained from 22 infants of HIV-1-positive, ZDV-exposed women and from 12 infants unexposed to ZDV. There were 11 mother-infant pairs involving HIV-1 -positive women. DNA was extracted from PBMC obtained from non-pregnant HIV-1-positive adults taking ZDV, pregnant HIV-1-positive women given ZDV during pregnancy, and from adults not taking ZDV. Cord blood leukocytes were examined from infants exposed to ZDV in utero and from unexposed controls. DNA samples were assayed for ZDV incorporation by anti-ZDV radioimmunoassay (RIA). The majority (76%) of samples from ZDV-exposed individuals, pregnant women (8 of 12), non-pregnant adults (24 of 28), or infants at delivery (15 of 22), had detectable ZDV-DNA levels. The range of positive values for ZDV-treated adults and infants was 25-544 and 22-452 molecules ZDV/10(6) nucleotides, respectively. Analysis of 11 mother-infant pairs showed variable ZDV-DNA incorporation in both, with no correlation by pair or by duration of drug treatment during pregnancy. Two of the 24 samples from individuals designated as controls were positive by anti-ZDV RIA. The 20-fold range for ZDV-DNA values in both adults and infants suggested large interindividual differences in ZDV phosphorylation. Incorporation of ZDV into DNA was detected in most of the samples from ZDV-exposed adults and infants. Therefore, the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be JF - AIDS (London, England) AU - Olivero, O A AU - Shearer, G M AU - Chougnet, C A AU - Kovacs, A A AU - Landay, A L AU - Baker, R AU - Stek, A M AU - Khoury, M M AU - Proia, L A AU - Kessler, H A AU - Sha, B E AU - Tarone, R E AU - Poirier, M C AD - Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/05/28/ PY - 1999 DA - 1999 May 28 SP - 919 EP - 925 VL - 13 IS - 8 SN - 0269-9370, 0269-9370 KW - Anti-HIV Agents KW - 0 KW - Zidovudine KW - 4B9XT59T7S KW - DNA KW - 9007-49-2 KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - Anti-HIV Agents -- therapeutic use KW - Anti-HIV Agents -- metabolism KW - Humans KW - Fetal Blood KW - Cohort Studies KW - Adult KW - Infant, Newborn KW - Anti-HIV Agents -- blood KW - Male KW - Female KW - Pregnancy KW - Zidovudine -- therapeutic use KW - Zidovudine -- metabolism KW - HIV Infections -- blood KW - DNA -- metabolism KW - DNA -- blood KW - Zidovudine -- blood KW - Leukocytes, Mononuclear -- metabolism KW - HIV Infections -- drug therapy KW - Pregnancy Complications, Infectious -- blood KW - Leukocytes, Mononuclear -- drug effects KW - Pregnancy Complications, Infectious -- drug therapy KW - HIV-1 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69826978?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=AIDS+%28London%2C+England%29&rft.atitle=Incorporation+of+zidovudine+into+leukocyte+DNA+from+HIV-1-positive+adults+and+pregnant+women%2C+and+cord+blood+from+infants+exposed+in+utero.&rft.au=Olivero%2C+O+A%3BShearer%2C+G+M%3BChougnet%2C+C+A%3BKovacs%2C+A+A%3BLanday%2C+A+L%3BBaker%2C+R%3BStek%2C+A+M%3BKhoury%2C+M+M%3BProia%2C+L+A%3BKessler%2C+H+A%3BSha%2C+B+E%3BTarone%2C+R+E%3BPoirier%2C+M+C&rft.aulast=Olivero&rft.aufirst=O&rft.date=1999-05-28&rft.volume=13&rft.issue=8&rft.spage=919&rft.isbn=&rft.btitle=&rft.title=AIDS+%28London%2C+England%29&rft.issn=02699370&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-02 N1 - Date created - 1999-09-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Can anomalous signal of sulfur become a tool for solving protein crystal structures? AN - 69781336; 10339407 AB - A general method for solving the phase problem from native crystals of macromolecules has long eluded structural biology. For well diffracting crystals this goal can now be achieved, as is shown here, thanks to modern data collection techniques and new statistical phasing algorithms. Using solely a native crystal of tetragonal hen egg-white lysozyme, a protein of 14 kDa molecular mass, it was possible to detect the positions of the ten sulfur and seven chlorine atoms from their anomalous signal, and proceed from there to obtain an electron-density map of very high quality. Copyright 1999 Academic Press. JF - Journal of molecular biology AU - Dauter, Z AU - Dauter, M AU - de La Fortelle, E AU - Bricogne, G AU - Sheldrick, G M AD - National Cancer Institute, Frederick and Brookhaven National Laboratory, Building 725A-X9, Upton, NY, 11973, USA. dauter@bnl.gov Y1 - 1999/05/28/ PY - 1999 DA - 1999 May 28 SP - 83 EP - 92 VL - 289 IS - 1 SN - 0022-2836, 0022-2836 KW - Chlorine KW - 4R7X1O2820 KW - Sulfur KW - 70FD1KFU70 KW - Muramidase KW - EC 3.2.1.17 KW - Index Medicus KW - Animals KW - Chickens KW - Chlorine -- analysis KW - Models, Molecular KW - Computer Graphics KW - Molecular Sequence Data KW - Algorithms KW - Amino Acid Sequence KW - Fourier Analysis KW - Molecular Weight KW - Sulfur -- chemistry KW - Crystallography, X-Ray -- methods KW - Muramidase -- chemistry KW - Protein Conformation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69781336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Can+anomalous+signal+of+sulfur+become+a+tool+for+solving+protein+crystal+structures%3F&rft.au=Dauter%2C+Z%3BDauter%2C+M%3Bde+La+Fortelle%2C+E%3BBricogne%2C+G%3BSheldrick%2C+G+M&rft.aulast=Dauter&rft.aufirst=Z&rft.date=1999-05-28&rft.volume=289&rft.issue=1&rft.spage=83&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-15 N1 - Date created - 1999-07-15 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - R1LZ8SF; PDB; 1LZ8 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytokine and immunoglobulin concentrations in cervical secretions: reproducibility of the Weck-cel collection instrument and correlates of immune measures AN - 17236346; 4522773 AB - Elucidation of local immune response at the cervix is important for understanding and evaluating STD vaccine approaches currently being proposed. However, no well-validated method exists for the collection of cervical secretions for evaluation of cervical immune response. The purpose of this study was to determine the reproducibility of the Weck-cel sponge used to collect cervical secretions for immunological assessment. Additionally, it was possible to examine correlates of immunity as part of our investigation. Two cervical secretion specimens were collected sequentially from each of 120 women using Weck-cel sponges. Cervical secretions were collected prior to Pap smear sampling to avoid blood contamination. At the laboratory, the duplicate specimens were weighed and tested in replicate wells to determine the concentration of two cytokines (IL-10 and IL-12) and two immunoglobulin isotypes (IgG and IgA). IL-12, total IgG, and total IgA showed a strong correlation between samples from the same woman ranging from 0.78 to 0.84. Kappa coefficients obtained after categorizing assay results ranged from 0.62 to 0.67. Variance components analysis suggested that 69% to 85% of the variance observed was accounted for by between-women variance, with the remaining variability attributed to variation between samples collected from the same woman. IL-10 results were less reproducible than those obtained from the other assays examined, suggesting problems with the assay used to measure this cytokine rather than with the Weck-cel sampling instrument. Various factors were found to significantly correlate with cytokine and immunoglobulin measures at the cervix. Age and reproductive status were associated with all four immune measures; women over 50 years of age and those who were postmenopausal had increased concentrations of IL-10, IL-12, IgG, and IgA. Hemoglobin concentrations were positively correlated with IgG and IL-10 concentrations, but not with IgA or IL-12 concentrations, suggesting local production of IgA and IL-12. The concentration of all immune measures decreased with increasing volume of collection. No significant association was observed between time from collection to freezing of specimens and concentrations of cytokines or immunoglobulins. Overall, our data suggest that measurement of immunological parameters in cervical secretions collected using Weck-cel sponges are reproducible. In addition, various correlates of cytokine and immunoglobulin concentrations were identified. JF - Journal of Immunological Methods AU - Hildesheim, A AU - McShane, L M AU - Schiffman, M AU - Bratti, M C AU - Rodriguez, A C AU - Herrero, R AU - Morera, LA AU - Cardenas, F AU - Saxon, L AU - Bowman, F P AU - Crowley-Nowick, P A AD - Interdisciplinary Studies Section, Environmental Epidemiology Branch, DCEG, National Cancer Institute, 6130 Executive Blvd, EPN 443, Bethesda, MD 20892-7374, USA Y1 - 1999/05/27/ PY - 1999 DA - 1999 May 27 SP - 131 EP - 143 PB - Elsevier Science B.V. VL - 225 IS - 1-2 SN - 0022-1759, 0022-1759 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Mucosa KW - Interleukin 10 KW - Interleukin 12 KW - Immunoglobulin A KW - Immunoglobulin G KW - Cytokines KW - Cervix KW - F 06731:Other methods KW - W 30965:Miscellaneous, Reviews KW - W3 33250:Methods: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17236346?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunological+Methods&rft.atitle=Cytokine+and+immunoglobulin+concentrations+in+cervical+secretions%3A+reproducibility+of+the+Weck-cel+collection+instrument+and+correlates+of+immune+measures&rft.au=Hildesheim%2C+A%3BMcShane%2C+L+M%3BSchiffman%2C+M%3BBratti%2C+M+C%3BRodriguez%2C+A+C%3BHerrero%2C+R%3BMorera%2C+LA%3BCardenas%2C+F%3BSaxon%2C+L%3BBowman%2C+F+P%3BCrowley-Nowick%2C+P+A&rft.aulast=Hildesheim&rft.aufirst=A&rft.date=1999-05-27&rft.volume=225&rft.issue=1-2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunological+Methods&rft.issn=00221759&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immunoglobulin G; Mucosa; Immunoglobulin A; Cytokines; Interleukin 10; Cervix; Interleukin 12 ER - TY - JOUR T1 - Substrate sequestration by a proteolytically inactive Lon mutant. AN - 69775260; 10339542 AB - Lon protein of Escherichia coli is an ATP-dependent protease responsible for the rapid turnover of both abnormal and naturally unstable proteins, including SulA, a cell division inhibitor made after DNA damage, and RcsA, a positive regulator of transcription. Lon is a multimer of identical 94-kDa subunits, each containing a consensus ATPase motif and a serine active site. We found that overexpressing Lon, which is mutated for the serine active site (LonS679A) and is therefore devoid of proteolytic activity, unexpectedly led to complementation of the UV sensitivity and capsule overproduction of a lon deletion mutant. SulA was not degraded by LonS679A, but rather was completely protected by the Lon mutant from degradation by other cellular proteases. We interpret these results to mean that the mutant LonS679A binds but does not degrade Lon substrates, resulting in sequestration of the substrate proteins and interference with their activities, resulting in apparent complementation. Lon that carried a mutation in the consensus ATPase site, either with or without the active site serine, was no longer able to complement a Deltalon mutant. These in vivo results suggest that the pathway of degradation by Lon couples ATP-dependent unfolding with movement of the substrate into protected chambers within Lon, where it is held until degradation proceeds. In the absence of degradation the substrate remains sequestered. Comparison of our results with those from a number of other systems suggest that proteins related to the regulatory portions of energy-dependent proteases act as energy-dependent sequestration proteins. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Van Melderen, L AU - Gottesman, S AD - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA. Y1 - 1999/05/25/ PY - 1999 DA - 1999 May 25 SP - 6064 EP - 6071 VL - 96 IS - 11 SN - 0027-8424, 0027-8424 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - Heat-Shock Proteins KW - Recombinant Proteins KW - sulA protein, E coli KW - Serine KW - 452VLY9402 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Arabinose KW - B40ROO395Z KW - ATP-Dependent Proteases KW - EC 3.4.21.- KW - Serine Endopeptidases KW - Lon protein, E coli KW - EC 3.4.21.53 KW - Protease La KW - Adenosine Triphosphatases KW - EC 3.6.1.- KW - Index Medicus KW - Ultraviolet Rays KW - Recombinant Proteins -- biosynthesis KW - Bacterial Proteins -- metabolism KW - Amino Acid Sequence KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Arabinose -- metabolism KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Adenosine Triphosphate -- metabolism KW - Models, Chemical KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Consensus Sequence KW - Amino Acid Substitution KW - Cell Division KW - Heat-Shock Proteins -- metabolism KW - Serine Endopeptidases -- metabolism KW - Serine Endopeptidases -- genetics KW - Serine Endopeptidases -- chemistry KW - Adenosine Triphosphatases -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology KW - Heat-Shock Proteins -- genetics KW - Heat-Shock Proteins -- chemistry KW - Escherichia coli -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69775260?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Substrate+sequestration+by+a+proteolytically+inactive+Lon+mutant.&rft.au=Van+Melderen%2C+L%3BGottesman%2C+S&rft.aulast=Van+Melderen&rft.aufirst=L&rft.date=1999-05-25&rft.volume=96&rft.issue=11&rft.spage=6064&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-24 N1 - Date created - 1999-06-24 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1981 Aug;78(8):4931-5 [6458037] Proc Natl Acad Sci U S A. 1981 Aug;78(8):4728-32 [6458036] J Bacteriol. 1983 Jun;154(3):1339-46 [6343351] Proc Natl Acad Sci U S A. 1984 Jul;81(14):4490-4 [6087326] Science. 1995 Jul 28;269(5223):496-512 [7542800] Genes Dev. 1995 Oct 1;9(19):2399-408 [7557391] J Bacteriol. 1996 Jun;178(12):3440-6 [8655539] Genes Dev. 1996 Jun 15;10(12):1532-42 [8666236] Science. 1996 Oct 4;274(5284):103-6 [8810243] J Biol Chem. 1996 Nov 1;271(44):27730-8 [8910366] J Biol Chem. 1996 Nov 29;271(48):30798-803 [8940060] J Bacteriol. 1997 Jan;179(1):107-14 [8981986] Annu Rev Genet. 1996;30:465-506 [8982462] Genes Dev. 1997 Jan 1;11(1):119-28 [9000055] Trends Biochem Sci. 1997 Oct;22(10):399-404 [9357316] Proc Natl Acad Sci U S A. 1985 Sep;82(18):6045-9 [2994059] J Bacteriol. 1985 Dec;164(3):1124-35 [2999072] J Bacteriol. 1986 Jun;166(3):733-8 [3011740] J Bacteriol. 1987 Mar;169(3):981-9 [3029041] J Biol Chem. 1987 Apr 5;262(10):4508-15 [3549709] J Bacteriol. 1988 Jun;170(6):2599-611 [2836365] J Biol Chem. 1988 Jun 25;263(18):8727-34 [2967816] J Biol Chem. 1990 May 15;265(14):7886-93 [2186030] J Biol Chem. 1990 Jul 25;265(21):12546-52 [2197276] J Bacteriol. 1990 Oct;172(10):5602-9 [2145263] J Bacteriol. 1990 Dec;172(12):7297-300 [2254289] J Bacteriol. 1991 Mar;173(5):1738-47 [1999391] FEBS Lett. 1991 Aug 5;287(1-2):211-4 [1652461] Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1053-7 [8430073] J Bacteriol. 1993 Apr;175(8):2271-7 [8468287] J Bacteriol. 1993 Jul;175(14):4538-44 [8331082] J Bacteriol. 1993 Jul;175(14):4545-9 [8331083] J Biol Chem. 1993 Oct 25;268(30):22502-7 [8226758] J Biol Chem. 1993 Oct 25;268(30):22609-17 [8226769] J Biol Chem. 1993 Oct 25;268(30):22618-26 [8226770] Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11247-51 [8248235] J Biol Chem. 1994 Jan 7;269(1):238-42 [8276800] Science. 1994 Apr 8;264(5156):273-6 [8146662] J Bacteriol. 1994 Nov;176(21):6518-27 [7961402] FEBS Lett. 1994 Dec 12;356(1):101-3 [7988699] Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12218-22 [7991609] EMBO J. 1995 May 1;14(9):1867-77 [7743994] Cell. 1997 Nov 14;91(4):447-56 [9390554] Biochemistry. 1998 Jan 6;37(1):377-86 [9425059] FEBS Lett. 1998 Jan 30;422(2):218-20 [9490010] J Bacteriol. 1998 Mar;180(5):1154-8 [9495753] Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2885-90 [9501185] Bioorg Khim. 1998 Apr;24(4):293-9 [9612572] Plant Mol Biol. 1998 May;37(1):141-54 [9620272] Mol Cell. 1998 Jan;1(2):265-75 [9659923] Trends Cell Biol. 1998 Feb;8(2):65-71 [9695811] Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12135-40 [9770452] J Bacteriol. 1995 Jul;177(14):4121-30 [7608087] Cell. 1981 Apr;24(1):225-33 [6453650] Proc Natl Acad Sci U S A. 1983 Jan;80(2):358-62 [6300834] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status AN - 17238034; 4523335 AB - The Escherichia coli transcription factor OxyR is activated by the formation of an intramolecular disulfide bond and subsequently is deactivated by enzymatic reduction of the disulfide bond. Here we show that OxyR can be activated by two possible pathways. In mutants defective in the cellular disulfide- reducing systems, OxyR is constitutively activated by a change in the thiol---disulfide redox status in the absence of added oxidants. In wild- type cells, OxyR is activated by hydrogen peroxide. By monitoring the presence of the OxyR disulfide bond after exposure to hydrogen peroxide in vivo and in vitro, we also show that the kinetics of OxyR oxidation by low concentrations of hydrogen peroxide is significantly faster than the kinetics of OxyR reduction, allowing for transient activation in an overall reducing environment. We propose that the activity of OxyR in vivo is determined by the balance between hydrogen peroxide levels and the cellular redox environment. JF - Proceedings of the National Academy of Sciences, USA AU - Aaslund, F AU - Zheng, M AU - Beckwith, J AU - Storz, G AD - Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, storz@helix.nih.gov Y1 - 1999/05/25/ PY - 1999 DA - 1999 May 25 SP - 6161 EP - 6165 VL - 96 IS - 11 SN - 0027-8424, 0027-8424 KW - OxyR protein KW - hydrogen peroxide KW - redox environment KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Escherichia coli KW - J 02726:RNA and ribosomes KW - N 14930:Transcription factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17238034?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Regulation+of+the+OxyR+transcription+factor+by+hydrogen+peroxide+and+the+cellular+thiol-disulfide+status&rft.au=Aaslund%2C+F%3BZheng%2C+M%3BBeckwith%2C+J%3BStorz%2C+G&rft.aulast=Aaslund&rft.aufirst=F&rft.date=1999-05-25&rft.volume=96&rft.issue=11&rft.spage=6161&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli ER - TY - JOUR T1 - The role of amino acids in extracellular loops of the human P2Y1 receptor in surface expression and activation processes. AN - 69756620; 10329657 AB - The P2Y1 receptor is a membrane-bound G protein-coupled receptor stimulated by adenine nucleotides. Using alanine scanning mutagenesis, the role in receptor activation of charged amino acids (Asp, Glu, Lys, and Arg) and cysteines in the extracellular loops (EL) of the human P2Y1 receptor has been investigated. The mutant receptors were expressed in COS-7 cells and measured for stimulation of phospholipase C induced by the potent agonist 2-methylthioadenosine-5'-diphosphate (2-MeSADP). In addition to single point mutations, all receptors carried the hemagglutinin epitope at the N- terminus for detection of cell-surface expression. The C124A and C202A mutations, located near the exofacial end of transmembrane helix 3 and in EL2, respectively, ablated phospholipase C stimulation by 1000-fold greater than for the wild-type receptor. The double mutant receptor C42A/C296A exhibited no additive shift in the concentration-response curve for 2-MeSADP. These data suggest that Cys42 and Cys296 form another disulfide bridge in the extracellular region, which is critical for activation. Replacement of charged amino acids produced only minor changes in receptor activation, with two remarkable exceptions. The E209A mutant receptor (EL2) exhibited a >1000-fold shift in EC50. However, if Glu209 were substituted with amino acids capable of hydrogen bonding (Asp, Gln, or Arg), the mutant receptors responded like the wild-type receptor. Arg287 in EL3 was impaired similarly to Glu209 when substituted by alanine. Substitution of Arg287 by lysine, another positively charged residue, failed to fully restore wild-type activity. JF - The Journal of biological chemistry AU - Hoffmann, C AU - Moro, S AU - Nicholas, R A AU - Harden, T K AU - Jacobson, K A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/05/21/ PY - 1999 DA - 1999 May 21 SP - 14639 EP - 14647 VL - 274 IS - 21 SN - 0021-9258, 0021-9258 KW - Amino Acids KW - 0 KW - P2RY1 protein, human KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - Cysteine KW - K848JZ4886 KW - Index Medicus KW - Humans KW - Cysteine -- genetics KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Cell Membrane -- physiology KW - Protein Structure, Tertiary KW - Mutation KW - Receptors, Purinergic P2 -- chemistry KW - Amino Acids -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69756620?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+role+of+amino+acids+in+extracellular+loops+of+the+human+P2Y1+receptor+in+surface+expression+and+activation+processes.&rft.au=Hoffmann%2C+C%3BMoro%2C+S%3BNicholas%2C+R+A%3BHarden%2C+T+K%3BJacobson%2C+K+A&rft.aulast=Hoffmann&rft.aufirst=C&rft.date=1999-05-21&rft.volume=274&rft.issue=21&rft.spage=14639&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-09 N1 - Date created - 1999-07-09 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Br J Pharmacol. 1997 May;121(2):338-44 [9154346] J Biol Chem. 1997 Jul 11;272(28):17405-9 [9211882] J Hypertens. 1997 Jul;15(7):703-14 [9222937] Neurochem Res. 1997 Aug;22(8):1023-31 [9239758] Mol Pharmacol. 1997 Sep;52(3):499-507 [9281613] Biochemistry. 1997 Dec 16;36(50):15670-6 [9398295] J Med Chem. 1998 Jan 15;41(2):183-90 [9457242] Biochem J. 1988 Jun 1;252(2):583-93 [2843174] Regul Pept. 1997 Oct 31;72(2-3):97-103 [9652982] J Med Chem. 1998 Apr 23;41(9):1456-66 [9554879] Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8070-4 [9653141] Mol Pharmacol. 1998 Aug;54(2):364-71 [9687578] J Biol Chem. 1999 Jan 15;274(3):1349-58 [9880506] Biochemistry. 1999 Mar 23;38(12):3498-507 [10090736] Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 [271968] Biochem J. 1983 May 15;212(2):473-82 [6309146] Methods Enzymol. 1987;152:684-704 [3657593] J Med Chem. 1993 Nov 26;36(24):3937-46 [8254622] J Biol Chem. 1994 Jan 28;269(4):2863-9 [8300621] Mol Pharmacol. 1994 Apr;45(4):690-5 [8183248] Biochem Biophys Res Commun. 1994 Jun 15;201(2):523-30 [8002982] J Biol Chem. 1994 Jul 29;269(30):19343-8 [8034699] J Biol Chem. 1994 Oct 7;269(40):24692-8 [7929142] Pharmacol Rev. 1994 Jun;46(2):143-56 [7938164] J Biol Chem. 1994 Dec 9;269(49):30953-9 [7983030] J Biol Chem. 1995 Mar 3;270(9):4185-8 [7876172] Pharmacol Ther. 1994;64(3):445-75 [7724657] J Biol Chem. 1995 May 26;270(21):12846-50 [7759541] Regul Pept. 1995 May 30;57(2):141-7 [7659790] J Biol Chem. 1995 Sep 15;270(37):21619-25 [7665575] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11642-6 [8524820] J Biol Chem. 1996 Jan 12;271(2):702-6 [8557676] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):433-7 [8552654] Mol Pharmacol. 1996 Apr;49(4):683-91 [8609897] Biochem Pharmacol. 1996 Feb 23;51(4):545-55 [8619901] Mol Endocrinol. 1995 Dec;9(12):1708-19 [8614407] Endocrinology. 1996 Jul;137(7):2851-8 [8770906] Br J Pharmacol. 1996 Aug;118(8):1959-64 [8864529] Drug Des Discov. 1995 Nov;13(2):133-54 [8872457] Mol Pharmacol. 1996 Nov;50(5):1118-26 [8913343] FEBS Lett. 1997 Feb 3;402(2-3):203-8 [9037196] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synaptophysin is phosphorylated in rat cortical synaptosomes treated with botulinum toxin A AN - 17303837; 4562509 AB - Phosphorylation and dephosphorylation of neuronal proteins have been implicated in regulation of synaptic transmission. Studies were performed to determine if synaptophysin was phosphorylated or dephosphorylated during exposure of synaptosomes to botulinum toxin A (BoTX/A). Cholinergic-enriched synaptosomes were preincubated in the presence of super(3)H-choline to label newly synthesized acetylcholine ( super(3)H-ACh). This was followed by incubation with low or high potassium to stimulate release of newly synthesized super(3)H-ACh. BoTX/A inhibited total Ach release by 15-19% and inhibited release of newly synthesized super(3)H-ACh by 35%. A 165% increase in synaptophysin phosphorylation occurred in a dose-dependent manner over a range of doses (0.2 nM, 2 nM, 20 nM, 100 nM) of BoTX/A. When 4-Aminopyridine was added to synaptosomes that were BoTX/A treated, synaptophysin was dephosphorylated to control levels. Synaptosomes incubated with BoTX/A exhibited an inhibition of potassium stimulated ACh release and an increase in synaptophysin phosphorylation. Synaptophysin phosphorylation may be involved in inhibition of acetylcholine release. JF - Life Sciences AU - Asermely, KE AU - Sterling, G H AU - McCafferty, M R AU - O'Neill, J J AD - National Institutes of Health, National Institute of Neurological Disorders and Stroke, Building 36/Room 5D-06 36 Convent Drive Bethesda, MD 20892, asermely@codon.nih.gov Y1 - 1999/05/21/ PY - 1999 DA - 1999 May 21 SP - 297 EP - 303 VL - 64 IS - 26 SN - 0024-3205, 0024-3205 KW - Toxin A KW - botulinum neurotoxin KW - botulinum toxin KW - rats KW - synaptophysin KW - toxin A KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts; CSA Neurosciences Abstracts KW - Synaptosomes KW - Clostridium botulinum KW - Cortex KW - Phosphorylation KW - Acetylcholine KW - N3 11104:Mammals (except primates) KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17303837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Life+Sciences&rft.atitle=Synaptophysin+is+phosphorylated+in+rat+cortical+synaptosomes+treated+with+botulinum+toxin+A&rft.au=Asermely%2C+KE%3BSterling%2C+G+H%3BMcCafferty%2C+M+R%3BO%27Neill%2C+J+J&rft.aulast=Asermely&rft.aufirst=KE&rft.date=1999-05-21&rft.volume=64&rft.issue=26&rft.spage=297&rft.isbn=&rft.btitle=&rft.title=Life+Sciences&rft.issn=00243205&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Clostridium botulinum; Cortex; Toxin A; Phosphorylation; Acetylcholine; Synaptosomes ER - TY - JOUR T1 - Nickel(II) acetate-treated Chinese hamster ovary cells differentially express Vimentin, hSNF2H homologue, and H ferritin. AN - 69763982; 10329430 AB - In probing the possible non-genotoxic molecular mechanism(s) of nickel(II)-induced carcinogenesis, we performed a non-radioactive mRNA differential display analysis for nickel(II) acetate-treated Chinese hamster ovary cells (CHO-K1-BH4). Three out of thirty differentially expressed cDNAs had sequences highly similar to known genes. Down-regulation of vimentin and a hSNF2H homologue and up-regulation of ferritin heavy chain were confirmed by Northern blot analysis. The expression of these mRNAs was time- and nickel(II) concentration-dependent. For vimentin, the decrease in mRNA level was concurrent with a decrease in the protein level. For ferritin, the increase in mRNA had no effect on the protein level. Dysregulation of these gene products signifies their involvement in the epigenetic effects of carcinogenic nickel(II) compounds. JF - Biochemical and biophysical research communications AU - Lee, S H AU - Shiao, Y H AU - Plisov, S Y AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland, 21702, USA. Y1 - 1999/05/19/ PY - 1999 DA - 1999 May 19 SP - 592 EP - 595 VL - 258 IS - 3 SN - 0006-291X, 0006-291X KW - Acetates KW - 0 KW - DNA Primers KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Organometallic Compounds KW - RNA, Messenger KW - Transcription Factors KW - Vimentin KW - nickel acetate KW - 373-02-4 KW - Ferritins KW - 9007-73-2 KW - Index Medicus KW - Animals KW - Base Sequence KW - Cricetulus KW - CHO Cells KW - RNA, Messenger -- genetics KW - Cricetinae KW - Cloning, Molecular KW - Organometallic Compounds -- pharmacology KW - Ferritins -- genetics KW - DNA-Binding Proteins -- genetics KW - Transcription Factors -- genetics KW - Vimentin -- genetics KW - Acetates -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69763982?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Nickel%28II%29+acetate-treated+Chinese+hamster+ovary+cells+differentially+express+Vimentin%2C+hSNF2H+homologue%2C+and+H+ferritin.&rft.au=Lee%2C+S+H%3BShiao%2C+Y+H%3BPlisov%2C+S+Y%3BKasprzak%2C+K+S&rft.aulast=Lee&rft.aufirst=S&rft.date=1999-05-19&rft.volume=258&rft.issue=3&rft.spage=592&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-24 N1 - Date created - 1999-06-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EXO1 of Saccharomyces cerevisiae functions in mutagenesis during double-strand break repair. AN - 69903368; 10415501 JF - Annals of the New York Academy of Sciences AU - Holbeck, S L AU - Strathern, J N AD - NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Maryland 21702-1201, USA. Y1 - 1999/05/18/ PY - 1999 DA - 1999 May 18 SP - 375 EP - 377 VL - 870 SN - 0077-8923, 0077-8923 KW - DNA, Fungal KW - 0 KW - Exodeoxyribonucleases KW - EC 3.1.- KW - exodeoxyribonuclease I KW - EC 3.1.11.1 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - DNA Repair KW - Exodeoxyribonucleases -- physiology KW - Saccharomyces cerevisiae -- enzymology KW - Exodeoxyribonucleases -- genetics KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69903368?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Annals+of+the+New+York+Academy+of+Sciences&rft.atitle=EXO1+of+Saccharomyces+cerevisiae+functions+in+mutagenesis+during+double-strand+break+repair.&rft.au=Holbeck%2C+S+L%3BStrathern%2C+J+N&rft.aulast=Holbeck&rft.aufirst=S&rft.date=1999-05-18&rft.volume=870&rft.issue=&rft.spage=375&rft.isbn=&rft.btitle=&rft.title=Annals+of+the+New+York+Academy+of+Sciences&rft.issn=00778923&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-19 N1 - Date created - 1999-08-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A single amino acid residue contributes to distinct mechanisms of inhibition of the human multidrug transporter by stereoisomers of the dopamine receptor antagonist flupentixol. AN - 69792628; 10350482 AB - Both cis and trans isomers of the dopamine receptor antagonist flupentixol inhibit drug transport and reverse drug resistance mediated by the human multidrug transporter P-glycoprotein (Pgp) with a stereoselective potency. The rate of ATP hydrolysis by Pgp and photoaffinity labeling of Pgp with the substrate analogue [125I]iodoarylazidoprazosin ([125I]IAAP) are modulated by each isomer in an opposite manner, suggesting different mechanisms for the inhibitory effect on drug transport. In this study we demonstrate that substitution of a single phenylalanine residue at position 983 (F983) with alanine (F983A) in putative transmembrane (TM) region 12 selectively affects inhibition of Pgp-mediated drug transport by both isomers of flupentixol. In F983A the stimulatory effect of cis(Z)-flupentixol and the inhibitory effect of trans(E)-flupentixol on ATP hydrolysis and [125I]IAAP labeling were significantly altered. This indicates that F983 contributes to inhibition of drug transport by both isomers of flupentixol and plays an important role in stimulation and inhibition of ATP hydrolysis and [125I]IAAP labeling by cis(Z)- and trans(E)-flupentixol, respectively. The near-wild-type level of drug transport by the F983A Pgp mutant dissociates susceptibility to inhibition by flupentixol from drug translocation, indicating the allosteric nature of the flupentixol interaction. The inhibitory effects of cyclosporin A on drug transport, drug-stimulated ATP hydrolysis, and [125I]IAAP labeling as well as the stimulatory effect of verapamil on ATP hydrolysis by Pgp were minimally affected by substitution of F983, suggesting no global alteration in the structural and functional integrity of the mutant. Taken together, our data suggest that distinct mechanisms of inhibition of Pgp-mediated drug transport by the cis and trans isomers of flupentixol are mediated through a common site of interaction. JF - Biochemistry AU - Dey, S AU - Hafkemeyer, P AU - Pastan, I AU - Gottesman, M M AD - Laboratory of Cell Biology, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/05/18/ PY - 1999 DA - 1999 May 18 SP - 6630 EP - 6639 VL - 38 IS - 20 SN - 0006-2960, 0006-2960 KW - Azides KW - 0 KW - Dopamine Antagonists KW - Iodine Radioisotopes KW - P-Glycoprotein KW - Photoaffinity Labels KW - Receptors, Dopamine KW - Phenylalanine KW - 47E5O17Y3R KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - azidoprazosin KW - 90990-97-9 KW - Verapamil KW - CJ0O37KU29 KW - Flupenthixol KW - FA0UYH6QUO KW - Alanine KW - OF5P57N2ZX KW - Prazosin KW - XM03YJ541D KW - Index Medicus KW - Substrate Specificity -- drug effects KW - Prazosin -- metabolism KW - Stereoisomerism KW - Prazosin -- analogs & derivatives KW - HeLa Cells KW - Humans KW - Biological Transport -- genetics KW - Verapamil -- pharmacology KW - Azides -- antagonists & inhibitors KW - Biological Transport -- drug effects KW - Mutagenesis, Site-Directed KW - Prazosin -- antagonists & inhibitors KW - Azides -- metabolism KW - Photoaffinity Labels -- metabolism KW - Tumor Cells, Cultured KW - Amino Acid Substitution -- genetics KW - Adenosine Triphosphate -- metabolism KW - Alanine -- genetics KW - Hydrolysis -- drug effects KW - Iodine Radioisotopes -- metabolism KW - Receptors, Dopamine -- metabolism KW - Phenylalanine -- physiology KW - Dopamine Antagonists -- chemistry KW - P-Glycoprotein -- genetics KW - Flupenthixol -- pharmacology KW - Dopamine Antagonists -- pharmacology KW - Phenylalanine -- genetics KW - Flupenthixol -- chemistry KW - P-Glycoprotein -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69792628?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=A+single+amino+acid+residue+contributes+to+distinct+mechanisms+of+inhibition+of+the+human+multidrug+transporter+by+stereoisomers+of+the+dopamine+receptor+antagonist+flupentixol.&rft.au=Dey%2C+S%3BHafkemeyer%2C+P%3BPastan%2C+I%3BGottesman%2C+M+M&rft.aulast=Dey&rft.aufirst=S&rft.date=1999-05-18&rft.volume=38&rft.issue=20&rft.spage=6630&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-09 N1 - Date created - 1999-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A role for neutral sphingomyelinase-mediated ceramide production in T cell receptor-induced apoptosis and mitogen-activated protein kinase-mediated signal transduction. AN - 69761027; 10330437 AB - Studying apoptosis induced by T cell receptor (TCR) cross-linking in the T cell hybridoma, 3DO, we found both neutral sphingomyelinase activation and production of ceramide upon receptor engagement. Pharmacological inhibition of ceramide production by the fungal toxin, fumonisin B1, impaired TCR-induced interleukin (IL)-2 production and programmed cell death. Addition of either exogenous ceramide or bacterial sphingomyelinase reconstituted both responses. Moreover, specific inactivation of neutral sphingomyelinase by antisense RNA inhibited IL-2 production and mitogen-activated protein kinase activation after TCR triggering. These results suggest that ceramide production by activation of neutral sphingomyelinase is an essential component of the TCR signaling machinery. JF - The Journal of experimental medicine AU - Tonnetti, L AU - Verí, M C AU - Bonvini, E AU - D'Adamio, L AD - T-Cell Apoptosis Unit, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/05/17/ PY - 1999 DA - 1999 May 17 SP - 1581 EP - 1589 VL - 189 IS - 10 SN - 0022-1007, 0022-1007 KW - Carboxylic Acids KW - 0 KW - Ceramides KW - FASLG protein, human KW - Fas Ligand Protein KW - Fasl protein, mouse KW - Fumonisins KW - Interleukin-2 KW - Membrane Glycoproteins KW - Mycotoxins KW - RNA, Antisense KW - RNA, Messenger KW - Receptors, Antigen, T-Cell KW - Sphingomyelins KW - fumonisin B1 KW - 3ZZM97XZ32 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Sphingomyelin Phosphodiesterase KW - EC 3.1.4.12 KW - Index Medicus KW - Animals KW - Mycotoxins -- pharmacology KW - Interleukin-2 -- metabolism KW - Enzyme Activation KW - Humans KW - Jurkat Cells KW - Hybridomas -- immunology KW - Mice KW - RNA, Messenger -- genetics KW - Mice, Inbred BALB C KW - Sphingomyelins -- metabolism KW - Second Messenger Systems -- immunology KW - Hybridomas -- enzymology KW - Carboxylic Acids -- pharmacology KW - Spleen -- immunology KW - RNA, Antisense -- pharmacology KW - Membrane Glycoproteins -- immunology KW - Signal Transduction KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Apoptosis KW - Receptors, Antigen, T-Cell -- antagonists & inhibitors KW - Calcium-Calmodulin-Dependent Protein Kinases -- antagonists & inhibitors KW - Sphingomyelin Phosphodiesterase -- metabolism KW - Ceramides -- metabolism KW - Receptors, Antigen, T-Cell -- immunology KW - T-Lymphocytes -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69761027?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=A+role+for+neutral+sphingomyelinase-mediated+ceramide+production+in+T+cell+receptor-induced+apoptosis+and+mitogen-activated+protein+kinase-mediated+signal+transduction.&rft.au=Tonnetti%2C+L%3BVer%C3%AD%2C+M+C%3BBonvini%2C+E%3BD%27Adamio%2C+L&rft.aulast=Tonnetti&rft.aufirst=L&rft.date=1999-05-17&rft.volume=189&rft.issue=10&rft.spage=1581&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-10 N1 - Date created - 1999-06-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1996 Dec 13;274(5294):1855-9 [8943189] Immunity. 1996 Sep;5(3):197-205 [8808675] Annu Rev Immunol. 1997;15:707-47 [9143705] J Biol Chem. 1997 Aug 22;272(34):21625-34 [9261185] EMBO J. 1997 Oct 15;16(20):6200-8 [9321399] Curr Opin Struct Biol. 1997 Dec;7(6):839-48 [9434905] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3638-43 [9520418] J Immunol. 1998 Feb 1;160(3):1059-66 [9570517] J Immunol. 1981 Dec;127(6):2488-95 [6170707] Cell. 1987 Apr 24;49(2):273-80 [3494522] Nature. 1988 Mar 3;332(6159):35-40 [3126396] Nature. 1988 Mar 3;332(6159):40-5 [3126397] Nature. 1988 Jun 23;333(6175):742-6 [3260350] Nature. 1988 Nov 3;336(6194):73-6 [3263574] Nature. 1988 Nov 24;336(6197):388-90 [3264053] Nature. 1988 Dec 1;336(6198):471-3 [3264054] Nature. 1989 Jan 12;337(6203):181-4 [2521375] Science. 1989 Apr 14;244(4901):214-7 [2784868] Nature. 1989 Aug 17;340(6234):559-62 [2528070] J Exp Med. 1990 Oct 1;172(4):1065-70 [1976734] Science. 1990 Nov 30;250(4985):1253-6 [1700866] Cell. 1990 Dec 21;63(6):1249-56 [2148123] Nature. 1991 Jan 17;349(6306):245-8 [1670963] Science. 1990 Dec 21;250(4988):1720-3 [2125367] J Immunol. 1991 May 15;146(10):3340-6 [1827483] J Immunol Methods. 1991 Jun 3;139(2):271-9 [1710634] Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453-6 [1828897] Nature. 1991 Oct 31;353(6347):858-61 [1944559] Nature. 1992 Apr 16;356(6370):607-9 [1313950] Ciba Found Symp. 1992;164:208-18; discussion 218-22 [1395932] J Immunol. 1992 Dec 1;149(11):3550-3 [1331238] Science. 1993 Jan 22;259(5094):519-22 [8424175] Eur J Immunol. 1993 Mar;23(3):747-53 [8095461] Cell. 1993 Apr 23;73(2):209-12 [8477442] J Biol Chem. 1993 Jul 5;268(19):14476-81 [8314804] J Biol Chem. 1994 Jan 28;269(4):3047-52 [8300638] Nature. 1994 Jan 20;367(6460):277-81 [8121493] Nature. 1994 Jan 20;367(6460):281-4 [8121494] Nature. 1995 Feb 2;373(6513):438-41 [7530335] Nature. 1995 Feb 2;373(6513):441-4 [7530336] Nature. 1995 Feb 2;373(6513):444-8 [7530337] EMBO J. 1995 May 1;14(9):1961-9 [7744003] Cell. 1995 Aug 11;82(3):405-14 [7634330] Biochem Cell Biol. 1994 Nov-Dec;72(11-12):471-4 [7544586] Immunol Today. 1995 Jun;16(6):294-7 [7662099] Science. 1996 Jan 26;271(5248):521-5 [8560270] Curr Opin Cell Biol. 1996 Apr;8(2):159-67 [8791422] Crit Rev Immunol. 1997;17(2):155-78 [9094451] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage. AN - 69758754; 10329616 AB - The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax. C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax+/- genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax+/- or bax-/- mice compared with bax+/+ mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma. JF - The EMBO journal AU - Shibata, M A AU - Liu, M L AU - Knudson, M C AU - Shibata, E AU - Yoshidome, K AU - Bandey, T AU - Korsmeyer, S J AU - Green, J E AD - Laboratory of Cell Regulation and Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/05/17/ PY - 1999 DA - 1999 May 17 SP - 2692 EP - 2701 VL - 18 IS - 10 SN - 0261-4189, 0261-4189 KW - Antigens, Polyomavirus Transforming KW - 0 KW - Bax protein, mouse KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - RNA, Messenger KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Index Medicus KW - Animals KW - Hyperplasia -- pathology KW - Mice KW - Mice, Transgenic KW - RNA, Messenger -- genetics KW - Gene Expression Regulation, Neoplastic KW - Genotype KW - Tumor Suppressor Protein p53 -- genetics KW - Gene Dosage KW - Proto-Oncogene Proteins c-bcl-2 -- genetics KW - Immunohistochemistry KW - Mutation KW - Cell Division KW - Breast Neoplasms -- genetics KW - Precancerous Conditions -- genetics KW - Apoptosis -- genetics KW - Breast Neoplasms -- pathology KW - Proto-Oncogene Proteins -- genetics KW - Ploidies KW - Antigens, Polyomavirus Transforming -- genetics KW - Breast Neoplasms -- ultrastructure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69758754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Haploid+loss+of+bax+leads+to+accelerated+mammary+tumor+development+in+C3%281%29%2FSV40-TAg+transgenic+mice%3A+reduction+in+protective+apoptotic+response+at+the+preneoplastic+stage.&rft.au=Shibata%2C+M+A%3BLiu%2C+M+L%3BKnudson%2C+M+C%3BShibata%2C+E%3BYoshidome%2C+K%3BBandey%2C+T%3BKorsmeyer%2C+S+J%3BGreen%2C+J+E&rft.aulast=Shibata&rft.aufirst=M&rft.date=1999-05-17&rft.volume=18&rft.issue=10&rft.spage=2692&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1991 Jul 25;352(6333):345-7 [1852210] Nature. 1990 Nov 22;348(6299):334-6 [2250705] Cell. 1993 Aug 27;74(4):597-608 [8358789] Cell. 1993 Aug 27;74(4):609-19 [8358790] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Nature. 1994 May 26;369(6478):321-3 [8183370] Oncogene. 1994 Jun;9(6):1799-805 [8183579] Cancer Res. 1994 Sep 15;54(18):4855-78 [8069852] Cancer Res. 1994 Nov 1;54(21):5501-7 [7923184] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11236-40 [7972041] Cell. 1995 Jan 27;80(2):285-91 [7834748] Cell. 1995 Jan 27;80(2):293-9 [7834749] Nature. 1995 Apr 20;374(6524):733-6 [7715730] Nature. 1995 Apr 20;374(6524):736-9 [7715731] Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7834-8 [7644501] Cancer Res. 1995 Oct 1;55(19):4471-8 [7671262] Science. 1995 Oct 6;270(5233):96-9 [7569956] Genes Dev. 1996 Jan 1;10(1):1-15 [8557188] Genes Dev. 1996 Feb 15;10(4):461-77 [8600029] Am J Pathol. 1996 May;148(5):1567-76 [8623925] Cancer Res. 1996 Jul 1;56(13):2998-3003 [8674054] Nature. 1997 Feb 13;385(6617):637-40 [9024662] Mol Carcinog. 1997 Oct;20(2):168-74 [9364206] Nat Med. 1998 Jun;4(6):685-90 [9623977] Nat Med. 1998 Jul;4(7):802-7 [9662371] EMBO J. 1998 Jul 15;17(14):3878-85 [9670005] Oncogene. 1998 Dec 10;17(23):2993-3005 [9881701] N Engl J Med. 1992 Aug 6;327(6):390-8 [1320737] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of superior vermal Purkinje cell placement in mental illness. AN - 69786223; 10349043 AB - A number of neuroimaging and neuropathological studies have reported abnormalities in the cerebellar vermis in schizophrenia and bipolar disorder. In an effort to further understand vermal abnormalities in mental illness, we have analyzed ectopic placement of Purkinje-like cells. The superior cerebellar vermis was evaluated in 39 cases of severe mental illness [schizophrenia (n = 12), bipolar disease (n = 12), and depression (n = 15)]. We also examined 9 subjects with polysubstance abuse and 15 normal controls. All normally placed Purkinje cells and displaced Purkinje-like cells (i.e., in the internal granule layer and intrafoliar white matter) were counted in the same foliar field. The ratio of displaced Purkinje-like cells to total Purkinje cells and Purkinje cell density were calculated. No significant difference in the ratio of displaced to normally placed Purkinje cells or in Purkinje cell density between groups of subjects was found. Our study does not support a hypothesis of abnormalities of Purkinje cell migration or other events related to their displacement as a basis for the vermal abnormalities reported previously in schizophrenia and bipolar disorder. JF - Biological psychiatry AU - Helmkamp, C E AU - Bigelow, L B AU - Paltán-Ortiz, J D AU - Torrey, E F AU - Kleinman, J E AU - Herman, M M AD - Clinical Brain Disorders Branch, NIMH Neuroscience Center at St. Elizabeths, Washington, DC, USA. Y1 - 1999/05/15/ PY - 1999 DA - 1999 May 15 SP - 1370 EP - 1375 VL - 45 IS - 10 SN - 0006-3223, 0006-3223 KW - Index Medicus KW - Analysis of Variance KW - Cell Count KW - Alcoholism -- pathology KW - Substance-Related Disorders -- pathology KW - Humans KW - Adult KW - Depressive Disorder -- pathology KW - Bipolar Disorder -- pathology KW - Schizophrenia -- pathology KW - Male KW - Female KW - Cerebellum -- cytology KW - Purkinje Cells -- pathology KW - Cerebellum -- pathology KW - Purkinje Cells -- cytology KW - Mental Disorders -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69786223?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Evaluation+of+superior+vermal+Purkinje+cell+placement+in+mental+illness.&rft.au=Helmkamp%2C+C+E%3BBigelow%2C+L+B%3BPalt%C3%A1n-Ortiz%2C+J+D%3BTorrey%2C+E+F%3BKleinman%2C+J+E%3BHerman%2C+M+M&rft.aulast=Helmkamp&rft.aufirst=C&rft.date=1999-05-15&rft.volume=45&rft.issue=10&rft.spage=1370&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-02 N1 - Date created - 1999-07-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microsatellite instability is infrequent in azoxymethane-induced rat intestinal tumors: An assessment by capillary electrophoresis. AN - 69759549; 10329502 AB - A rat model of colon cancer in which tumors are induced by azoxymethane (AOM) is frequently used to study putative environmental agents that may modify the risk of human colon cancer development. In order to evaluate the usefulness of this model for human risk assessment, a comparison of the molecular changes associated with tumorigenesis in the rat model with those in human colon cancer is desirable. Microsatellite instability (MSI), an alteration in length of short repetitive DNA sequences associated with defective DNA mismatch repair, is an important molecular characteristic of many human colon tumors. Intestinal tumors were induced in male Fischer 344 rats injected with 15 mg/kg body wt AOM in four weekly doses. Thirteen intestinal tumors were examined for MSI at 10 different microsatellite loci, using a capillary electrophoresis (CE) method for accurate assessment of DNA length. This method was shown to have a resolution of 1 bp for a 140-bp PCR product and to be capable of detecting one mutant sequence within a background of 10 wild-type sequences. The CE method also readily distinguished a known MSI-positive human tumor sample from its matching control sample. Among the 13 rat intestinal tumors examined, only one had MSI, which was present at only a single locus. We conclude that, unlike sporadic human colon tumors in which 15-30% of tumors have MSI (usually at multiple loci), MSI is very rare in AOM-induced rat intestinal tumors. JF - Toxicology and applied pharmacology AU - Walchle, C AU - Diwan, B A AU - Shiao, Y H AU - Calvert, R J AD - Division of Basic Sciences, National Cancer Institute, Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Maryland 21702, USA. Y1 - 1999/05/15/ PY - 1999 DA - 1999 May 15 SP - 9 EP - 15 VL - 157 IS - 1 SN - 0041-008X, 0041-008X KW - Carcinogens KW - 0 KW - Azoxymethane KW - MO0N1J0SEN KW - Index Medicus KW - Rats KW - Polymerase Chain Reaction KW - Animals KW - Rats, Inbred F344 KW - Genes, p53 KW - Male KW - Electrophoresis, Capillary KW - Microsatellite Repeats KW - Colonic Neoplasms -- genetics KW - Azoxymethane -- toxicity KW - Carcinogens -- toxicity KW - Colonic Neoplasms -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69759549?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Microsatellite+instability+is+infrequent+in+azoxymethane-induced+rat+intestinal+tumors%3A+An+assessment+by+capillary+electrophoresis.&rft.au=Walchle%2C+C%3BDiwan%2C+B+A%3BShiao%2C+Y+H%3BCalvert%2C+R+J&rft.aulast=Walchle&rft.aufirst=C&rft.date=1999-05-15&rft.volume=157&rft.issue=1&rft.spage=9&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-17 N1 - Date created - 1999-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Abrogation of the hematological and biological activities of the interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein PIXY321 by neutralizing anti-PIXY321 antibodies in cancer patients receiving high-dose carboplatin. AN - 69747264; 10233876 AB - This dose-escalation study was performed to evaluate the hematologic activity, biological effects, immunogenicity, and toxicity of PIXY321 (an interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein) administered after high-dose carboplatin (CBDCA) treatment. Patients with advanced cancers received CBDCA at 800 mg/m2 intravenously on day 0 of repeated 28-day cycles. In part A of the study, patients were treated with CBDCA alone during cycle 1 and then received PIXY321 on days 1 through 18 of cycle 2 and later cycles. In part B, patients received 18 days of PIXY321 beginning on day 1 of all CBDCA cycles, including cycle 1. PIXY321 was administered subcutaneously in 2 divided doses. Total doses of 135, 250, 500, 750, and 1,000 micrograms/m2/d were administered to successive cohorts of 3 to 6 patients in part A. In part B, patient groups received PIXY321 doses of 750, 1,000, and 1,250 micrograms/m2/d. The hematologic effects of PIXY321 were assessed in the first 2 cycles of therapy. Anti-PIXY321 antibody formation was assessed by enzyme-linked immunosorbent assay (ELISA) and neutralization assay. Of the 49 patients enrolled, 31 were fully evaluable for hematologic efficacy. When comparing the first B cycle (cycle B-1; with PIXY321) with the first A cycle (cycle A-1; without PIXY321), the fusion protein had no significant effect on platelet nadirs or duration of platelets less than 20,000/microL but was able to speed the time of recovery of platelet counts to 100,000/microL (15 v 20 days; P =.01). Significant improvements in neutrophil nadir and duration of ANC less than 500 were observed in cycles A-2 and B-1 (with PIXY321) as compared with cycle A-1 (without PIXY321). Initial PIXY321 prophylaxis (cycle A-2 and cycle B-1), enhanced the recovery of ANC to greater than 1,500/microL by an average of at least 8 days as compared with cycle A-1 (without PIXY321; P 10% in the DES-treated and control mice at 5-8 days of age, respectively. The data show that cell cycle kinetics, in addition to changes in morphology, are altered in the developing mouse uterus following neonatal exposure to DES. JF - Toxicologic Pathology AU - Yoshida, Akiyoshi AU - Newbold, Retha R AU - Dixon, Darlene AD - Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, dixon@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 325 EP - 333 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 27 IS - 3 SN - 0192-6233, 0192-6233 KW - Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755139294?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Effects+of+Neonatal+Diethylstilbestrol+%28DES%29+Exposure+on+Morphology+and+Growth+Patterns+of+Endometrial+Epithelial+Cells+in+CD-1+Mice&rft.au=Yoshida%2C+Akiyoshi%3BNewbold%2C+Retha+R%3BDixon%2C+Darlene&rft.aulast=Yoshida&rft.aufirst=Akiyoshi&rft.date=1999-05-01&rft.volume=27&rft.issue=3&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339902700308 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339902700308 ER - TY - JOUR T1 - Disseminated Thrombosis and Bone Infarction in Female Rats Following Inhalation Exposure to 2-Butoxyethanol AN - 755139269; 13645970 AB - Groups of 10 male and 10 female F344/N rats were exposed to 0, 31, 62.5, 125, 250, and 500 ppm of 2-butoxyethanol (BE) by inhalation, 6 hr/day, 5 days/wk, for 13 wk. Four moribund female rats from the 500 ppm group were sacrificed during the first 4 days of exposure, and 1 moribund female from the same group was sacrificed during week 5. Dark irregular mottling and/or loss of the distal tail were noted in sacrificed moribund rats. Similar gross lesions were noted in the terminally sacrificed females exposed to 500 ppm BE. Histologic changes noted in the day 4 sacrificed moribund rats included disseminated thrombosis involving the coccygeal vertebrae, cardiac atrium, lungs, liver, pulp of the incisor teeth, and the submucosa of the anterior section of the nasal cavity. Alterations noted in coccygeal vertebrae from the 500 ppm sacrificed moribund rats included ischemic necrosis and/or degeneration of bone marrow cells, bone-lining cells, osteocytes (within cortical and trabecular bone), and chondrocytes (both articular and growth plate), changes that are consistent with an infarction process. The moribund female rat that was sacrificed during week 5 and those female rats treated with 500 ppm and sacrificed following 13 wk of treatment lacked thrombi, but they had coccygeal vertebral changes consistent with prior infarction and transient or complete bone growth arrest. No bone lesions or thrombi were noted in the male rats treated with the same doses of BE. In conclusion, exposure to 500 ppm BE vapors caused acute disseminated thrombosis and bone infarction in female rats. Possible pathogenic mechanisms are discussed. JF - Toxicologic Pathology AU - Nyska, Abraham AU - Maronpot, Robert R AU - Long, Philip H AU - Roycroft, Joseph H AU - Hailey, James R AU - Travlos, Gregory S AU - Ghanayem, Burhan I AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, nyska[AT] niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 287 EP - 294 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 27 IS - 3 SN - 0192-6233, 0192-6233 KW - Calcium & Calcified Tissue Abstracts; Toxicology Abstracts UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/755139269?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+Pathology&rft.atitle=Disseminated+Thrombosis+and+Bone+Infarction+in+Female+Rats+Following+Inhalation+Exposure+to+2-Butoxyethanol&rft.au=Nyska%2C+Abraham%3BMaronpot%2C+Robert+R%3BLong%2C+Philip+H%3BRoycroft%2C+Joseph+H%3BHailey%2C+James+R%3BTravlos%2C+Gregory+S%3BGhanayem%2C+Burhan+I&rft.aulast=Nyska&rft.aufirst=Abraham&rft.date=1999-05-01&rft.volume=27&rft.issue=3&rft.spage=287&rft.isbn=&rft.btitle=&rft.title=Toxicologic+Pathology&rft.issn=01926233&rft_id=info:doi/10.1177%2F019262339902700304 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-09-01 N1 - Last updated - 2011-12-14 DO - http://dx.doi.org/10.1177/019262339902700304 ER - TY - JOUR T1 - Neutrophils in galactose-fed dogs: suppressed apoptosis and increased adhesion to retinal capillary endothelial cells. AN - 70783497; 10509875 AB - Dogs fed a diet containing 30% galactose develop diabetes-like retinal capillary changes. As retinal capillary occlusion is commonly observed in diabetic retinopathy, neutrophil apoptosis and the interaction of neutrophils with retinal capillary endothelial cells were investigated. Neutrophils were isolated with Ficoll-Hypaque centrifugation from dogs fed a 30% galactose diet and dogs fed a normal, control diet containing 30% non-nutrient filler. Apoptosis of neutrophils was microscopically examined after incubation at 37 degrees C for 3 hours with either 100 U/mL tumor necrosis factor alpha (TNF-alpha), 2 microg/mL cycloheximide or 50 ng/mL phorbol 12-myristate 13-acetate (PMA). Neutrophil adhesion to dog retinal capillary endothelial cells was examined by counting the cells attached to the surface of endothelial cells after the incubation in the presence of either 100 U/mL TNF-alpha or 5 microg/mL lipopolysaccharides (LPS) at 37 degrees C for 3 hours. With all three stimulants TNF-alpha, cycloheximide and PMA, the rate of apoptosis was significantly lower for neutrophils isolated from galactose-fed dogs compared to control dogs fed a normal diet. Preincubation of neutrophils from control dogs in medium containing 30% galactose for 3 hours did not affect the rate of apoptosis. Neutrophil adhesion to retinal capillary endothelial cells induced by incubation in the presence of either 100 U/mL TNF-alpha or 5 microg/ml LPS was significantly higher with neutrophils isolated from galactose-fed dogs than those from control dogs. The data indicate that long-term galactose feeding is essential with development of various neutrophil dysfunctions. These neutrophil changes may contribute to the development of retinal microangiopathy associated with diabetes and galactosemia. JF - Journal of diabetes and its complications AU - Ohta, N AU - Tsai, J Y AU - Secchi, E F AU - Kador, P F AU - Sato, S AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1850, USA. PY - 1999 SP - 151 EP - 158 VL - 13 IS - 3 SN - 1056-8727, 1056-8727 KW - Protein Synthesis Inhibitors KW - 0 KW - Tumor Necrosis Factor-alpha KW - Cycloheximide KW - 98600C0908 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Protein Kinase C -- metabolism KW - Animals KW - Protein Synthesis Inhibitors -- pharmacology KW - Capillaries -- pathology KW - Cycloheximide -- pharmacology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Enzyme Activation -- drug effects KW - Dogs KW - Tetradecanoylphorbol Acetate -- pharmacology KW - DNA Fragmentation KW - Male KW - Neutrophils -- pathology KW - Apoptosis KW - Diabetes Mellitus, Experimental -- pathology KW - Endothelium, Vascular -- pathology KW - Diabetes Mellitus, Experimental -- chemically induced KW - Retinal Vessels -- pathology KW - Cell Adhesion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70783497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+diabetes+and+its+complications&rft.atitle=Neutrophils+in+galactose-fed+dogs%3A+suppressed+apoptosis+and+increased+adhesion+to+retinal+capillary+endothelial+cells.&rft.au=Ohta%2C+N%3BTsai%2C+J+Y%3BSecchi%2C+E+F%3BKador%2C+P+F%3BSato%2C+S&rft.aulast=Ohta&rft.aufirst=N&rft.date=1999-05-01&rft.volume=13&rft.issue=3&rft.spage=151&rft.isbn=&rft.btitle=&rft.title=Journal+of+diabetes+and+its+complications&rft.issn=10568727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-11-01 N1 - Date created - 1999-11-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antisense oligonucleotide inhibition of serine/threonine kinases: an innovative approach to cancer treatment. AN - 69982739; 10454218 AB - The identification of genes that confer a growth advantage on neoplastic cells and the understanding of the genetic mechanism(s) responsible for their activation have made possible a direct genetic approach to cancer treatment using nucleic acid therapeutics. Moreover, the ability to block the expression of individual genes that promote carcinogenesis provides a powerful tool to explore the molecular basis of normal growth regulation, as well as the opportunity for therapeutic intervention. One technique for turning off a single activated gene is the use of antisense oligodeoxynucleotides and their analogs for inhibition of gene expression. The serine/threonine kinases are involved in mediating intracellular responses to external signals, such as growth factors, hormones, and neurotransmitters, and are involved in cell proliferation and oncogenesis. Described herein are recent studies supporting the potential use of oligonucleotides targeting these kinases as chemotherapeutic agents for cancer treatment. The serine/threonine kinases included here are protein kinase A, protein kinase C, and c-raf-1 kinase. JF - Pharmacology & therapeutics AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA. PY - 1999 SP - 437 EP - 449 VL - 82 IS - 2-3 SN - 0163-7258, 0163-7258 KW - Antineoplastic Agents KW - 0 KW - Oligonucleotides, Antisense KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Index Medicus KW - Protein Kinase C -- antagonists & inhibitors KW - Tumor Cells, Cultured KW - Humans KW - Cell Division -- drug effects KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Protein-Serine-Threonine Kinases -- pharmacology KW - Neoplasms -- drug therapy KW - Protein-Serine-Threonine Kinases -- drug effects KW - Oligonucleotides, Antisense -- pharmacology KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69982739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+therapeutics&rft.atitle=Antisense+oligonucleotide+inhibition+of+serine%2Fthreonine+kinases%3A+an+innovative+approach+to+cancer+treatment.&rft.au=Cho-Chung%2C+Y+S&rft.aulast=Cho-Chung&rft.aufirst=Y&rft.date=1999-05-01&rft.volume=82&rft.issue=2-3&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-26 N1 - Date created - 1999-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cyclin-dependent kinases: initial approaches to exploit a novel therapeutic target. AN - 69979012; 10454206 AB - Cyclin-dependent kinases (CDKs) have been recognized as key regulators of cell cycle progression. Alteration and deregulation of CDK activity are pathogenic hallmarks of neoplasia. Therefore, inhibitors or modulators would be of interest to explore as novel therapeutic agents in cancer, as well as other hyperproliferative disorders. Flavopiridol is a semisynthetic flavonoid that emerged from an empirical screening program as a potent antiproliferative agent that mechanistic studies demonstrated to directly inhibit CDKs 1, 2, and 4 as a competitive ATP site antagonist. Initial clinical trials have shown that concentrations that inhibit cell proliferation and CDK activity in vitro can be safely achieved in humans, and additional clinical trials will establish its clinical potential. To address the need for additional chemotypes that may serve as lead structures for drugs that would not have the toxicities associated with flavopiridol, compounds with a similar pattern of cell growth inhibitory activity in the National Cancer Institute's in vitro anticancer drug screen have been recognized by the computer-assisted pattern recognition algorithm COMPARE and then screened for anti-CDK activity in a biochemical screen. The benzodiazepine derivative NSC 664704 (7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one) was revealed by that approach as a moderately potent (IC50 0.4 microM) inhibitor of CDK2, which in initial experiments shows evidence of causing cell cycle redistribution in living cells. NSC 664704 is, therefore, a candidate for further structural optimization, guided in part by understanding of the ATP-binding site in CDK2. This approach represents one way of combining empirical screening information with structure-based design to derive novel candidate therapeutic agents directed against an important cellular target. JF - Pharmacology & therapeutics AU - Sausville, E A AU - Zaharevitz, D AU - Gussio, R AU - Meijer, L AU - Louarn-Leost, M AU - Kunick, C AU - Schultz, R AU - Lahusen, T AU - Headlee, D AU - Stinson, S AU - Arbuck, S G AU - Senderowicz, A AD - Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD 20852, USA. PY - 1999 SP - 285 EP - 292 VL - 82 IS - 2-3 SN - 0163-7258, 0163-7258 KW - Antineoplastic Agents KW - 0 KW - Enzyme Inhibitors KW - Cyclin-Dependent Kinases KW - EC 2.7.11.22 KW - Index Medicus KW - Animals KW - Humans KW - In Vitro Techniques KW - Clinical Trials as Topic KW - Neoplasms -- drug therapy KW - Cyclin-Dependent Kinases -- therapeutic use KW - Enzyme Inhibitors -- therapeutic use KW - Cyclin-Dependent Kinases -- antagonists & inhibitors KW - Antineoplastic Agents -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69979012?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacology+%26+therapeutics&rft.atitle=Cyclin-dependent+kinases%3A+initial+approaches+to+exploit+a+novel+therapeutic+target.&rft.au=Sausville%2C+E+A%3BZaharevitz%2C+D%3BGussio%2C+R%3BMeijer%2C+L%3BLouarn-Leost%2C+M%3BKunick%2C+C%3BSchultz%2C+R%3BLahusen%2C+T%3BHeadlee%2C+D%3BStinson%2C+S%3BArbuck%2C+S+G%3BSenderowicz%2C+A&rft.aulast=Sausville&rft.aufirst=E&rft.date=1999-05-01&rft.volume=82&rft.issue=2-3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Pharmacology+%26+therapeutics&rft.issn=01637258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-26 N1 - Date created - 1999-10-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pancreaticoduodenectomy for chronic pancreatitis: a case report and literature review. AN - 69931255; 10430385 AB - This is a case report of a patient with chronic pancreatitis who presented with biliary, duodenal and portal vein obstruction, a mass in the head of the pancreas, and a CA 19-9 level of 372 U/ml. Thus, the concern was raised as to the possibility of pancreatic cancer in this patient. We discuss the difficulties in the diagnosis of pancreatic cancer in patients with chronic pancreatitis and the treatment options available for patients with chronic pancreatitis where the significant findings involve the head of the pancreas. Finally, a brief review is given describing the pertinent literature on the surgical treatment of chronic pancreatitis and the current indications of pancreaticoduodenectomy for chronic pancreatitis. JF - Hepato-gastroenterology AU - Riker, A AU - Bartlett, D AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. PY - 1999 SP - 2005 EP - 2010 VL - 46 IS - 27 SN - 0172-6390, 0172-6390 KW - CA-19-9 Antigen KW - 0 KW - Index Medicus KW - Pancreatic Neoplasms -- diagnosis KW - Pancreatic Function Tests KW - Pancreas -- pathology KW - CA-19-9 Antigen -- blood KW - Cholestasis, Extrahepatic -- diagnosis KW - Diagnosis, Differential KW - Humans KW - Cholestasis, Extrahepatic -- surgery KW - Tomography, X-Ray Computed KW - Biopsy, Needle KW - Common Bile Duct Diseases -- diagnosis KW - Cholangiopancreatography, Endoscopic Retrograde KW - Common Bile Duct Diseases -- surgery KW - Stents KW - Chronic Disease KW - Middle Aged KW - Male KW - Pancreatic Neoplasms -- surgery KW - Pancreaticoduodenectomy KW - Pancreatitis, Alcoholic -- surgery KW - Pancreatitis, Alcoholic -- diagnosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69931255?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepato-gastroenterology&rft.atitle=Pancreaticoduodenectomy+for+chronic+pancreatitis%3A+a+case+report+and+literature+review.&rft.au=Riker%2C+A%3BBartlett%2C+D&rft.aulast=Riker&rft.aufirst=A&rft.date=1999-05-01&rft.volume=46&rft.issue=27&rft.spage=2005&rft.isbn=&rft.btitle=&rft.title=Hepato-gastroenterology&rft.issn=01726390&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-22 N1 - Date created - 1999-09-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Central nervous system serotonin and personality as variables contributing to excessive alcohol consumption in non-human primates. AN - 69899998; 10414617 AB - Non-human primates will readily consume an alcohol solution for its reinforcing effects when such a solution is palatable, with some subjects consuming alcohol to excess. In this review, we discuss variables that contribute to high alcohol consumption and the behaviours that are correlated with it in a non-human primate model. Developmental and behavioural correlates of central nervous system (CNS) serotonergic activity, as measured by concentrations of the serotonin metabolite 5-hydroxyindol-3-ylacetic acid (5-HIAA) in the cerebrospinal fluid (CSF), were used to investigate neurogenetic influences on alcohol consumption, as well as personality traits that characterize excessive alcohol intake. Inter-individual differences in CSF 5-HIAA concentrations were shown to have trait-like qualities, and with stable inter-individual differences across time and settings. Research has shown numerous similarities between human and non-human primates with respect to Type I- and II-like alcohol abuse and their associated behaviours. In the present series of studies, features characteristic of Type I alcohol misuse, such as high levels of anxiety, hypothalamic-pituitary-adrenal output, and situational stress predicted high alcohol intake. Primates with low CSF 5-HIAA concentrations also exhibited behaviours characteristic of Type II alcohol abuse. Principal among the traits that these subjects exhibited were deficits in impulse control. For example, subjects with low CSF 5-HIAA concentrations engaged in spontaneous behaviours that bring reinforcement but placed them at risk, such as entering food baited traps, jumping from dangerous heights to get from one tree to another, and consuming large amounts of alcohol. They can be characterized by other Type II-like deficits, such as impaired social competence, social alienation, and unrestrained, violent aggression. Non-human primates with low CSF 5-HIAA concentrations also exhibited high intrinsic tolerance following modest intakes of alcohol, and high rates of aggression during intoxication. High preferences for sweet solutions were shown to predict excessive alcohol consumption. Maternal and paternal genetic influences played major roles in producing low CNS serotonin function and excessive alcohol consumption. These genetic influences on serotonin function were exacerbated by early rearing experiences, particularly parental deprivation. JF - Alcohol and alcoholism (Oxford, Oxfordshire) AU - Higley, J D AU - Bennett, A J AD - Laboratory of Clinical Studies, DICBR, NIAAA, Poolesville, MD 20837-0529, USA. PY - 1999 SP - 402 EP - 418 VL - 34 IS - 3 SN - 0735-0414, 0735-0414 KW - Serotonin KW - 333DO1RDJY KW - Index Medicus KW - Severity of Illness Index KW - Rats KW - Animals KW - Humans KW - Central Nervous System -- metabolism KW - Personality Disorders -- diagnosis KW - Serotonin -- cerebrospinal fluid KW - Personality Disorders -- etiology KW - Alcoholism -- diagnosis KW - Alcoholism -- cerebrospinal fluid KW - Personality Disorders -- psychology KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69899998?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcohol+and+alcoholism+%28Oxford%2C+Oxfordshire%29&rft.atitle=Central+nervous+system+serotonin+and+personality+as+variables+contributing+to+excessive+alcohol+consumption+in+non-human+primates.&rft.au=Higley%2C+J+D%3BBennett%2C+A+J&rft.aulast=Higley&rft.aufirst=J&rft.date=1999-05-01&rft.volume=34&rft.issue=3&rft.spage=402&rft.isbn=&rft.btitle=&rft.title=Alcohol+and+alcoholism+%28Oxford%2C+Oxfordshire%29&rft.issn=07350414&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-30 N1 - Date created - 1999-09-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hypericum perforatum extracts as potential antidepressants. AN - 69895518; 10411209 AB - Extracts of Hypericum perforatum have been used in the treatment of mild to moderate depression for many years in Europe. More recently, these extracts have become available in the USA as dietary supplements and have been popularly used to improve mood. In support of this practice, data from several controlled clinical studies suggest that Hypericum perforatum is better than placebo and as effective as established antidepressant drugs. These data have, however, several limitations that should temper our enthusiasm and argue for more research before accepting Hypericum perforatum extracts into our pharmacopoeia of established antidepressants. Extant data on the possible effects of Hypericum perforatum extracts in depression are here critically reviewed and plans for further research presented. JF - The Journal of pharmacy and pharmacology AU - Vitiello, B AD - National Institute of Mental Health, Bethesda, MD, USA. bvitiell@nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 513 EP - 517 VL - 51 IS - 5 SN - 0022-3573, 0022-3573 KW - Antidepressive Agents KW - 0 KW - Plant Extracts KW - Index Medicus KW - Phytotherapy KW - Humans KW - Plant Extracts -- therapeutic use KW - Clinical Trials as Topic KW - Plant Extracts -- adverse effects KW - Theales -- therapeutic use KW - Theales -- chemistry KW - Antidepressive Agents -- therapeutic use KW - Antidepressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69895518?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacy+and+pharmacology&rft.atitle=Hypericum+perforatum+extracts+as+potential+antidepressants.&rft.au=Vitiello%2C+B&rft.aulast=Vitiello&rft.aufirst=B&rft.date=1999-05-01&rft.volume=51&rft.issue=5&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacy+and+pharmacology&rft.issn=00223573&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-09 N1 - Date created - 1999-09-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Ala99ser mutation in RI alpha regulatory subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth. AN - 69875202; 10395071 AB - Expression of the RIalpha regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIalpha was replaced with Ser (RIalpha-p) for the structure-function analysis of RIalpha. MCF-7 hormone-dependent breast cancer cells were transfected with an expression vector for the wild-type RIalpha or mutant RIalpha-p. Overexpression of RIalpha-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RIalpha overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIbeta, suppressed RIalpha and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I. JF - Molecular and cellular biochemistry AU - Lee, G R AU - Kim, S N AU - Noguchi, K AU - Park, S D AU - Hong, S H AU - Cho-Chung, Y S AD - Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892-1750, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 77 EP - 86 VL - 195 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Cyclic AMP-Dependent Protein Kinase RIalpha Subunit KW - 0 KW - Isoenzymes KW - PRKAR1A protein, human KW - Serine KW - 452VLY9402 KW - Cyclic AMP KW - E0399OZS9N KW - Cyclic AMP-Dependent Protein Kinase Type II KW - EC 2.7.11.11 KW - Cyclic AMP-Dependent Protein Kinases KW - Alanine KW - OF5P57N2ZX KW - Index Medicus KW - Humans KW - Isoenzymes -- genetics KW - Isoenzymes -- metabolism KW - Enzyme Activation -- genetics KW - Apoptosis -- genetics KW - Tumor Cells, Cultured KW - Isoenzymes -- physiology KW - Amino Acid Substitution -- genetics KW - Transfection KW - Mutagenesis, Site-Directed -- physiology KW - Cell Division -- genetics KW - Breast Neoplasms -- genetics KW - Breast Neoplasms -- pathology KW - Cyclic AMP -- metabolism KW - Neoplasms, Hormone-Dependent -- pathology KW - Alanine -- genetics KW - Cyclic AMP-Dependent Protein Kinases -- genetics KW - Cyclic AMP -- physiology KW - Neoplasms, Hormone-Dependent -- genetics KW - Serine -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69875202?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=Ala99ser+mutation+in+RI+alpha+regulatory+subunit+of+protein+kinase+A+causes+reduced+kinase+activation+by+cAMP+and+arrest+of+hormone-dependent+breast+cancer+cell+growth.&rft.au=Lee%2C+G+R%3BKim%2C+S+N%3BNoguchi%2C+K%3BPark%2C+S+D%3BHong%2C+S+H%3BCho-Chung%2C+Y+S&rft.aulast=Lee&rft.aufirst=G&rft.date=1999-05-01&rft.volume=195&rft.issue=1-2&rft.spage=77&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=03008177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-28 N1 - Date created - 1999-10-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - CONF T1 - Drug abuse treatment entry and engagement: report of a meeting on treatment readiness. AN - 69860418; 10392794 AB - Although the effectiveness of drug abuse treatment has been demonstrated repeatedly, many drug abusers do not enter treatment, many who do enter leave prematurely, and relapse following treatment is common. To further research treatment entry and engagement, the National Institute on Drug Abuse convened scientists representing diverse research traditions in December 1996. This article summarizes meeting presentations and recommendations. Presentations focused on treatment readiness/motivation for change, ethnographic reports of drug abusers' perceptions of and attitudes toward treatment, and reports on alternative treatments for high-risk drug abusers. Recommendations focused on the potential contribution of qualitative research, integration of qualitative and quantitative research approaches, development of flexible treatment approaches that are cognizant of patients' life circumstances, and services research to improve the organization and delivery of drug abuse treatment. JF - Journal of clinical psychology AU - Battjes, R J AU - Onken, L S AU - Delany, P J Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 643 EP - 657 VL - 55 IS - 5 KW - Index Medicus KW - Life Style KW - Attitude of Health Personnel KW - Risk-Taking KW - Ethnic Groups KW - Humans KW - Program Development KW - Substance-Related Disorders -- therapy KW - Patient Compliance UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69860418?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=conference&rft.jtitle=Journal+of+clinical+psychology&rft.atitle=Drug+abuse+treatment+entry+and+engagement%3A+report+of+a+meeting+on+treatment+readiness.&rft.au=Battjes%2C+R+J%3BOnken%2C+L+S%3BDelany%2C+P+J&rft.aulast=Battjes&rft.aufirst=R&rft.date=1999-05-01&rft.volume=55&rft.issue=5&rft.spage=643&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+psychology&rft.issn=00219762&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-23 N1 - Date created - 1999-07-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interferon enhances the activity of the anticancer ribonuclease, onconase. AN - 69852040; 10386856 AB - Interferons (IFN) are biologic agents involved in the antiviral response and the inhibition of tumor growth. Biochemical pathways of IFN action include the double-stranded RNA-activated oligoadenylate synthetase, RNase L, and double-stranded RNA-dependent protein kinase (PKR). Extracellular ribonucleases, especially onconase, also display antiviral and antitumor properties and involve degradation of RNA. We find that IFN increases the anticancer activity of onconase. These two agents work synergistically, and the effect is seen at the level of translation probably because of the degradation of tRNA. JF - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research AU - Vasandani, V M AU - Castelli, J C AU - Hott, J S AU - Saxena, S AU - Mikulski, S M AU - Youle, R J AD - Biochemistry Section, Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892-1414, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 447 EP - 454 VL - 19 IS - 5 SN - 1079-9907, 1079-9907 KW - Antineoplastic Agents KW - 0 KW - Egg Proteins KW - Interferons KW - 9008-11-1 KW - Ribonucleases KW - EC 3.1.- KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Rana pipiens KW - Protein Biosynthesis -- drug effects KW - Animals KW - Tumor Cells, Cultured KW - Logistic Models KW - Fibrosarcoma -- drug therapy KW - Fibrosarcoma -- enzymology KW - Drug Synergism KW - Ribonucleases -- pharmacology KW - Interferons -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Egg Proteins -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69852040?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.atitle=Interferon+enhances+the+activity+of+the+anticancer+ribonuclease%2C+onconase.&rft.au=Vasandani%2C+V+M%3BCastelli%2C+J+C%3BHott%2C+J+S%3BSaxena%2C+S%3BMikulski%2C+S+M%3BYoule%2C+R+J&rft.aulast=Vasandani&rft.aufirst=V&rft.date=1999-05-01&rft.volume=19&rft.issue=5&rft.spage=447&rft.isbn=&rft.btitle=&rft.title=Journal+of+interferon+%26+cytokine+research+%3A+the+official+journal+of+the+International+Society+for+Interferon+and+Cytokine+Research&rft.issn=10799907&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-11 N1 - Date created - 1999-08-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Uteroglobin: a novel cytokine? AN - 69841173; 10379362 AB - Blastokinin or uteroglobin (UG) is a steroid-inducible, evolutionarily conserved, multifunctional protein secreted by the mucosal epithelial of virtually all mammals. It is present in the blood and in other body fluids including urine. An antigen immunoreactive to UG antibody is also detectable in the mucosal epithelia of all vertebrates. UG-binding proteins (putative receptor), expressed on several normal and cancer cell types, have been characterized. The human UG gene is mapped to chromosome 11q12.2 13.1, a region that is frequently rearranged or deleted in many cancers. The generation of UG knockout mice revealed that disruption of this gene causes: (i) severe renal disease due to an abnormal deposition of fibronectin and collagen in the glomeruli; (ii) predisposition to a high incidence of malignancies; and (iii) a lack of polychlorinated biphenyl binding and increased oxygen toxicity in the lungs. The mechanism(s) of UG action is likely to be even more complex as it also functions via a putative receptor-mediated pathway that has not yet been clearly defined. Molecular characterization of the UG receptor and signal transduction via this receptor pathway may show that this protein belongs to a novel cytokine/chemokine family. JF - Cellular and molecular life sciences : CMLS AU - Mukherjee, A B AU - Kundu, G C AU - Mantile-Selvaggi, G AU - Yuan, C J AU - Mandal, A K AU - Chattopadhyay, S AU - Zheng, F AU - Pattabiraman, N AU - Zhang, Z AD - Section on Developmental Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1830, USA. mukherja@exchange.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 771 EP - 787 VL - 55 IS - 5 SN - 1420-682X, 1420-682X KW - Cytokines KW - 0 KW - DNA, Complementary KW - Receptors, Cytokine KW - Uteroglobin KW - 9060-09-7 KW - Index Medicus KW - Receptors, Cytokine -- physiology KW - Animals KW - DNA, Complementary -- genetics KW - Genes, Tumor Suppressor KW - Models, Molecular KW - Humans KW - Amino Acid Sequence KW - Mice KW - Mice, Transgenic KW - Cloning, Molecular KW - Mice, Knockout KW - Base Sequence KW - Molecular Sequence Data KW - Gene Expression Regulation KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Cytokines -- genetics KW - Uteroglobin -- genetics KW - Cytokines -- physiology KW - Cytokines -- chemistry KW - Uteroglobin -- chemistry KW - Uteroglobin -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69841173?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=Uteroglobin%3A+a+novel+cytokine%3F&rft.au=Mukherjee%2C+A+B%3BKundu%2C+G+C%3BMantile-Selvaggi%2C+G%3BYuan%2C+C+J%3BMandal%2C+A+K%3BChattopadhyay%2C+S%3BZheng%2C+F%3BPattabiraman%2C+N%3BZhang%2C+Z&rft.aulast=Mukherjee&rft.aufirst=A&rft.date=1999-05-01&rft.volume=55&rft.issue=5&rft.spage=771&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suicidal ideation among the United States drinking population: results from the National Longitudinal Alcohol Epidemiologic Survey. AN - 69825617; 10371272 AB - Data from a national representative sample of adults was used to identify major risk factors of suicidal ideation among the U.S. drinking population. Data from a sample of 18,352 current drinkers, 18 years of age and older, were analyzed by means of multiple logistic regression analysis. In these analyses, multivariate associations were examined between risk factors for suicidal ideation and the occurrence of suicidal ideation. For men and women, past year major depression and alcohol dependence were identified as risk factors of suicidal ideation, with major depression having the more sizable impact. Suicidal ideation was increased among men with a past alcohol use disorder, and elevated among women who had used drugs nonmedically and developed a drug use disorder during the past year. The occurrence of a recent physical illness and lifetime treatment for major depression among men and women increased the risk of suicidal ideation, while marriage was protective against ideation for both sexes. Unemployment and having a family history of alcoholism increased the risk of suicidal ideation among men, but not women. Major findings are discussed in terms of the impact of severity versus chronicity of psychopathology on suicidal ideation, gender roles and differential engagement in suicidal ideation, and the recognition and treatment of major depression as the single most important intervention in reducing suicidal behavior. JF - Journal of studies on alcohol AU - Grant, B F AU - Hasin, D S AD - Division of Biometry and Epidemiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-7003, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 422 EP - 429 VL - 60 IS - 3 SN - 0096-882X, 0096-882X KW - Index Medicus KW - Socioeconomic Factors KW - Analysis of Variance KW - Humans KW - Adult KW - Diagnosis, Dual (Psychiatry) KW - Aged KW - Middle Aged KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Depressive Disorder, Major -- psychology KW - Alcohol Drinking -- psychology KW - Depressive Disorder, Major -- epidemiology KW - Substance-Related Disorders -- psychology KW - Alcohol Drinking -- epidemiology KW - Suicide -- statistics & numerical data KW - Suicide -- psychology KW - Suicide -- prevention & control KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69825617?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol&rft.atitle=Suicidal+ideation+among+the+United+States+drinking+population%3A+results+from+the+National+Longitudinal+Alcohol+Epidemiologic+Survey.&rft.au=Grant%2C+B+F%3BHasin%2C+D+S&rft.aulast=Grant&rft.aufirst=B&rft.date=1999-05-01&rft.volume=60&rft.issue=3&rft.spage=422&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol&rft.issn=0096882X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-21 N1 - Date created - 1999-07-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhalation toxicity and carcinogenicity studies of cobalt sulfate. AN - 69823739; 10367342 AB - Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation resulted in increased incidence of alveolar/bronchiolar neoplasms and a spectrum of inflammatory, fibrotic, and proliferative lesions in the respiratory tracts of male and female rats and mice. Adrenal pheochromocytomas were increased in female rats, and possibly in male rats. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Bucher, J R AU - Hailey, J R AU - Roycroft, J R AU - Haseman, J K AU - Sills, R C AU - Grumbein, S L AU - Mellick, P W AU - Chou, B J AD - National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. bucher@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 56 EP - 67 VL - 49 IS - 1 SN - 1096-6080, 1096-6080 KW - Carcinogens KW - 0 KW - Cobalt KW - 3G0H8C9362 KW - cobalt sulfate KW - H7965X29HX KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Survival Rate KW - Sex Factors KW - Body Weight -- drug effects KW - Mice KW - Administration, Inhalation KW - Species Specificity KW - Male KW - Female KW - Cobalt -- toxicity KW - Pheochromocytoma -- chemically induced KW - Carcinogens -- toxicity KW - Lung Neoplasms -- chemically induced KW - Lung Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69823739?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Inhalation+toxicity+and+carcinogenicity+studies+of+cobalt+sulfate.&rft.au=Bucher%2C+J+R%3BHailey%2C+J+R%3BRoycroft%2C+J+R%3BHaseman%2C+J+K%3BSills%2C+R+C%3BGrumbein%2C+S+L%3BMellick%2C+P+W%3BChou%2C+B+J&rft.aulast=Bucher&rft.aufirst=J&rft.date=1999-05-01&rft.volume=49&rft.issue=1&rft.spage=56&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-03 N1 - Date created - 1999-09-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fusarium mycotoxins in corn and corn products in a high-risk area for gastric cancer in Shandong Province, China. AN - 69821894; 10367384 AB - Consumption of fermented, but not unfermented, corn pancakes has been linked with elevated stomach cancer mortality rates in rural Linqu County in Shandong Province, China. Previous surveys of fungal contamination of corn in China have detected fumonisins, which are mycotoxins produced by Fusarium moniliforme. To determine whether mycotoxins might account for the increased risk of cancer among those consuming fermented pancakes, we obtained specimens of corn, cornmeal, unfermented and fermented pancake batter, and cooked fermented pancakes from each of 16 households in Linqu County for analysis by the U.S. Department of Agriculture. Fumonisins B1, B2, and B3 were detected (> or = 0.5 microgram/g) in 19, 25, and 6% of the corn specimens, respectively, as well as in various corn products. No type A trichothecenes were detected; however, the type B trichothecenes deoxynivalenol and 15-acetyldeoxynivalenol were detected (> or = 0.5 microgram/g) in 58 and 17% of the corn specimens, respectively, and zearalenone was detected (> or = 0.5 microgram/g) in 15% of the cornmeal specimens. The mycotoxins were detected only at low levels (< 10 micrograms/g), which did not increase with fermentation. These findings do not support the hypothesis that mycotoxin contamination increases the risk of gastric cancer among those who consume fermented Chinese pancakes. JF - Journal of AOAC International AU - Groves, F D AU - Zhang, L AU - Chang, Y S AU - Ross, P F AU - Casper, H AU - Norred, W P AU - You, W C AU - Fraumeni, J F AD - National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD 20892-7244, USA. PY - 1999 SP - 657 EP - 662 VL - 82 IS - 3 SN - 1060-3271, 1060-3271 KW - Carboxylic Acids KW - 0 KW - Fumonisins KW - Mycotoxins KW - Trichothecenes KW - fumonisin B2 KW - 116355-84-1 KW - fumonisin B3 KW - 136379-59-4 KW - fumonisin B1 KW - 3ZZM97XZ32 KW - 15-acetyldeoxynivalenol KW - 88337-96-6 KW - deoxynivalenol KW - JT37HYP23V KW - Sphingosine KW - NGZ37HRE42 KW - safingol KW - OWA98U788S KW - Index Medicus KW - Animals KW - Sphingosine -- metabolism KW - Fermentation KW - Biological Assay KW - Liver -- metabolism KW - Carboxylic Acids -- analysis KW - Rats KW - Rats, Sprague-Dawley KW - Carboxylic Acids -- pharmacology KW - Food Contamination KW - Trichothecenes -- analysis KW - China KW - Male KW - Sphingosine -- analogs & derivatives KW - Zea mays -- microbiology KW - Fusarium -- metabolism KW - Stomach Neoplasms -- chemically induced KW - Zea mays -- chemistry KW - Stomach Neoplasms -- epidemiology KW - Mycotoxins -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69821894?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+AOAC+International&rft.atitle=Fusarium+mycotoxins+in+corn+and+corn+products+in+a+high-risk+area+for+gastric+cancer+in+Shandong+Province%2C+China.&rft.au=Groves%2C+F+D%3BZhang%2C+L%3BChang%2C+Y+S%3BRoss%2C+P+F%3BCasper%2C+H%3BNorred%2C+W+P%3BYou%2C+W+C%3BFraumeni%2C+J+F&rft.aulast=Groves&rft.aufirst=F&rft.date=1999-05-01&rft.volume=82&rft.issue=3&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Journal+of+AOAC+International&rft.issn=10603271&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-15 N1 - Date created - 1999-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats. AN - 69795402; 10356702 AB - A 2-yr whole-body exposure study was conducted to evaluate the chronic toxicity and possible oncogenicity of 60 Hz (power frequency) magnetic fields in rats. Groups of 100 male and 100 female F344/N rats were exposed continuously to pure, linearly polarized, transient-free 60 Hz magnetic fields at flux densities of 0 Gauss (G) (sham control), 20 milligauss (mG), 2 G, and 10 G; an additional group of 100 male and 100 female F344/N rats received intermittent (1 hr on/1 hr off) exposure to 10 G fields. Mortality patterns, body weight gains throughout the study, and the total incidence and number of malignant and benign tumors in all groups exposed to magnetic fields were similar to those found in sex-matched sham controls. Statistically significant increases in the combined incidence of C-cell adenomas and carcinomas of the thyroid were seen in male rats chronically exposed to 20 mG and 2 G magnetic fields. These increases were not seen in male rats exposed continuously or intermittently to 10 G fields or in female rats at any magnetic field exposure level. No increases in the incidence of neoplasms, which have been identified in epidemiology studies as possible targets of magnetic field action (leukemia, breast cancer, and brain cancer), were found in any group exposed to magnetic fields. There was a decrease in leukemia in male rats exposed to 10 G intermittent fields. The occurrence of C-cell tumors at the 2 lower field intensities in male rats is interpreted as equivocal evidence of carcinogenicity; data from female rats provides no evidence of carcinogenicity in that sex. These data, when considered as a whole, are interpreted as indicating that chronic exposure to pure linearly polarized 60 Hz magnetic fields has little or no effect on cancer development in the F344/N rat. JF - Toxicologic pathology AU - Boorman, G A AU - McCormick, D L AU - Findlay, J C AU - Hailey, J R AU - Gauger, J R AU - Johnson, T R AU - Kovatch, R M AU - Sills, R C AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Boorman@niehs.nih.gov PY - 1999 SP - 267 EP - 278 VL - 27 IS - 3 SN - 0192-6233, 0192-6233 KW - Index Medicus KW - Animals KW - Leukemia, Radiation-Induced -- mortality KW - Thyroid Neoplasms -- etiology KW - Evaluation Studies as Topic KW - Rats KW - Rats, Inbred F344 KW - Whole-Body Irradiation KW - Body Weight -- radiation effects KW - Adenoma -- etiology KW - Adenoma -- pathology KW - Male KW - Carcinoma, Medullary -- pathology KW - Mammary Neoplasms, Animal -- pathology KW - Sex Factors KW - Leukemia, Radiation-Induced -- pathology KW - Fibroadenoma -- etiology KW - Adenoma -- mortality KW - Leukemia, Radiation-Induced -- etiology KW - Carcinoma, Medullary -- mortality KW - Mammary Neoplasms, Animal -- etiology KW - Fibroadenoma -- pathology KW - Survival Rate KW - Fibroadenoma -- mortality KW - Carcinoma, Medullary -- etiology KW - Thyroid Neoplasms -- pathology KW - Thyroid Neoplasms -- mortality KW - Mammary Neoplasms, Animal -- mortality KW - Female KW - Radiation Injuries, Experimental -- pathology KW - Radiation Injuries, Experimental -- mortality KW - Neoplasms, Radiation-Induced -- etiology KW - Neoplasms, Radiation-Induced -- pathology KW - Electromagnetic Fields -- adverse effects KW - Neoplasms, Radiation-Induced -- mortality KW - Radiation Injuries, Experimental -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69795402?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicologic+pathology&rft.atitle=Chronic+toxicity%2Foncogenicity+evaluation+of+60+Hz+%28power+frequency%29+magnetic+fields+in+F344%2FN+rats.&rft.au=Boorman%2C+G+A%3BMcCormick%2C+D+L%3BFindlay%2C+J+C%3BHailey%2C+J+R%3BGauger%2C+J+R%3BJohnson%2C+T+R%3BKovatch%2C+R+M%3BSills%2C+R+C%3BHaseman%2C+J+K&rft.aulast=Boorman&rft.aufirst=G&rft.date=1999-05-01&rft.volume=27&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=Toxicologic+pathology&rft.issn=01926233&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Toxicol Pathol. 1999 May-Jun;27(3):286 [10356704] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lipoxygenase inhibitors as potential cancer chemopreventives. AN - 69790939; 10350444 AB - Mounting evidence suggests that lipoxygenase (LO)-catalyzed products have a profound influence on the development and progression of human cancers. Compared with normal tissues, significantly elevated levels of LO metabolites have been found in lung, prostate, breast, colon, and skin cancer cells, as well as in cells from patients with both acute and chronic leukemias. LO-mediated products elicit diverse biological activities needed for neoplastic cell growth, influencing growth factor and transcription factor activation, oncogene induction, stimulation of tumor cell adhesion, and regulation of apoptotic cell death. Agents that block LO-catalyzed activity may be effective in preventing cancer by interfering with signaling events needed for tumor growth. In fact, in a few studies, LO inhibitors have prevented carcinogen-induced lung adenomas and rat mammary gland cancers. During the past 10 years, pharmacological agents that specifically inhibit the LO-mediated signaling pathways are now commercially available to treat inflammatory diseases such as asthma, arthritis, and psoriasis. These well-characterized agents, representing two general drug effect mechanisms, are considered good candidates for clinical chemoprevention studies. One mechanism is inhibition of LO activity (5-LO and associated enzymes, or 12-LO); the second is leukotriene receptor antagonism. Although the receptor antagonists have high potential in treating asthma and other diseases where drug effects are clearly mediated by the leukotriene receptors, enzyme activity inhibitors may be better candidates for chemopreventive intervention, because inhibition of these enzymes directly reduces fatty acid metabolite production, with concomitant damping of the associated inflammatory, proliferative, and metastatic activities that contribute to carcinogenesis. However, because receptor antagonists have aerosol formulations and possible antiproliferative activity, they may also have potential, particularly in the lung, where topical application of such formulations is feasible. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Steele, V E AU - Holmes, C A AU - Hawk, E T AU - Kopelovich, L AU - Lubet, R A AU - Crowell, J A AU - Sigman, C C AU - Kelloff, G J AD - Chemoprevention Branch, Division of Cancer prevention, National Cancer Institute, Bethesda, Maryland 20892-7322, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 467 EP - 483 VL - 8 IS - 5 SN - 1055-9965, 1055-9965 KW - Anticarcinogenic Agents KW - 0 KW - Lipoxygenase Inhibitors KW - Index Medicus KW - Rats KW - Animals KW - Humans KW - Anticarcinogenic Agents -- therapeutic use KW - Lipoxygenase Inhibitors -- therapeutic use KW - Anticarcinogenic Agents -- metabolism KW - Neoplasms -- prevention & control KW - Lipoxygenase Inhibitors -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69790939?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Lipoxygenase+inhibitors+as+potential+cancer+chemopreventives.&rft.au=Steele%2C+V+E%3BHolmes%2C+C+A%3BHawk%2C+E+T%3BKopelovich%2C+L%3BLubet%2C+R+A%3BCrowell%2C+J+A%3BSigman%2C+C+C%3BKelloff%2C+G+J&rft.aulast=Steele&rft.aufirst=V&rft.date=1999-05-01&rft.volume=8&rft.issue=5&rft.spage=467&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-28 N1 - Date created - 1999-07-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - What guides early embryonic blood vessel formation? AN - 69779745; 10340752 AB - Survival of vertebrate embryos depends on their ability to assemble a correctly patterned, integrated network of blood vessels to supply oxygen and nutrients to developing tissues. The arrangement of larger caliber intraembryonic vessels, specification of arterial-venous identity, and proper placement of major branch points and arterial-venous connections are all precisely determined. A number of recent studies in both mammalian and nonmammalian vertebrate species, reviewed here, have now begun to reveal the major role played by genetically predetermined extrinsic cues in guiding the formation of early embryonic blood vessels and determining the global pattern of the vasculature. JF - Developmental dynamics : an official publication of the American Association of Anatomists AU - Weinstein, B M AD - Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2 EP - 11 VL - 215 IS - 1 SN - 1058-8388, 1058-8388 KW - Endothelial Growth Factors KW - 0 KW - Lymphokines KW - Vascular Endothelial Growth Factor A KW - Vascular Endothelial Growth Factors KW - Index Medicus KW - Animals KW - Xenopus -- embryology KW - Xenopus -- anatomy & histology KW - Mesoderm -- physiology KW - Arteries -- embryology KW - Mutagenesis KW - Zebrafish -- anatomy & histology KW - Endothelial Growth Factors -- physiology KW - Aorta -- embryology KW - Zebrafish -- embryology KW - Endoderm -- physiology KW - Lymphokines -- physiology KW - Blood Vessels -- embryology KW - Neovascularization, Physiologic -- genetics KW - Neovascularization, Physiologic -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69779745?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.atitle=What+guides+early+embryonic+blood+vessel+formation%3F&rft.au=Weinstein%2C+B+M&rft.aulast=Weinstein&rft.aufirst=B&rft.date=1999-05-01&rft.volume=215&rft.issue=1&rft.spage=2&rft.isbn=&rft.btitle=&rft.title=Developmental+dynamics+%3A+an+official+publication+of+the+American+Association+of+Anatomists&rft.issn=10588388&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-18 N1 - Date created - 1999-08-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prolactin exerts hematopoietic growth-promoting effects in vivo and partially counteracts myelosuppression by azidothymidine. AN - 69774970; 10340396 AB - Prolactin (PRL) is a neuroendocrine hormone that influences immune and hematopoietic development. The mechanism of action of this hormone in vivo remains unclear; therefore, we assessed the effects of PRL on hematopoiesis in vivo and in vitro. Normal resting mice were treated with 0, 1, 10, or 100 microg of recombinant human prolactin (rhPRL) for 4 consecutive days and euthanized on the fifth day for analysis of myeloid and erythroid progenitors in the bone marrow and spleen. Both frequencies and absolute numbers of splenic colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-e) were significantly increased in mice receiving rhPRL compared to the controls that had received saline only. Bone marrow cellularities were not significantly affected by any dose of rhPRL, but the absolute numbers and frequencies of bone marrow CFU-GM and BFU-e were augmented by rhPRL. These results suggest that rhPRL can promote hematopoiesis in vivo. Because rhPRL augments myeloid development in vivo, we examined the potential of the hormone to reverse the anemia and myelosuppression induced by azidothymidine (AZT). Mice were given rhPRL injections concurrent with 2.5 mg/mL AZT in drinking water. rhPRL partially restored hematocrits in the animals after 2 weeks of treatment and increased CFU-GM and BFU-e in both spleens and bone marrow. The experiments with AZT and rhPRL support the conclusion that the hormone increases myeloid and erythroid progenitor numbers in vivo, and they suggest that the hormone is clinically useful in reversing myelosuppression induced by AZT or other myeloablative therapies. JF - Experimental hematology AU - Woody, M A AU - Welniak, L A AU - Sun, R AU - Tian, Z G AU - Henry, M AU - Richards, S AU - Raziuddin, A AU - Longo, D L AU - Murphy, W J AD - Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 811 EP - 816 VL - 27 IS - 5 SN - 0301-472X, 0301-472X KW - Anti-HIV Agents KW - 0 KW - Recombinant Proteins KW - Zidovudine KW - 4B9XT59T7S KW - Prolactin KW - 9002-62-4 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Recombinant Proteins -- pharmacology KW - Humans KW - Hematopoietic Stem Cells -- cytology KW - Mice KW - Hematopoietic Stem Cells -- drug effects KW - Zidovudine -- adverse effects KW - Hematopoiesis -- drug effects KW - Cell Division -- drug effects KW - Anti-HIV Agents -- adverse effects KW - Zidovudine -- antagonists & inhibitors KW - Prolactin -- pharmacology KW - Anti-HIV Agents -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69774970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+hematology&rft.atitle=Prolactin+exerts+hematopoietic+growth-promoting+effects+in+vivo+and+partially+counteracts+myelosuppression+by+azidothymidine.&rft.au=Woody%2C+M+A%3BWelniak%2C+L+A%3BSun%2C+R%3BTian%2C+Z+G%3BHenry%2C+M%3BRichards%2C+S%3BRaziuddin%2C+A%3BLongo%2C+D+L%3BMurphy%2C+W+J&rft.aulast=Woody&rft.aufirst=M&rft.date=1999-05-01&rft.volume=27&rft.issue=5&rft.spage=811&rft.isbn=&rft.btitle=&rft.title=Experimental+hematology&rft.issn=0301472X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tumor angiogenesis and endothelial cell modulatory factors. AN - 69773922; 10335479 AB - Angiogenesis is the ability of preexisting vasculature to send out capillary sprouts leading to the formation of new vasculature. It is now a well-accepted idea that progression of solid tumors is intrinsically dependent on angiogenesis for growth of the primary tumor and metastatic lesions. Investigations into tumor angiogenesis have focused on inhibition of tumor neovasculature as yet another possible mechanism for impairing tumor progression. Numerous studies have characterized cellular and molecular factors important to vascular formation and development and have led to the identification and understanding of requisite interactions between endothelium, angiogenic cytokines, and the supporting matrix. These studies have also led to the identification of cytokines involved in the proteolytic disruption of the basement membrane, the migration of endothelial cells, and the proliferation and formation of neoendothelium into functional vasculature. As therapies based on antiangiogenic strategies continue to evolve and clinical trials are conducted, these agents may become an important part of the arsenal against tumor proliferation, especially given their favorable toxicity profile. This review discusses the angiogenic cytokines which have been most intensely studied and the receptors they act upon. Additionally, we discuss select proteases and their importance in the development of neovasculature. A better understanding of these components will help in the development of novel therapeutic strategies. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Desai, S B AU - Libutti, S K AD - Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 186 EP - 211 VL - 22 IS - 3 SN - 1524-9557, 1524-9557 KW - Antineoplastic Agents KW - 0 KW - Cell Adhesion Molecules KW - Cytokines KW - Endothelial Growth Factors KW - Growth Inhibitors KW - Index Medicus KW - Oncogenes KW - Humans KW - Extracellular Matrix KW - Neoplasms -- blood supply KW - Neovascularization, Pathologic -- prevention & control KW - Neoplasms -- therapy KW - Neoplasms -- genetics KW - Endothelium, Vascular UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69773922?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Tumor+angiogenesis+and+endothelial+cell+modulatory+factors.&rft.au=Desai%2C+S+B%3BLibutti%2C+S+K&rft.aulast=Desai&rft.aufirst=S&rft.date=1999-05-01&rft.volume=22&rft.issue=3&rft.spage=186&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-12 N1 - Date created - 1999-07-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: J Immunother. 1999 May;22(3):185 [10335478] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human papillomavirus vaccines for cervical cancer. AN - 69772899; 10335480 AB - Cervical cancer is one of the most common causes of cancer-related death in women. As a result of several recent advances in molecular biology, the association between human papillomavirus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Several lines of evidence suggest the importance of the host's immune response, especially cellular immune response, in the pathogenesis of HPV-associated cervical lesions. These observations form a compelling rationale for the development of vaccine therapy to combat HPV infection. Both prophylactic and therapeutic HPV vaccine strategies are being developed. Prophylactic strategies currently under investigation focus on the induction of effective humoral immune responses against subsequent HPV infection. In this respect, impressive immunoprophylactic effects have been demonstrated in animals using papillomavirus-like particles (VLPs). VLPs are antigenic and protective, but are devoid of any viral DNA that may be carcinogenic to the host. For treatment of existing HPV infection, techniques to improve cellular immunity by enhancing viral antigen recognition are being studied. For this purpose, the oncogenic proteins E6 and E7 of HPV-16 and -18 are the focus of current clinical trials for cervical cancer patients. The development of successful HPV-specific vaccines may offer an attractive alternative to existing screening and treatment programs for cervical cancer. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Murakami, M AU - Gurski, K J AU - Steller, M A AD - Section of Gynecologic Oncology, National Cancer Institute, Bethesda, Maryland, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 212 EP - 218 VL - 22 IS - 3 SN - 1524-9557, 1524-9557 KW - Papillomavirus Vaccines KW - 0 KW - Viral Vaccines KW - Index Medicus KW - Animals KW - Immunity, Cellular KW - Humans KW - Immunotherapy, Active KW - Tumor Virus Infections -- therapy KW - Tumor Virus Infections -- prevention & control KW - Female KW - Uterine Cervical Neoplasms -- prevention & control KW - Uterine Cervical Neoplasms -- therapy KW - Papillomavirus Infections -- therapy KW - Papillomavirus Infections -- prevention & control KW - Papillomaviridae -- immunology KW - Viral Vaccines -- therapeutic use KW - Uterine Cervical Neoplasms -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69772899?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=Human+papillomavirus+vaccines+for+cervical+cancer.&rft.au=Murakami%2C+M%3BGurski%2C+K+J%3BSteller%2C+M+A&rft.aulast=Murakami&rft.aufirst=M&rft.date=1999-05-01&rft.volume=22&rft.issue=3&rft.spage=212&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-12 N1 - Date created - 1999-07-12 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Taxanes as radiosensitizers for head and neck cancer. AN - 69771501; 10328592 AB - Combinations of paclitaxel and radiation therapy or paclitaxel with other chemotherapy agents and radiation have been tested with variable results in patient populations. To date, three phase I trials have been conducted using paclitaxel alone in combination with radiotherapy for the treatment of patients with head and neck cancer. Dose-limiting toxicity in the 1-hour infusion was mucositis, whereas in the 24-h/wk infusion, fever was the dose-limiting toxicity. In the long-term infusion (24 h/d, 7 d/wk), no dose-limiting toxicity was seen at the doses of paclitaxel given. In two of the protocols in which biopsies were obtained, a G2/M block was observed. A phase I protocol using paclitaxel in combination with fluorouracil and hydroxyurea with radiation and a phase II protocol using paclitaxel with cisplatin in operable head and neck cancers have been reported. Preliminary results suggest that paclitaxel in combination with radiotherapy is a reasonable experimental treatment that deserves further study in patients with stage III and IV squamous cell carcinomas of the head and neck. JF - Current opinion in oncology AU - Herscher, L L AU - Cook, J AD - National Institutes of Health, Radiation Oncology Branch, Bethesda, Maryland 20892, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 183 EP - 186 VL - 11 IS - 3 SN - 1040-8746, 1040-8746 KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Radiation-Sensitizing Agents KW - Paclitaxel KW - P88XT4IS4D KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Neoplasm Staging KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Combined Modality Therapy KW - Humans KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Clinical Trials as Topic KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use KW - Cell Cycle KW - Antineoplastic Agents, Phytogenic -- administration & dosage KW - Cisplatin -- administration & dosage KW - Paclitaxel -- administration & dosage KW - Paclitaxel -- adverse effects KW - Head and Neck Neoplasms -- radiotherapy KW - Head and Neck Neoplasms -- pathology KW - Paclitaxel -- therapeutic use KW - Radiation-Sensitizing Agents -- therapeutic use KW - Radiation-Sensitizing Agents -- adverse effects KW - Head and Neck Neoplasms -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69771501?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+opinion+in+oncology&rft.atitle=Taxanes+as+radiosensitizers+for+head+and+neck+cancer.&rft.au=Herscher%2C+L+L%3BCook%2C+J&rft.aulast=Herscher&rft.aufirst=L&rft.date=1999-05-01&rft.volume=11&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Current+opinion+in+oncology&rft.issn=10408746&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-28 N1 - Date created - 1999-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage. AN - 69769250; 10334208 AB - Epidemiological evidence suggests that certain paternal exposures to metals may increase the risk of cancer in the progeny. This effect may be associated with promutagenic damage to the sperm DNA. The latter is packed with protamines which might sequester carcinogenic metals and moderate the damage. Human protamine P2 has an amino acid motif at its N-terminus that can serve as a heavy metal trap, especially for Ni(II) and Cu(II). We have synthesized a pentadecapeptide modeling this motif, Arg-Thr-His-Gly-Gln-Ser-His-Tyr-Arg-Arg-Arg-His-Cys-Ser-Arg-amide (HP21-15) and described its complexes with Ni(II) and Cu(II), including their capacity to mediate oxidative DNA degradation [Bal et al. (1997) Chem. Res. Toxicol., 10, 906-914 and 915-921]. In the present study, effects of HP21-15 on Ni(II)- and Cu(II)-mediated DNA oxidation by H2O2 at pH 7.4 were investigated in more detail using the circular plasmid pUC19 DNA as a target, and the single/double-strand breaks and production of oxidized DNA bases, as end points. Ni(II) alone was found to promote oxidative DNA strand scission (mostly single strand breaks) and base damage, while Cu(II) alone produced the same effects, but to a much greater extent. Both metals were relatively more damaging to the pyrimidine bases than to purine bases. HP21-15 tended to increase the Ni(II)/H2O2-induced DNA breakage. In sharp contrast, the destruction of DNA strands by Cu(II)/H2O2 was almost completely prevented by HP21-15. The effect of HP21-15 on the oxidative DNA base damage varied from a limited enhancement (5-hydroxyhydantoin and thymine glycol) to slight suppression (5-hydroxycytosine, 5-hydroxyuracil, 8-oxoguanine, 8-oxoadenine, 2-hydroxyadenine, fapyguanine and fapyadenine) toward Ni(II)/H2O2. HP21-15 strongly suppressed the oxidative activity of Cu(II)/H2O2 in regard to all bases in DNA. Consistently with the above, the electron spin resonance/spin trap measurements revealed greater and more persistent generation of OH* and O2-*-like oxidants from H2O2 by the Ni(II)-HP21-15 complex than by the Cu(II)-HP21-15 complex (no O2-* was detected). Both complexes were also found to bind to DNA more strongly than HP21-15 alone. The results indicate that protamine P2 is capable of binding Ni(II) and Cu(II) and, in this way, attenuating the mediation of oxidative DNA damage by Cu(II), but not Ni(II). The effects found may be mechanistically involved in the reproductive toxicity and carcinogenicity of metals. JF - Carcinogenesis AU - Liang, R AU - Senturker, S AU - Shi, X AU - Bal, W AU - Dizdaroglu, M AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, MD 21702, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 893 EP - 898 VL - 20 IS - 5 SN - 0143-3334, 0143-3334 KW - Protamines KW - 0 KW - Purines KW - Pyrimidines KW - Reactive Oxygen Species KW - protamine P2 KW - Copper KW - 789U1901C5 KW - Nickel KW - 7OV03QG267 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Purines -- metabolism KW - Reactive Oxygen Species -- metabolism KW - Animals KW - Plasmids -- metabolism KW - DNA Damage KW - Plasmids -- genetics KW - Humans KW - Thymus Gland -- chemistry KW - Oxidation-Reduction KW - Cattle KW - Protein Binding -- drug effects KW - Oxidative Stress KW - Pyrimidines -- metabolism KW - Plasmids -- drug effects KW - Male KW - Nickel -- pharmacology KW - DNA -- metabolism KW - Protamines -- metabolism KW - Protamines -- chemistry KW - Protamines -- drug effects KW - Copper -- pharmacology KW - DNA -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69769250?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effects+of+Ni%28II%29+and+Cu%28II%29+on+DNA+interaction+with+the+N-terminal+sequence+of+human+protamine+P2%3A+enhancement+of+binding+and+mediation+of+oxidative+DNA+strand+scission+and+base+damage.&rft.au=Liang%2C+R%3BSenturker%2C+S%3BShi%2C+X%3BBal%2C+W%3BDizdaroglu%2C+M%3BKasprzak%2C+K+S&rft.aulast=Liang&rft.aufirst=R&rft.date=1999-05-01&rft.volume=20&rft.issue=5&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-28 N1 - Date created - 1999-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen. AN - 69766181; 10334193 AB - Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes. JF - Carcinogenesis AU - Xu, L AU - Flynn, B J AU - Ungar, S AU - Pass, H I AU - Linnainmaa, K AU - Mattson, K AU - Gerwin, B I AD - Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 773 EP - 783 VL - 20 IS - 5 SN - 0143-3334, 0143-3334 KW - Antigens, Polyomavirus Transforming KW - 0 KW - CDKN1A protein, human KW - Carcinogens KW - Cyclin-Dependent Kinase Inhibitor p16 KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Tumor Suppressor Protein p53 KW - Asbestos, Amosite KW - 12172-73-5 KW - Asbestos KW - 1332-21-4 KW - Index Medicus KW - Drug Resistance -- genetics KW - Humans KW - Pleural Neoplasms -- pathology KW - Aged KW - Antigens, Polyomavirus Transforming -- analysis KW - Tumor Suppressor Protein p53 -- analysis KW - Genes KW - Aged, 80 and over KW - Mesothelioma -- metabolism KW - Apoptosis -- drug effects KW - Adult KW - Mesothelioma -- pathology KW - Gene Expression Regulation -- drug effects KW - Time Factors KW - Male KW - Pleural Neoplasms -- metabolism KW - Asbestos, Amosite -- adverse effects KW - Dose-Response Relationship, Drug KW - Cell Division -- drug effects KW - Cyclin-Dependent Kinase Inhibitor p16 -- metabolism KW - Cyclins -- analysis KW - Middle Aged KW - Cyclin-Dependent Kinase Inhibitor p16 -- genetics KW - Immunohistochemistry KW - Methylation KW - Cell Line KW - Female KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Epithelial Cells -- drug effects KW - Asbestos -- adverse effects KW - Cell Aging -- genetics KW - Cell Aging -- drug effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69766181?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Asbestos+induction+of+extended+lifespan+in+normal+human+mesothelial+cells%3A+interindividual+susceptibility+and+SV40+T+antigen.&rft.au=Xu%2C+L%3BFlynn%2C+B+J%3BUngar%2C+S%3BPass%2C+H+I%3BLinnainmaa%2C+K%3BMattson%2C+K%3BGerwin%2C+B+I&rft.aulast=Xu&rft.aufirst=L&rft.date=1999-05-01&rft.volume=20&rft.issue=5&rft.spage=773&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-28 N1 - Date created - 1999-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Multiple organ carcinogenicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344/N rats and B6C3F1 mice and comparison of dose-response with 1,3-butadiene in mice. AN - 69765749; 10334205 AB - Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to 1,3-butadiene, a trans-species carcinogen, inhalation studies were performed with chloroprene to evaluate its carcinogenic potential in rats and mice. Groups of 50 male and female F344/N rats and 50 male and female B6C3F1 mice were exposed to 0, 12.8, 32 or 80 p.p.m. chloroprene (6 h/day, 5 days/week) for 2 years. Under these conditions, chloroprene was carcinogenic to the oral cavity, thyroid gland, lung, kidney and mammary gland of rats, and to the lung, circulatory system (hemangiomas and hemangiosarcomas), Harderian gland, kidney, forestomach, liver, mammary gland, skin, mesentery and Zymbal's gland of mice. Survival adjusted tumor rates in mice were fit to a Weibull model for estimation of the shape of the dose-response curves, estimation of ED10 values (the estimated exposure concentration associated with an increased cancer risk of 10%) and comparison of these parameters with those for 1,3-butadiene. Butadiene has been identified as a potent carcinogen in mice and has been associated with increased risk of lymphatic and hematopoietic cancer in exposed workers. Shape parameter values for most of the neoplastic effects of chloroprene and 1,3-butadiene were consistent with linear or supralinear responses in the area near the lowest tested exposures. The most potent carcinogenic effect of 1,3-butadiene was the induction of lung neoplasms in female mice, which had an ED10 value of 0.3 p.p.m. Since the ED10 value for that same response in chloroprene exposed mice was also 0.3 p.p.m., we conclude that the carcinogenic potency of chloroprene in mice is similar to that of 1,3-butadiene. Cancer potency of chloroprene is greater in the mouse lung than in the rat lung, but greater in the rat kidney than in the mouse kidney and nearly equivalent in the mammary gland of each species. JF - Carcinogenesis AU - Melnick, R L AU - Sills, R C AU - Portier, C J AU - Roycroft, J H AU - Chou, B J AU - Grumbein, S L AU - Miller, R A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. melnickr@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 867 EP - 878 VL - 20 IS - 5 SN - 0143-3334, 0143-3334 KW - Butadienes KW - 0 KW - Carcinogens KW - Chloroprene KW - 126-99-8 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Rats KW - Animals KW - Rats, Inbred F344 KW - Kidney Neoplasms -- chemically induced KW - Dose-Response Relationship, Drug KW - Mice KW - Mammary Neoplasms, Animal -- chemically induced KW - Lung Neoplasms -- chemically induced KW - Administration, Inhalation KW - Species Specificity KW - Male KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Butadienes -- adverse effects KW - Chloroprene -- adverse effects KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69765749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Multiple+organ+carcinogenicity+of+inhaled+chloroprene+%282-chloro-1%2C3-butadiene%29+in+F344%2FN+rats+and+B6C3F1+mice+and+comparison+of+dose-response+with+1%2C3-butadiene+in+mice.&rft.au=Melnick%2C+R+L%3BSills%2C+R+C%3BPortier%2C+C+J%3BRoycroft%2C+J+H%3BChou%2C+B+J%3BGrumbein%2C+S+L%3BMiller%2C+R+A&rft.aulast=Melnick&rft.aufirst=R&rft.date=1999-05-01&rft.volume=20&rft.issue=5&rft.spage=867&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-28 N1 - Date created - 1999-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effect of 26 week magnetic field exposures in a DMBA initiation-promotion mammary gland model in Sprague-Dawley rats. AN - 69765400; 10334209 AB - Several studies have suggested that exposure to 50 Hz magnetic fields promote chemically induced breast cancer in rats. Groups of 100 female Sprague-Dawley rats were initiated with a single 10 mg gavage dose of 7,12-dimethylbenz[a]anthracene (DMBA) at 50 days of age followed by exposure to ambient fields (sham exposed), 50 Hz magnetic fields at either 1 or 5 Gauss (G) field intensity or 60 Hz fields at 1 G for 18.5 h/day, 7 days/week for 26 weeks. A vehicle control group without DMBA was included. Rats were palpated weekly for the presence of tumors. There was no effect of magnetic field exposure on body weight gains or the time of appearance of mammary tumors. At the end of 26 weeks, the animals were killed and the mammary tumors counted and measured. Mammary gland masses found grossly were examined histologically. The mammary gland carcinoma incidence was 96, 90, 95 and 85% (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The total numbers of carcinomas were 649, 494 (P < 0.05, decrease), 547 and 433 (P < 0.05, decrease) for the DMBA controls, 1 G 50 Hz, 5 G 50 Hz and 1 G 60 Hz groups, respectively. The number of fibroadenomas varied from 276 to 319, with the lowest number in the 1 G 60 Hz exposure group. Measurement of the tumors revealed no difference in tumor size between groups. In this breast cancer initiation-promotion study in female Sprague-Dawley rats, there was no evidence that 50 or 60 Hz magnetic fields promoted breast cancer under the conditions of this assay. This study does not support the hypothesis that magnetic field exposure can promote breast cancer in this rat model. JF - Carcinogenesis AU - Boorman, G A AU - Anderson, L E AU - Morris, J E AU - Sasser, L B AU - Mann, P C AU - Grumbein, S L AU - Hailey, J R AU - McNally, A AU - Sills, R C AU - Haseman, J K AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. boorman@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 899 EP - 904 VL - 20 IS - 5 SN - 0143-3334, 0143-3334 KW - Carcinogens KW - 0 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Index Medicus KW - Rats KW - Palpation KW - Animals KW - Rats, Sprague-Dawley KW - Cocarcinogenesis KW - Body Weight -- drug effects KW - Temperature KW - Humidity KW - Disease Models, Animal KW - Time Factors KW - Female KW - 9,10-Dimethyl-1,2-benzanthracene -- adverse effects KW - Electromagnetic Fields -- adverse effects KW - Mammary Neoplasms, Experimental -- etiology KW - Mammary Neoplasms, Experimental -- mortality KW - Mammary Neoplasms, Experimental -- pathology KW - Carcinogens -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69765400?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Effect+of+26+week+magnetic+field+exposures+in+a+DMBA+initiation-promotion+mammary+gland+model+in+Sprague-Dawley+rats.&rft.au=Boorman%2C+G+A%3BAnderson%2C+L+E%3BMorris%2C+J+E%3BSasser%2C+L+B%3BMann%2C+P+C%3BGrumbein%2C+S+L%3BHailey%2C+J+R%3BMcNally%2C+A%3BSills%2C+R+C%3BHaseman%2C+J+K&rft.aulast=Boorman&rft.aufirst=G&rft.date=1999-05-01&rft.volume=20&rft.issue=5&rft.spage=899&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-28 N1 - Date created - 1999-05-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzymatic and nonenzymatic production of free radicals from the carcinogens 4-nitroquinoline N-oxide and 4-hydroxylaminoquinoline N-oxide. AN - 69764193; 10328756 AB - The anion radicals of 4-nitroquinoline N-oxide (4-NQO) and 4-nitrosoquinoline N-oxide (4-NOQO) carcinogens were detected and characterized by electron spin resonance (ESR) spectroscopy. The structures of the radical intermediates were examined by density functional theory (DFT) at the level of hybrid unrestricted uBecke3LYP. The formation of superoxide anion radical catalyzed by flavin-containing enzymes such as cytochrome P450 reductase or xanthine oxidase in the presence of 4-NQO or 4-nitroquinoline N-oxide was studied by spin-trapping experiments. In this case, the ESR signal of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-superoxide radical adduct was observed, and its formation was inhibited by superoxide dismutase (SOD). No ESR signal was detected when the two-electron-transferring flavoenzyme DT-diaphorase (NADPH-quinone oxidoreductase) was used. The above is consistent with a one-electron reduction in the metabolism of these nitro compounds to anion free radicals by various flavoenzyme reductases. JF - Chemical research in toxicology AU - Fann, Y C AU - Metosh-Dickey, C A AU - Winston, G W AU - Sygula, A AU - Rao, D N AU - Kadiiska, M B AU - Mason, R P AD - Free Radical Metabolite Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. fann @niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 450 EP - 458 VL - 12 IS - 5 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Free Radicals KW - Mutagens KW - 4-Hydroxyaminoquinoline-1-oxide KW - 4637-56-3 KW - 4-Nitroquinoline-1-oxide KW - 56-57-5 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Xanthine Oxidase KW - EC 1.17.3.2 KW - NADPH-Ferrihemoprotein Reductase KW - EC 1.6.2.4 KW - NAD(P)H Dehydrogenase (Quinone) KW - EC 1.6.5.2 KW - Index Medicus KW - Electron Spin Resonance Spectroscopy KW - NADPH-Ferrihemoprotein Reductase -- chemistry KW - Superoxide Dismutase -- chemistry KW - NAD(P)H Dehydrogenase (Quinone) -- chemistry KW - Free Radicals -- chemistry KW - Xanthine Oxidase -- chemistry KW - Mutagens -- chemistry KW - 4-Nitroquinoline-1-oxide -- chemistry KW - Carcinogens -- chemistry KW - 4-Hydroxyaminoquinoline-1-oxide -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69764193?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Enzymatic+and+nonenzymatic+production+of+free+radicals+from+the+carcinogens+4-nitroquinoline+N-oxide+and+4-hydroxylaminoquinoline+N-oxide.&rft.au=Fann%2C+Y+C%3BMetosh-Dickey%2C+C+A%3BWinston%2C+G+W%3BSygula%2C+A%3BRao%2C+D+N%3BKadiiska%2C+M+B%3BMason%2C+R+P&rft.aulast=Fann&rft.aufirst=Y&rft.date=1999-05-01&rft.volume=12&rft.issue=5&rft.spage=450&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metabolic activation of 4H-cyclopenta[def]chrysene in human mammary carcinoma MCF-7 cell cultures. AN - 69763154; 10328754 AB - The tumor initiating activities of 4H-cyclopenta[def]chrysene (C[def]C) and its two putative reactive metabolites, trans-1, 2-dihydroxy-anti-3,3a-epoxy-1,2,3, 3a-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-3,3a-DE) and trans-6,7-dihydroxy-anti-8,9-epoxy-6,7,8, 9-tetrahydro-4H-cyclopenta[def]chrysene (C[def]C-8,9-DE), were evaluated previously in mice [Amin, S., et al. (1995) Carcinogenesis 16, 2813-2817]. C[def]C-3,3a-DE was the more active inducer of lung tumors and elicited twice as many tumors as C[def]C-8,9-DE. In this study, the route of metabolism of C[def]C to DNA-reactive metabolites in the human mammary carcinoma cell line (MCF-7) was investigated using the 32P-postlabeling assay. The results show that metabolic activation to DNA-binding species proceeds through the formation of both trans-1,2-dihydrodiol and trans-6,7-dihydrodiol metabolites of C[def]C. At a 1 microM dose, adducts from the methylene-bridged (C[def]C-3,3a-DE) and bay region (C[def]C-8,9-DE) dihydrodiol epoxides were detected in comparable amounts. In contrast, the majority of the postlabeled adducts recovered from cells exposed to a 10 microM dose were derived from the bay region dihydrodiol epoxide, C[def]C-8,9-DE. Using markers from reactions of the dihydrodiol epoxides with deoxyguanosine 3'-phosphate and deoxyadenosine 3'-phosphate, it was shown that the major radioactive spots formed with both anti-C[def]C-3,3a-DE and anti-C[def]C-8,9-DE chromatographed with deoxyguanosine adduct markers. Thus, the human cells used in these studies can activate C[def]C to carcinogenic metabolites. JF - Chemical research in toxicology AU - Agarwal, R AU - Coffing, S L AU - Baird, W M AU - Harvey, R G AU - Dipple, A AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. agarwalr@intra.nci.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 437 EP - 441 VL - 12 IS - 5 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Chrysenes KW - DNA Adducts KW - DNA, Neoplasm KW - Mutagens KW - 4H-cyclopenta(def)chrysen-4-ol KW - 143924-52-1 KW - Index Medicus KW - Animals KW - Tumor Cells, Cultured KW - DNA Adducts -- chemistry KW - Biotransformation KW - Humans KW - Cell Division -- drug effects KW - Mice KW - Chromatography, Thin Layer KW - Autoradiography KW - DNA, Neoplasm -- biosynthesis KW - Female KW - Carcinogens -- metabolism KW - Mutagens -- metabolism KW - Breast Neoplasms -- metabolism KW - Chrysenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69763154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Metabolic+activation+of+4H-cyclopenta%5Bdef%5Dchrysene+in+human+mammary+carcinoma+MCF-7+cell+cultures.&rft.au=Agarwal%2C+R%3BCoffing%2C+S+L%3BBaird%2C+W+M%3BHarvey%2C+R+G%3BDipple%2C+A&rft.aulast=Agarwal&rft.aufirst=R&rft.date=1999-05-01&rft.volume=12&rft.issue=5&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-27 N1 - Date created - 1999-07-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - New vs old fashioned oestradiol antagonists in mammary carcinoma: 'in vitro' and 'in vivo' pharmacological approaches. AN - 69760820; 10328990 AB - The rationale underlying therapeutic strategies designed to inhibit the action of endogenous sex hormones in malignant breast cells is provided by the demonstration of their involvement in supporting the development and growth of breast carcinoma. The surgical removal of steroid-secreting glands, in order to reduce the level of oestrogens reaching their target tissues, has for years been substituted by the so-called endocrinotherapeutic approach, which is based on the counteraction of the steroid hormone activity by the hormonal receptor blockade with suitable antioestrogenic compounds. Over the past 25 years, the non-steroidal oestrogen antagonist tamoxifen has become the standard endocrine treatment for breast cancer. The triphenylethylene-derivative compound competes efficiently for binding to the oestrogen receptor, but the complex retains some transcriptional activity. Consequently, tamoxifen exhibits, both ' in vitro and in vivo ', a range of biological activity from full oestrogen antagonism to partial agonism. There is also evidence suggesting that the agonist activity of this compound may ultimately stimulate breast tumour growth, thus causing some treatment failures. Moreover, the use of tamoxifen is limited by the possible onset of drug-resistance in many patients. Nevertheless, widely tested tamoxifen has proved to be very helpful for the development of new compounds to be used as long-term adjuvant therapy or as preventive agents. These novel oestrogen antagonists belong to two major classes: tamoxifen analogs and new pure steroidal-like antioestrogens. The search for and development of compounds devoid of tamoxifen cross-resistance, with a safer toxicity profile as well as the lack of oestrogenic effects, provide the bases to improve the current therapeutic applications of antioestrogens. Copyright 1999 The Italian Pharmacological Society. JF - Pharmacological research AU - de Cupis, A AU - Schettini, G AU - Favoni, R E AD - National Cancer Institute, Department of Preclinical Oncology, Laboratory of Pharmacology and Neurosciences, Genoa, Italy. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 335 EP - 344 VL - 39 IS - 5 SN - 1043-6618, 1043-6618 KW - Antineoplastic Agents, Hormonal KW - 0 KW - Estrogen Antagonists KW - Receptors, Estrogen KW - Tamoxifen KW - 094ZI81Y45 KW - Index Medicus KW - Receptors, Estrogen -- antagonists & inhibitors KW - Tamoxifen -- pharmacology KW - Animals KW - Tamoxifen -- therapeutic use KW - Humans KW - Clinical Trials as Topic KW - Receptors, Estrogen -- agonists KW - Female KW - Breast Neoplasms -- drug therapy KW - Estrogen Antagonists -- pharmacology KW - Antineoplastic Agents, Hormonal -- pharmacology KW - Breast Neoplasms -- prevention & control KW - Estrogen Antagonists -- therapeutic use KW - Antineoplastic Agents, Hormonal -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69760820?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=New+vs+old+fashioned+oestradiol+antagonists+in+mammary+carcinoma%3A+%27in+vitro%27+and+%27in+vivo%27+pharmacological+approaches.&rft.au=de+Cupis%2C+A%3BSchettini%2C+G%3BFavoni%2C+R+E&rft.aulast=de+Cupis&rft.aufirst=A&rft.date=1999-05-01&rft.volume=39&rft.issue=5&rft.spage=335&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=10436618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-03 N1 - Date created - 1999-08-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Pharmacol Res. 1999 May;39(5):333 [10328989] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonrandom breakpoints of unbalanced chromosome translocations in human hepatocellular carcinoma cell lines. AN - 69760086; 10326589 AB - In the search for specific chromosomal alterations in human hepatocellular carcinomas (HCC), we analyzed two new HCC cell lines and identified nonrandom changes by combined G-banding and fluorescence in situ hybridization (FISH). Cell line 7703 was established from an HCC deriving from a patient in the Qidong region of China, where the incidence of HCC is very high and is associated with hepatitis-B virus infection and exposure to aflatoxin. This line has a highly rearranged karyotype eliciting complex rearrangements involving the majority of chromosomes. The second line, SK-Hep-1, derived from a liver adenocarcinoma, is less heterogeneous, having few altered chromosomes. We have characterized the majority of structural and numerical alterations and identified in both lines unbalanced translocations with the breakpoints nonrandomly involving regions 1p36 and 3p14 and gain of chromosome 6p and 8q. While gain of 6p and 8q are recurrent in HCC, translocations of 1p and 3p are described for the first time. Damage and recombination at the breakpoint sites on chromosomes 1 and 3 might have resulted in activation of proto-oncogene, formation of new oncogenic chimeric genes, or loss of tumor suppressor genes. JF - Cancer genetics and cytogenetics AU - Keck, C L AU - Zimonjic, D B AU - Yuan, B Z AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 37 EP - 44 VL - 111 IS - 1 SN - 0165-4608, 0165-4608 KW - Index Medicus KW - Karyotyping KW - Chromosomes, Human, Pair 1 KW - Chromosomes, Human, Pair 3 KW - Tumor Cells, Cultured KW - Humans KW - In Situ Hybridization, Fluorescence KW - Carcinoma, Hepatocellular -- genetics KW - Translocation, Genetic KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69760086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+genetics+and+cytogenetics&rft.atitle=Nonrandom+breakpoints+of+unbalanced+chromosome+translocations+in+human+hepatocellular+carcinoma+cell+lines.&rft.au=Keck%2C+C+L%3BZimonjic%2C+D+B%3BYuan%2C+B+Z%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Keck&rft.aufirst=C&rft.date=1999-05-01&rft.volume=111&rft.issue=1&rft.spage=37&rft.isbn=&rft.btitle=&rft.title=Cancer+genetics+and+cytogenetics&rft.issn=01654608&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-26 N1 - Date created - 1999-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide. AN - 69759272; 10329967 AB - We have developed a cellular model in which cultured astrocytes and brain capillary endothelial cells preconditioned with tumor necrosis factor-alpha (TNF-alpha) fail to upregulate intercellular adhesion molecule-1 (ICAM-1) protein (80% inhibition) and mRNA (30% inhibition) when challenged with TNF-alpha or exposed to hypoxia. Inasmuch as ceramide is known to mediate some of the effects of TNF-alpha, its levels were measured at various times after the TNF-alpha preconditioning. We present evidence for the first time that, in normal brain cells, TNF-alpha pretreatment causes a biphasic increase of ceramide levels: an early peak at 15-20 min, when ceramide levels increased 1.9-fold in astrocytes and 2.7-fold in rat brain capillary endothelial cells, and a delayed 2- to 3-fold ceramide increase that occurs 18-24 h after addition of TNF-alpha. The following findings indicate that the delayed ceramide accumulation results in cell unresponsiveness to TNF-alpha: 1) coincident timing of the ceramide peak and the tolerance period, 2) mimicking of preconditioning by addition of exogenous ceramide, and 3) attenuation of preconditioning by fumonisin B1, an inhibitor of ceramide synthesis. In contrast to observations in transformed cell lines, the delayed ceramide increase was transient and did not induce apoptosis in brain cells. JF - The American journal of physiology AU - Ginis, I AU - Schweizer, U AU - Brenner, M AU - Liu, J AU - Azzam, N AU - Spatz, M AU - Hallenbeck, J M AD - Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. ginis@codon.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - C1171 EP - C1183 VL - 276 IS - 5 Pt 1 SN - 0002-9513, 0002-9513 KW - Carboxylic Acids KW - 0 KW - Ceramides KW - Fumonisins KW - RNA, Messenger KW - Tumor Necrosis Factor-alpha KW - Intercellular Adhesion Molecule-1 KW - 126547-89-5 KW - fumonisin B1 KW - 3ZZM97XZ32 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Endothelium, Vascular -- metabolism KW - Apoptosis KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Gene Expression KW - Carboxylic Acids -- pharmacology KW - Oxygen -- administration & dosage KW - Intercellular Adhesion Molecule-1 -- genetics KW - Capillaries KW - Intercellular Adhesion Molecule-1 -- metabolism KW - Astrocytes -- metabolism KW - Brain -- cytology KW - Brain -- blood supply KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Ceramides -- antagonists & inhibitors KW - Brain -- metabolism KW - Ceramides -- physiology KW - Cell Hypoxia KW - Ceramides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69759272?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=TNF-alpha+pretreatment+prevents+subsequent+activation+of+cultured+brain+cells+with+TNF-alpha+and+hypoxia+via+ceramide.&rft.au=Ginis%2C+I%3BSchweizer%2C+U%3BBrenner%2C+M%3BLiu%2C+J%3BAzzam%2C+N%3BSpatz%2C+M%3BHallenbeck%2C+J+M&rft.aulast=Ginis&rft.aufirst=I&rft.date=1999-05-01&rft.volume=276&rft.issue=5+Pt+1&rft.spage=C1171&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bacteriophage T4 rnh (RNase H) null mutations: effects on spontaneous mutation and epistatic interaction with rII mutations. AN - 69745246; 10322013 AB - The bacteriophage T4 rnh gene encodes T4 RNase H, a relative of a family of flap endonucleases. T4 rnh null mutations reduce burst sizes, increase sensitivity to DNA damage, and increase the frequency of acriflavin resistance (Acr) mutations. Because mutations in the related Saccharomyces cerevisiae RAD27 gene display a remarkable duplication mutator phenotype, we further explored the impact of rnh mutations upon the mutation process. We observed that most Acr mutants in an rnh+ strain contain ac mutations, whereas only roughly half of the Acr mutants detected in an rnhDelta strain bear ac mutations. In contrast to the mutational specificity displayed by most mutators, the DNA alterations of ac mutations arising in rnhDelta and rnh+ backgrounds are indistinguishable. Thus, the increase in Acr mutants in an rnhDelta background is probably not due to a mutator effect. This conclusion is supported by the lack of increase in the frequency of rI mutations in an rnhDelta background. In a screen that detects mutations at both the rI locus and the much larger rII locus, the r frequency was severalfold lower in an rnhDelta background. This decrease was due to the phenotype of rnh rII double mutants, which display an r+ plaque morphology but retain the characteristic inability of rII mutants to grow on lambda lysogens. Finally, we summarize those aspects of T4 forward-mutation systems which are relevant to optimal choices for investigating quantitative and qualitative aspects of the mutation process. JF - Journal of bacteriology AU - Bebenek, A AU - Smith, L A AU - Drake, J W AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 3123 EP - 3128 VL - 181 IS - 10 SN - 0021-9193, 0021-9193 KW - Viral Proteins KW - 0 KW - rIIA protein, Enterobacteria phage T4 KW - Acriflavine KW - 1T3A50395T KW - Ribonuclease H KW - EC 3.1.26.4 KW - Index Medicus KW - Viral Proteins -- genetics KW - Phenotype KW - Base Sequence KW - Acriflavine -- pharmacology KW - Gene Frequency KW - Kinetics KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Drug Resistance, Microbial KW - Mutation KW - Mutagenesis -- drug effects KW - Bacteriophage T4 -- enzymology KW - Genes, Viral -- genetics KW - Bacteriophage T4 -- growth & development KW - Bacteriophage T4 -- genetics KW - Ribonuclease H -- genetics KW - Ribonuclease H -- metabolism KW - Epistasis, Genetic KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69745246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+bacteriology&rft.atitle=Bacteriophage+T4+rnh+%28RNase+H%29+null+mutations%3A+effects+on+spontaneous+mutation+and+epistatic+interaction+with+rII+mutations.&rft.au=Bebenek%2C+A%3BSmith%2C+L+A%3BDrake%2C+J+W&rft.aulast=Bebenek&rft.aufirst=A&rft.date=1999-05-01&rft.volume=181&rft.issue=10&rft.spage=3123&rft.isbn=&rft.btitle=&rft.title=Journal+of+bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-17 N1 - Date created - 1999-06-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Genetics. 1991 Mar;127(3):453-62 [1849858] J Biol Chem. 1991 Jan 25;266(3):1888-97 [1703156] Genetics. 1994 Nov;138(3):553-64 [7851754] Science. 1995 Jul 14;269(5221):238-40 [7618086] Cell. 1996 Jun 28;85(7):1101-12 [8674116] Genetics. 1996 Jul;143(3):1081-90 [8807283] J Bacteriol. 1996 Dec;178(23):6772-7 [8955295] Cell. 1997 Jan 24;88(2):253-63 [9008166] J Biol Chem. 1997 Nov 7;272(45):28523-30 [9353314] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] Genetics. 1998 Apr;148(4):1539-50 [9560373] Genetics. 1998 Apr;148(4):1655-65 [9560385] Trends Biochem Sci. 1998 May;23(5):171-3 [9612080] Nat Struct Biol. 1998 Aug;5(8):707-13 [9699635] Cell. 1998 Oct 2;95(1):135-46 [9778254] Nucleic Acids Res. 1998 Dec 15;26(24):5589-95 [9837987] J Mol Biol. 1961 Dec;3:762-8 [14482221] Proc Natl Acad Sci U S A. 1965 Jan;53:24-30 [14283203] Cold Spring Harb Symp Quant Biol. 1966;31:77-84 [5237214] Genetics. 1970 Jul;65(3):379-90 [4933467] Genetics. 1984 Aug;107(4):505-23 [6745639] J Mol Biol. 1988 Apr 20;200(4):665-80 [2842508] J Mol Biol. 1993 Jan 5;229(1):8-13 [8421317] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Progressive multifocal leukoencephalopathy and JC virus genotypes in West African patients with acquired immunodeficiency syndrome: a pathologic and DNA sequence analysis of 4 cases. AN - 69739264; 10235497 AB - Progressive multifocal leukoencephalopathy is caused by polyomavirus JC in immunosuppressed patients. JC virus genotypes are identified by sequence analysis of the viral genome. Despite the prevalence of acquired immunodeficiency syndrome in sub-Saharan Africa, few cases of progressive multifocal leukoencephalopathy have been reported from this region. Here we describe 4 African cases and provide an analysis of viral genotypes. Immunohistochemical staining by labeled streptavidin-biotin for capsid protein antigen was performed on all cases. Polymerase chain reaction amplification of viral genomic DNA was followed by direct cycle sequencing. JC virus type 3 was identified in 2 cases, and type 6 was isolated in 1 case. The viral regulatory region from 1 case showed an uncommon rearrangement pattern. Progressive multifocal leukoencephalopathy in West African patients with acquired immunodeficiency syndrome is caused by African genotypes of JC virus (types 3 and 6). The prevalence of disease in this autopsy series from sub-Saharan Africa (1.5%) was less than has been reported from Europe and the United States (4% to 10%) and may be partly due to biological differences in JC virus genotypes. Further studies will be needed to confirm this observation. JF - Archives of pathology & laboratory medicine AU - Chima, S C AU - Agostini, H T AU - Ryschkewitsch, C F AU - Lucas, S B AU - Stoner, G L AD - Neurotoxicology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-4126, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 395 EP - 403 VL - 123 IS - 5 SN - 0003-9985, 0003-9985 KW - DNA, Viral KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Polymorphism, Genetic KW - Humans KW - Genotype KW - Polymerase Chain Reaction KW - Base Sequence KW - DNA, Viral -- analysis KW - Adult KW - Molecular Sequence Data KW - Africa KW - Middle Aged KW - Immunohistochemistry KW - Female KW - Male KW - Acquired Immunodeficiency Syndrome -- genetics KW - Leukoencephalopathy, Progressive Multifocal -- virology KW - JC Virus -- genetics KW - Leukoencephalopathy, Progressive Multifocal -- pathology KW - Brain -- pathology KW - Brain -- virology KW - Leukoencephalopathy, Progressive Multifocal -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69739264?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+pathology+%26+laboratory+medicine&rft.atitle=Progressive+multifocal+leukoencephalopathy+and+JC+virus+genotypes+in+West+African+patients+with+acquired+immunodeficiency+syndrome%3A+a+pathologic+and+DNA+sequence+analysis+of+4+cases.&rft.au=Chima%2C+S+C%3BAgostini%2C+H+T%3BRyschkewitsch%2C+C+F%3BLucas%2C+S+B%3BStoner%2C+G+L&rft.aulast=Chima&rft.aufirst=S&rft.date=1999-05-01&rft.volume=123&rft.issue=5&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Archives+of+pathology+%26+laboratory+medicine&rft.issn=00039985&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic deletion of p21WAF1 enhances papilloma formation but not malignant conversion in experimental mouse skin carcinogenesis. AN - 69736937; 10232585 AB - Tumor suppression by p53 is believed to reside in its ability to regulate gene transcription, including up-regulation of p21WAF1. In p53(-/-) mice, chemical- or oncogene-induced skin tumors undergo accelerated malignant conversion. To determine the contribution of the p21WAF1 gene product to epidermal carcinogenesis, animals +/+, +/-, and -/- for a null mutation in the p21WAF1 gene were treated once with 25 nmol 7,12-dimethylbenz[a]anthracene, followed by 5 microg of TPA two times/week for 20 weeks. Papilloma frequency was higher in the p21WAF1-deficient mice. However, the frequency of malignant conversion was similar among all three genotypes. After TPA treatment, all genotypes developed epidermal hyperplasia, although the labeling index was lower in p21WAF1 (-/-) epidermis compared with p21WAF1 (+/+). Furthermore, the expression of differentiation markers was the same across genotypes in untreated or TPA-treated epidermis. Similar frequencies of malignant conversion were also observed in an in vitro assay. Thus, p21WAF1 suppresses early stages of papilloma formation but not malignant progression in mouse skin carcinogenesis, and decreased levels of p21WAF1 do not account for the enhanced malignant conversion of p53 null epidermal tumors. JF - Cancer research AU - Weinberg, W C AU - Fernandez-Salas, E AU - Morgan, D L AU - Shalizi, A AU - Mirosh, E AU - Stanulis, E AU - Deng, C AU - Hennings, H AU - Yuspa, S H AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4340, USA. wweinberg@yoda.nidr.nih.gov Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 2050 EP - 2054 VL - 59 IS - 9 SN - 0008-5472, 0008-5472 KW - Antigens, Differentiation KW - 0 KW - Biomarkers KW - Carcinogens KW - Cdkn1a protein, mouse KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - Tumor Suppressor Protein p53 KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Tumor Suppressor Protein p53 -- physiology KW - Cocarcinogenesis KW - Antigens, Differentiation -- analysis KW - Cell Division -- drug effects KW - Disease Progression KW - Mice KW - Mice, Knockout KW - Genotype KW - Hyperplasia KW - Epidermis -- drug effects KW - Genes, p53 KW - Mitotic Index KW - Epidermis -- pathology KW - Tumor Suppressor Protein p53 -- deficiency KW - Skin Neoplasms -- genetics KW - Cyclins -- physiology KW - Cyclins -- deficiency KW - Skin Neoplasms -- chemically induced KW - Carcinoma, Squamous Cell -- genetics KW - Carcinoma, Squamous Cell -- chemically induced KW - Papilloma -- genetics KW - Papilloma -- chemically induced KW - Cyclins -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69736937?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Genetic+deletion+of+p21WAF1+enhances+papilloma+formation+but+not+malignant+conversion+in+experimental+mouse+skin+carcinogenesis.&rft.au=Weinberg%2C+W+C%3BFernandez-Salas%2C+E%3BMorgan%2C+D+L%3BShalizi%2C+A%3BMirosh%2C+E%3BStanulis%2C+E%3BDeng%2C+C%3BHennings%2C+H%3BYuspa%2C+S+H&rft.aulast=Weinberg&rft.aufirst=W&rft.date=1999-05-01&rft.volume=59&rft.issue=9&rft.spage=2050&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors. AN - 69733993; 10232612 AB - Arachidonic acid (AA) metabolizing enzymes are emerging as significant mediators of growth stimulation for epithelial cells. The relative contribution of the various family members of AA metabolizing enzymes to epithelial cancer cell growth is not known. To study this question, we first analyzed a series of epithelial cancer cells to establish the relative frequency of expression for the various enzymes. We analyzed the expression of five AA metabolizing enzymes as well as 5-lipoxygenase activating protein (FLAP) in a panel of human epithelial cancer cell lines (n = 20) using reverse transcription-PCR. From this analysis, we found that cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), and FLAP were universally expressed in all cancer cell lines tested. For the remaining enzymes, the expression of COX-2, 12-LOX, and 15-LOX varied among cell lines, 60, 35, and 90%, respectively. Although the pattern of expression varied among the different cell types, all of the enzymes were expressed in all major cancer histologies. Using a panel of selective biochemical AA metabolizing enzyme inhibitors, we then evaluated the effect of these agents on cell lines with known expression status for the AA metabolizing enzymes. For the enzymes that were not universally expressed, growth inhibition by selective biochemical inhibitors did not closely correlate with the expression status of specific enzymes (P > 0.05). For the universally expressed enzymes, the LOX inhibitors were more potent growth inhibitors than the COX inhibitors. The frequent expression of the AA metabolizing enzymes suggests that AA metabolism pathway may be modulated in response to xenobiotic exposure during carcinogenesis. Although establishing a priori AA metabolizing enzyme status was not consistently informative about what AA metabolizing enzyme inhibition would be most growth inhibitory, the frequent inhibition of many epithelial cancers by these biochemical inhibitors opens a new avenue for cancer therapy and intervention in carcinogenesis. JF - Cancer research AU - Hong, S H AU - Avis, I AU - Vos, M D AU - Martínez, A AU - Treston, A M AU - Mulshine, J L AD - Intervention Section, Cell and Cancer Biology Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892-1906, USA. Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 2223 EP - 2228 VL - 59 IS - 9 SN - 0008-5472, 0008-5472 KW - 5-Lipoxygenase-Activating Proteins KW - 0 KW - ALOX5AP protein, human KW - Carrier Proteins KW - Cyclooxygenase 2 Inhibitors KW - Cyclooxygenase Inhibitors KW - Growth Inhibitors KW - Isoenzymes KW - Lipoxygenase Inhibitors KW - Membrane Proteins KW - Neoplasm Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Arachidonic Acid KW - 27YG812J1I KW - Arachidonate 12-Lipoxygenase KW - EC 1.13.11.31 KW - Arachidonate 5-Lipoxygenase KW - EC 1.13.11.34 KW - Cyclooxygenase 1 KW - EC 1.14.99.1 KW - Cyclooxygenase 2 KW - PTGS1 protein, human KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - RNA, Neoplasm -- biosynthesis KW - Lung Neoplasms -- enzymology KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Tumor Cells, Cultured -- enzymology KW - RNA, Messenger -- biosynthesis KW - Prostatic Neoplasms -- pathology KW - Enzyme Induction -- drug effects KW - Breast Neoplasms -- pathology KW - Colonic Neoplasms -- pathology KW - Male KW - Drug Screening Assays, Antitumor KW - Cell Division -- drug effects KW - Colonic Neoplasms -- enzymology KW - Signal Transduction -- physiology KW - Signal Transduction -- drug effects KW - Arachidonate 12-Lipoxygenase -- metabolism KW - Prostatic Neoplasms -- enzymology KW - Breast Neoplasms -- enzymology KW - Female KW - Lung Neoplasms -- pathology KW - Carrier Proteins -- metabolism KW - Neoplasm Proteins -- antagonists & inhibitors KW - Carrier Proteins -- antagonists & inhibitors KW - Membrane Proteins -- metabolism KW - Arachidonic Acid -- metabolism KW - Isoenzymes -- metabolism KW - Cyclooxygenase Inhibitors -- pharmacology KW - Arachidonate 5-Lipoxygenase -- metabolism KW - Epithelial Cells -- drug effects KW - Epithelial Cells -- enzymology KW - Carcinoma -- pathology KW - Prostaglandin-Endoperoxide Synthases -- metabolism KW - Lipoxygenase Inhibitors -- pharmacology KW - Growth Inhibitors -- pharmacology KW - Carcinoma -- enzymology KW - Membrane Proteins -- antagonists & inhibitors KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69733993?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Relationship+of+arachidonic+acid+metabolizing+enzyme+expression+in+epithelial+cancer+cell+lines+to+the+growth+effect+of+selective+biochemical+inhibitors.&rft.au=Hong%2C+S+H%3BAvis%2C+I%3BVos%2C+M+D%3BMart%C3%ADnez%2C+A%3BTreston%2C+A+M%3BMulshine%2C+J+L&rft.aulast=Hong&rft.aufirst=S&rft.date=1999-05-01&rft.volume=59&rft.issue=9&rft.spage=2223&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antipsychotics in children and adolescents. AN - 69730337; 10230185 AB - To present a critical overview of the available evidence for the efficacy and safety of antipsychotic agents in children and adolescents and to identify knowledge gaps and needs for further research. Data from adults that are relevant to children are discussed. Mainly reports of double-blind, placebo-controlled studies were reviewed. In children and adolescents, antipsychotics are used to treat psychotic and a variety of nonpsychotic conditions. The amount of data based on well-designed, double-blind, placebo-controlled studies with satisfactory sample sizes in diagnostically homogeneous subjects is modest. Currently available standard antipsychotics have a definite role in the treatment of children and adolescents. The use of these agents is limited mainly by tardive and withdrawal dyskinesias and, in some patients, by excessive sedation. The atypical antipsychotics should be critically assessed and compared with psychosocial interventions; if effective, the combination of both types of treatments should be evaluated. JF - Journal of the American Academy of Child and Adolescent Psychiatry AU - Campbell, M AU - Rapoport, J L AU - Simpson, G M AD - Child Psychiatry Branch, NIMH, Bethesda, MD, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 537 EP - 545 VL - 38 IS - 5 SN - 0890-8567, 0890-8567 KW - Antipsychotic Agents KW - 0 KW - Index Medicus KW - Humans KW - Adolescent Psychiatry -- trends KW - Treatment Outcome KW - Clinical Trials as Topic KW - Child KW - Adolescent KW - Research Design KW - Child Psychiatry -- trends KW - Antipsychotic Agents -- therapeutic use KW - Antipsychotic Agents -- pharmacokinetics KW - Antipsychotic Agents -- adverse effects KW - Psychotic Disorders -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69730337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.atitle=Antipsychotics+in+children+and+adolescents.&rft.au=Campbell%2C+M%3BRapoport%2C+J+L%3BSimpson%2C+G+M&rft.aulast=Campbell&rft.aufirst=M&rft.date=1999-05-01&rft.volume=38&rft.issue=5&rft.spage=537&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Academy+of+Child+and+Adolescent+Psychiatry&rft.issn=08908567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-25 N1 - Date created - 1999-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Genetic factors affecting the impact of DNA polymerase delta proofreading activity on mutation avoidance in yeast. AN - 69724293; 10224242 AB - Base selectivity, proofreading, and postreplication mismatch repair are important for replication fidelity. Because proofreading plays an important role in error correction, we have investigated factors that influence its impact in the yeast Saccharomyces cerevisiae. We have utilized a sensitive mutation detection system based on homonucleotide runs of 4 to 14 bases to examine the impact of DNA polymerase delta proofreading on mutation avoidance. The contribution of DNA polymerase delta proofreading on error avoidance was found to be similar to that of DNA polymerase epsilon proofreading in short homonucleotide runs (A4 and A5) but much greater than the contribution of DNA polymerase epsilon proofreading in longer runs. We have identified an intraprotein interaction affecting mutation prevention that results from mutations in the replication and the proofreading regions, resulting in an antimutator phenotype relative to a proofreading defect. Finally, a diploid strain with a defect in DNA polymerase delta proofreading exhibits a higher mutation rate than a haploid strain. We suggest that in the diploid population of proofreading defective cells there exists a transiently hypermutable fraction that would be inviable if cells were haploids. JF - Genetics AU - Tran, H T AU - Degtyareva, N P AU - Gordenin, D A AU - Resnick, M A AD - Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 47 EP - 59 VL - 152 IS - 1 SN - 0016-6731, 0016-6731 KW - Recombinant Fusion Proteins KW - 0 KW - DNA Polymerase III KW - EC 2.7.7.- KW - Index Medicus KW - Phenotype KW - Frameshift Mutation KW - Base Sequence KW - DNA Repair KW - Haploidy KW - Models, Genetic KW - DNA Mutational Analysis KW - Molecular Sequence Data KW - Mutagenesis KW - Diploidy KW - Saccharomyces cerevisiae -- genetics KW - DNA Polymerase III -- physiology KW - DNA Polymerase III -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69724293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genetics&rft.atitle=Genetic+factors+affecting+the+impact+of+DNA+polymerase+delta+proofreading+activity+on+mutation+avoidance+in+yeast.&rft.au=Tran%2C+H+T%3BDegtyareva%2C+N+P%3BGordenin%2C+D+A%3BResnick%2C+M+A&rft.aulast=Tran&rft.aufirst=H&rft.date=1999-05-01&rft.volume=152&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Genetics&rft.issn=00166731&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-12 N1 - Date created - 1999-07-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Cold Spring Harb Symp Quant Biol. 1966;31:77-84 [5237214] Annu Rev Biochem. 1996;65:101-33 [8811176] J Biol Chem. 1988 Oct 15;263(29):14784-9 [3049589] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] EMBO J. 1989 Jun;8(6):1849-54 [2670563] J Biol Chem. 1991 Mar 15;266(8):5055-61 [2002048] J Biol Chem. 1991 Apr 5;266(10):6336-41 [2007586] EMBO J. 1991 Aug;10(8):2165-70 [1648480] Yeast. 1991 Apr;7(3):253-63 [1882550] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] Nucleic Acids Res. 1992 Jan 25;20(2):375 [1741270] EMBO J. 1992 Feb;11(2):733-40 [1537345] Genetics. 1992 Dec;132(4):975-85 [1334021] EMBO J. 1993 Apr;12(4):1467-73 [8385605] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5613-7 [8516308] Mol Cell Biol. 1993 Sep;13(9):5315-22 [8395002] Genetics. 1993 Aug;134(4):1023-30 [8375645] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6830-4 [8041704] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4 [7937876] Genetics. 1996 Aug;143(4):1579-87 [8844147] Genetics. 1996 Mar;142(3):717-26 [8849882] Mol Cell Biol. 1997 Feb;17(2):1027-36 [9001255] Mol Cell Biol. 1997 May;17(5):2851-8 [9111357] Mol Cell Biol. 1997 May;17(5):2859-65 [9111358] Biol Chem. 1997 May;378(5):345-62 [9191022] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5 [9618505] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8739-43 [9671748] Mutat Res. 1998 May 25;400(1-2):45-58 [9685581] Mol Cell Biol. 1999 Mar;19(3):2000-7 [10022887] Mol Cell Biol. 1999 Apr;19(4):3177-83 [10082584] Yeast. 1994 Dec;10(13):1793-808 [7747518] Science. 1995 Jul 14;269(5221):238-40 [7618086] Cancer Res. 1995 Oct 15;55(20):4525-30 [7553621] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] J Bacteriol. 1995 Oct;177(20):5979-86 [7592352] Nat Med. 1995 Jul;1(7):686-92 [7585152] Biochemistry. 1996 Jan 23;35(3):1046-53 [8547240] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2856-61 [8610131] Mutat Res. 1996 Jul 10;369(1-2):33-44 [8700180] J Biol Chem. 1979 Mar 10;254(5):1748-53 [368075] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of 3,3',4,4'-tetrachloroazoxybenzene in rats and mice. AN - 69722648; 10222313 AB - The toxicity of 3,3',4,4'-tetrachloroazoxybenzene (TCAOB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and effects on sperm morphology and estrous cycle length. Groups of 10 rats and 10 mice of each sex were exposed to TCAOB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg 5 days a week for 13 weeks. In the rat studies, the major effects included death in the 30 mg TCAOB/kg dose group; at lower exposure levels, a decrease in body weight gain, a decrease in thymus weight, an increase in liver weight, an increase in hematopoietic cell proliferation in the spleen and liver, a responsive anemia, a decrease in platelet counts, a chronic active inflammation of the vasculature in the lung, an increase in cardiomyopathy, hyperplasia of the forestomach, and a marked decrease in circulating thyroxine concentrations were observed. In male rats a decrease in sperm motility in the epididymides was observed. In addition, in female rats an increase in lung, spleen, kidney, and heart weights and nephropathy was observed. Furthermore, the estrous cycle length was increased. In the mouse studies, the major effects for males and females included a decrease in thymus weights, an increase in liver and kidney weights, centrilobular hypertrophy in the liver, hematopoietic cell proliferation, hyperplasia of the forestomach, and dilatation of hair follicles. The spectrum of effects in both rats and mice after exposure to TCAOB indicates that dioxin-like effects occur in addition to effects that have not been observed with dioxin-like compounds. No no-observed-adverse-effect level was reached in male or female rats or mice. Copyright 1999 Academic Press. JF - Toxicology and applied pharmacology AU - van Birgelen, A P AU - Hébert, C D AU - Wenk, M L AU - Grimes, L K AU - Chapin, R E AU - Travlos, G S AU - Mahler, J AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. VANBIRGE@NIEHS.NIH.GOV Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 206 EP - 221 VL - 156 IS - 3 SN - 0041-008X, 0041-008X KW - Azo Compounds KW - 0 KW - Environmental Pollutants KW - Thyroid Hormones KW - 3,4,3',4'-tetrachloroazoxybenzene KW - 21232-47-3 KW - Index Medicus KW - Animals KW - Reproduction -- drug effects KW - Mice KW - Estrus -- drug effects KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Spermatozoa -- drug effects KW - Body Weight -- drug effects KW - Thyroid Hormones -- blood KW - Species Specificity KW - Female KW - Male KW - Spermatozoa -- ultrastructure KW - Organ Size -- drug effects KW - Environmental Pollutants -- toxicity KW - Azo Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69722648?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Toxicity+of+3%2C3%27%2C4%2C4%27-tetrachloroazoxybenzene+in+rats+and+mice.&rft.au=van+Birgelen%2C+A+P%3BH%C3%A9bert%2C+C+D%3BWenk%2C+M+L%3BGrimes%2C+L+K%3BChapin%2C+R+E%3BTravlos%2C+G+S%3BMahler%2C+J%3BBucher%2C+J+R&rft.aulast=van+Birgelen&rft.aufirst=A&rft.date=1999-05-01&rft.volume=156&rft.issue=3&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus. AN - 69718970; 10223460 AB - Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity). Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging-guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals). Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience. JF - Journal of neurosurgery AU - Lieberman, D M AU - Corthesy, M E AU - Cummins, A AU - Oldfield, E H AD - Central Nervous System Implantation Unit, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 928 EP - 934 VL - 90 IS - 5 SN - 0022-3085, 0022-3085 KW - Ibotenic Acid KW - 2552-55-8 KW - Kainic Acid KW - SIV03811UC KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Infusions, Intra-Arterial KW - Feasibility Studies KW - Macaca mulatta KW - Infusions, Parenteral KW - Drug Evaluation, Preclinical KW - Stereotaxic Techniques KW - Parkinson Disease, Secondary -- chemically induced KW - Ibotenic Acid -- therapeutic use KW - MPTP Poisoning KW - Kainic Acid -- therapeutic use KW - Globus Pallidus -- drug effects KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69718970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurosurgery&rft.atitle=Reversal+of+experimental+parkinsonism+by+using+selective+chemical+ablation+of+the+medial+globus+pallidus.&rft.au=Lieberman%2C+D+M%3BCorthesy%2C+M+E%3BCummins%2C+A%3BOldfield%2C+E+H&rft.aulast=Lieberman&rft.aufirst=D&rft.date=1999-05-01&rft.volume=90&rft.issue=5&rft.spage=928&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurosurgery&rft.issn=00223085&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-19 N1 - Date created - 1999-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-linked glycosylation is required for optimal AT1a angiotensin receptor expression in COS-7 cells. AN - 69718298; 10218949 AB - The nature and role of glycosylation in AT1 angiotensin receptor (AT1-R) function were investigated by expressing glycosylation-deficient influenza hemagglutinin (HA) epitope-tagged rat AT1a-Rs (HA-AT1a-Rs) in COS-7 cells. All three asparagine residues (Asn4, Asn176, Asn188) contained within consensus sites for N-linked glycosylation could be glycosylated in Cos-7 cells and appeared to be glycosylated on the endogenous AT1-R in bovine adrenal glomerulosa cells. Heterogeneity of glycosylation at each site accounted for the broad migration pattern of the AT1-R in SDS-PAGE. Mutation at each glycosylation site, either alone or in combination, had little effect on ligand binding parameters (although the N4K mutant had higher affinity) or signaling activity. However, an increasing number of mutated glycosylation sites was associated with decreasing cell surface receptor expression, which was minimal for the unglycosylated N4K/N176Q/N188Q receptor. Decreased surface expression of mutant HA-AT1a-Rs was correlated with decreased total cell receptor content as revealed by immunoblotting with an anti-HA antibody. These findings suggest that glycosylation enhances receptor stability, possibly by protecting nascent receptors from proteolytic degradation. JF - Endocrinology AU - Jayadev, S AU - Smith, R D AU - Jagadeesh, G AU - Baukal, A J AU - Hunyady, L AU - Catt, K J AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2010 EP - 2017 VL - 140 IS - 5 SN - 0013-7227, 0013-7227 KW - Affinity Labels KW - 0 KW - Inositol Phosphates KW - Iodine Radioisotopes KW - Receptor, Angiotensin, Type 1 KW - Receptors, Angiotensin KW - Angiotensin II KW - 11128-99-7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Immunoblotting KW - COS Cells KW - Electrophoresis, Polyacrylamide Gel KW - Inositol Phosphates -- metabolism KW - Glycosylation KW - Structure-Activity Relationship KW - Mutagenesis KW - Rats KW - Angiotensin II -- metabolism KW - Cattle KW - Kinetics KW - Carbohydrate Conformation KW - Receptors, Angiotensin -- chemistry KW - Receptors, Angiotensin -- metabolism KW - Receptors, Angiotensin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69718298?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Endocrinology&rft.atitle=N-linked+glycosylation+is+required+for+optimal+AT1a+angiotensin+receptor+expression+in+COS-7+cells.&rft.au=Jayadev%2C+S%3BSmith%2C+R+D%3BJagadeesh%2C+G%3BBaukal%2C+A+J%3BHunyady%2C+L%3BCatt%2C+K+J&rft.aulast=Jayadev&rft.aufirst=S&rft.date=1999-05-01&rft.volume=140&rft.issue=5&rft.spage=2010&rft.isbn=&rft.btitle=&rft.title=Endocrinology&rft.issn=00137227&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. AN - 69716246; 10213916 AB - Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. JF - Neuroimmunomodulation AU - Torpy, D J AU - Webster, E L AU - Zachman, E K AU - Aguilera, G AU - Chrousos, G P AD - Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892-1862, USA. TorpyD@cc1.nichd.nih.gov PY - 1999 SP - 182 EP - 186 VL - 6 IS - 3 SN - 1021-7401, 1021-7401 KW - Anti-Inflammatory Agents, Non-Steroidal KW - 0 KW - CRF receptor type 2 KW - Receptors, Corticotropin-Releasing Hormone KW - Urocortins KW - Hydralazine KW - 26NAK24LS8 KW - Carrageenan KW - 9000-07-1 KW - Corticotropin-Releasing Hormone KW - 9015-71-8 KW - Index Medicus KW - Rats KW - Exudates and Transudates -- cytology KW - Leukocyte Count -- drug effects KW - Animals KW - Rats, Sprague-Dawley KW - Edema -- prevention & control KW - Carrageenan -- toxicity KW - Hydralazine -- toxicity KW - Foot KW - Blood Pressure -- drug effects KW - Male KW - Exudates and Transudates -- chemistry KW - Hypotension -- chemically induced KW - Inflammation -- physiopathology KW - Receptors, Corticotropin-Releasing Hormone -- physiology KW - Hypotension -- complications KW - Corticotropin-Releasing Hormone -- physiology KW - Corticotropin-Releasing Hormone -- toxicity KW - Receptors, Corticotropin-Releasing Hormone -- drug effects KW - Inflammation -- drug therapy KW - Anti-Inflammatory Agents, Non-Steroidal -- toxicity KW - Corticotropin-Releasing Hormone -- pharmacology KW - Inflammation -- complications KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69716246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroimmunomodulation&rft.atitle=Urocortin+and+inflammation%3A+confounding+effects+of+hypotension+on+measures+of+inflammation.&rft.au=Torpy%2C+D+J%3BWebster%2C+E+L%3BZachman%2C+E+K%3BAguilera%2C+G%3BChrousos%2C+G+P&rft.aulast=Torpy&rft.aufirst=D&rft.date=1999-05-01&rft.volume=6&rft.issue=3&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=Neuroimmunomodulation&rft.issn=10217401&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of cytochrome P-450 2E1 in methacrylonitrile metabolism and disposition. AN - 69715547; 10215687 AB - Methacrylonitrile (MAN) is a widely used aliphatic nitrile and is structurally similar to the known rat carcinogen and suspected human carcinogen acrylonitrile (AN). There is evidence that AN is metabolized via the cytochrome P-450 (CYP) 2E1. Recently, we identified two biliary conjugates originating from the interaction of MAN and its epoxide with glutathione. Mercapturic acids formed via the degradation of the two conjugates were also identified in rat and mouse urine. Additionally, a significant portion of MAN was eliminated in the expired air as CO2 (formed via the epoxide pathway) and unchanged MAN. The objective of the present work was to determine whether CYP2E1 is involved in the oxidative metabolism of MAN as was suggested for AN. 2-14C-MAN was administered to CYP2E1-null or wild-type mice by gavage at 12 mg/kg. Although total urinary and fecal excretion of MAN-derived radioactivity was slightly different in CYP2E1-null versus wild-type mice, the ratio of mercapturic acids originating from the epoxide-glutathione versus MAN-glutathione conjugates were lower in urine of CYP2E1-null mice than in that of wild-type animals. Exhalation of MAN-derived organic volatiles (primarily parent MAN) was 12- and 42-fold greater in female and male CYP2E1-null mice than in wild-type mice, respectively. Additionally, exhalation of CO2 derived from metabolism of MAN via the CYP2E1 pathway was 3- to 5-fold greater in wild-type than in CYP2E1-null animals. Although these data indicate that CYP2E1 is the principal enzyme responsible for the oxidative metabolism of MAN, other cytochrome P-450 enzymes may be involved. Assessment of MAN metabolism in CYP2E1-null mice pretreated with 1-aminobenzotriazole (CYP inhibitor) resulted in a further decrease in oxidative metabolites of MAN. Comparison of the tissue concentrations of MAN-derived radioactivity in mouse tissues revealed that MAN-derived radioactivity is generally higher in wild-type > CYP2E1-null mice > CYP2E1-null mice pretreated with 1-aminobenzotriazole, suggesting a direct relationship between MAN oxidative metabolism and the half-life of MAN and/or its metabolites in various tissues. It is therefore concluded that MAN oxidative metabolites such as the epoxide intermediate have greater reactivity than parent MAN. JF - The Journal of pharmacology and experimental therapeutics AU - Ghanayem, B I AU - Sanders, J M AU - Chanas, B AU - Burka, L T AU - Gonzalez, F J AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. Ghanayem@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 1054 EP - 1059 VL - 289 IS - 2 SN - 0022-3565, 0022-3565 KW - Methacrylates KW - 0 KW - Nitriles KW - methacrylonitrile KW - 04S4K38612 KW - N-acetyl-S-(2-carboxypropyl)cysteine KW - 73614-35-4 KW - Cytochrome P-450 CYP2E1 KW - EC 1.14.13.- KW - Acetylcysteine KW - WYQ7N0BPYC KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Acetylcysteine -- urine KW - Acetylcysteine -- analogs & derivatives KW - Biotransformation KW - Mice KW - Tissue Distribution KW - Feces -- chemistry KW - Male KW - Female KW - Chromatography, High Pressure Liquid KW - Mice, Knockout KW - Nitriles -- pharmacokinetics KW - Methacrylates -- pharmacokinetics KW - Methacrylates -- toxicity KW - Nitriles -- metabolism KW - Methacrylates -- metabolism KW - Cytochrome P-450 CYP2E1 -- metabolism KW - Nitriles -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69715547?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Role+of+cytochrome+P-450+2E1+in+methacrylonitrile+metabolism+and+disposition.&rft.au=Ghanayem%2C+B+I%3BSanders%2C+J+M%3BChanas%2C+B%3BBurka%2C+L+T%3BGonzalez%2C+F+J&rft.aulast=Ghanayem&rft.aufirst=B&rft.date=1999-05-01&rft.volume=289&rft.issue=2&rft.spage=1054&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. AN - 69714370; 10216096 AB - CD40 is present on B cells, monocytes, dendritic cells, and endothelial cells, as well as a variety of neoplastic cell types, including carcinomas. CD40 stimulation by an antibody has previously been demonstrated to induce activation-induced cell death in aggressive histology human B-cell lymphoma cell lines. Therefore, we wanted to assess the effects of a recombinant soluble human CD40 ligand (srhCD40L) on human breast carcinoma cell lines. Human breast carcinoma cell lines were examined for CD40 expression by flow cytometry. CD40 expression could be detected on several human breast cancer cell lines and this could be augmented with interferon-gamma. The cell lines were then incubated with a srhCD40L to assess effects on in vitro growth. srhCD40L significantly inhibited the proliferation of the CD40(+) human breast cancer cell lines. This inhibition could also be augmented with interferon-gamma. Viability was also affected and this was shown to be due to increased apoptosis of the cell lines in response to the ligand. Treatment of tumor-bearing mice was then performed to assess the in vivo efficacy of the ligand. Treatment of tumor-bearing SCID mice with the ligand resulted in significant increases in survival. Thus, CD40 stimulation by its ligand directly inhibits human breast carcinoma cells in vitro and in vivo. These results suggest that srhCD40L may be of clinical use to inhibit human breast carcinoma growth. JF - Blood AU - Hirano, A AU - Longo, D L AU - Taub, D D AU - Ferris, D K AU - Young, L S AU - Eliopoulos, A G AU - Agathanggelou, A AU - Cullen, N AU - Macartney, J AU - Fanslow, W C AU - Murphy, W J AD - Laboratory of Leukocyte Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD, USA. Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 2999 EP - 3007 VL - 93 IS - 9 SN - 0006-4971, 0006-4971 KW - Antigens, CD KW - 0 KW - Antigens, CD40 KW - Ligands KW - Membrane Glycoproteins KW - Recombinant Proteins KW - CD40 Ligand KW - 147205-72-9 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Antigens, CD -- physiology KW - Apoptosis KW - Carcinoma, Ductal, Breast -- pathology KW - Humans KW - Antigens, CD -- genetics KW - Mice KW - Cell Survival KW - Recombinant Proteins -- toxicity KW - Tumor Cells, Cultured KW - Transplantation, Heterologous KW - Flow Cytometry KW - Mice, SCID KW - Recombinant Proteins -- therapeutic use KW - Female KW - Cell Division KW - Breast Neoplasms -- immunology KW - Antigens, CD40 -- physiology KW - Membrane Glycoproteins -- toxicity KW - Breast Neoplasms -- pathology KW - Membrane Glycoproteins -- therapeutic use KW - Antigens, CD40 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69714370?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Inhibition+of+human+breast+carcinoma+growth+by+a+soluble+recombinant+human+CD40+ligand.&rft.au=Hirano%2C+A%3BLongo%2C+D+L%3BTaub%2C+D+D%3BFerris%2C+D+K%3BYoung%2C+L+S%3BEliopoulos%2C+A+G%3BAgathanggelou%2C+A%3BCullen%2C+N%3BMacartney%2C+J%3BFanslow%2C+W+C%3BMurphy%2C+W+J&rft.aulast=Hirano&rft.aufirst=A&rft.date=1999-05-01&rft.volume=93&rft.issue=9&rft.spage=2999&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-18 N1 - Date created - 1999-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine. AN - 69710625; 10215643 AB - Convulsions associated with cocaine abuse can be life threatening and resistant to standard emergency treatment. Cocaine (75 mg/kg, i. p.) produced clonic convulsions in approximately 90% of male, Swiss-Webster mice. A variety of clinically used antiepileptic agents did not significantly protect against cocaine convulsions (e. g., diazepam and phenobarbital). Anticonvulsants in clinical practice that did significantly protect against convulsion did so only at doses with significant sedative/ataxic effects (e.g., clonazepam and valproic acid). In contrast, functional N-methyl-D-aspartate (NMDA) antagonists all produced dose-dependent and significant protection against the convulsant effects of cocaine. Anticonvulsant efficacy was achieved by blockade of both competitive and noncompetitive modulatory sites on the NMDA receptor complex. Thus, competitive antagonists, ion-channel blockers, polyamine antagonists, and functional blockers of the strychnine-insensitive glycine modulatory site all prevented cocaine seizures. The role of NMDA receptors in the control of cocaine-induced convulsions was further strengthened by the positive correlation between the potencies of noncompetititve antagonists or competitive antagonists to block convulsions and their respective affinities for their specific binding sites on the NMDA receptor complex. Although some NMDA blockers produced profound behavioral side effects at efficacious doses (e.g., noncompetitive antagonists), others (e.g., some low-affinity channel blockers, some competitive antagonists, and glycine antagonists) demonstrated significant and favorable separation between their anticonvulsant and side effect profiles. The present results provide the most extensive evidence to date identifying NMDA receptor blockade as a potential strategy for the discovery of agents for clinical use in averting toxic sequelae from cocaine overdose. Given the literature suggesting a role for these drugs in other areas of drug abuse treatments, NMDA receptor antagonists sit in a unique position as potential therapeutic candidates. JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Gasior, M AU - Heifets, B AU - Tortella, F C AD - Drug Development Group, Behavioral Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA. jwitkin@intra.nida.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 703 EP - 711 VL - 289 IS - 2 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Excitatory Amino Acid Antagonists KW - Receptors, Glycine KW - N-Methylaspartate KW - 6384-92-5 KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Behavior, Animal -- drug effects KW - Animals KW - Ataxia -- chemically induced KW - Dose-Response Relationship, Drug KW - Mice KW - Receptors, Glycine -- antagonists & inhibitors KW - Male KW - Binding Sites KW - Seizures -- chemically induced KW - Anticonvulsants -- pharmacology KW - Excitatory Amino Acid Antagonists -- toxicity KW - N-Methylaspartate -- antagonists & inhibitors KW - Anticonvulsants -- toxicity KW - Seizures -- prevention & control KW - Excitatory Amino Acid Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69710625?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Anticonvulsant+efficacy+of+N-methyl-D-aspartate+antagonists+against+convulsions+induced+by+cocaine.&rft.au=Witkin%2C+J+M%3BGasior%2C+M%3BHeifets%2C+B%3BTortella%2C+F+C&rft.aulast=Witkin&rft.aufirst=J&rft.date=1999-05-01&rft.volume=289&rft.issue=2&rft.spage=703&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quinolinic acid is extruded from the brain by a probenecid-sensitive carrier system: a quantitative analysis. AN - 69709096; 10217295 AB - Although the neurotoxic tryptophan-kynurenine pathway metabolite quinolinic acid originates in brain by both local de novo synthesis and entry from blood, its concentrations in brain parenchyma, extracellular fluid, and CSF are normally below blood values. In the present study, an intraperitoneal injection of probenecid (400 mg/kg), an established inhibitor of acid metabolite transport in brain, into gerbils, increased quinolinic acid concentrations in striatal homogenates, CSF, serum, and homogenates of kidney and liver. Direct administration of probenecid (10 mM) into the brain compartment via an in vivo microdialysis probe implanted into the striatum also caused a progressive elevation in both quinolinic acid and homovanillic acid concentrations in the extracellular fluid compartment but was without effect on serum quinolinic acid levels. A model of microdialysis transport showed that the elevations in extracellular fluid quinolinic acid and homovanillic acid levels following intrastriatal application are consistent with probenecid block of a microvascular acid transport mechanism. We conclude that quinolinic acid in brain is maintained at concentrations below blood levels largely by active extrusion via a probenecid-sensitive carrier system. JF - Journal of neurochemistry AU - Morrison, P F AU - Morishige, G M AU - Beagles, K E AU - Heyes, M P AD - Bioengineering and Physical Science Program, Office of Research Services, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1262, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2135 EP - 2144 VL - 72 IS - 5 SN - 0022-3042, 0022-3042 KW - Carrier Proteins KW - 0 KW - Quinolinic Acid KW - F6F0HK1URN KW - Probenecid KW - PO572Z7917 KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Osmolar Concentration KW - Gerbillinae KW - Animals KW - Computer Simulation KW - Extracellular Space -- metabolism KW - Corpus Striatum -- metabolism KW - Homovanillic Acid -- metabolism KW - Models, Biological KW - Female KW - Carrier Proteins -- metabolism KW - Quinolinic Acid -- metabolism KW - Quinolinic Acid -- blood KW - Probenecid -- pharmacology KW - Brain -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69709096?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Quinolinic+acid+is+extruded+from+the+brain+by+a+probenecid-sensitive+carrier+system%3A+a+quantitative+analysis.&rft.au=Morrison%2C+P+F%3BMorishige%2C+G+M%3BBeagles%2C+K+E%3BHeyes%2C+M+P&rft.aulast=Morrison&rft.aufirst=P&rft.date=1999-05-01&rft.volume=72&rft.issue=5&rft.spage=2135&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes. AN - 69698210; 10207070 AB - Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal binding proteins that unfold the higher-order chromatin structure, thereby enhancing the transcription and replication potential of chromatin. Here we report that PCAF, a transcription coactivator with intrinsic histone acetyltransferase activity, specifically acetylates HMG-17 but not HMG-14. Using mass spectrum sequence analysis, we identified the lysine at position 2 as the predominant site acetylated by PCAF. Lysine 2 is a prominent acetylation site in vivo, suggesting that this PCAF-mediated acetylation is physiologically relevant. Experiments with HMG-17 deletion mutants and competition studies with various protein fragments indicate that the specific acetylation of HMG-17 is not determined solely by the primary sequence near the acetylation site. By equilibrium dialysis we demonstrated that acetylation reduces the affinity of HMG-17 to nucleosome cores. In addition, we found that the binding of HMG-14 and HMG-17 to nucleosome cores inhibits the PCAF-mediated acetylation of histone H3. Thus, the presence of HMG-14 and HMG-17 affects the ability of PCAF to acetylate chromatin, while the acetylation of HMG-17 reduces its binding affinity to chromatin. Conceivably, in HMG-17-containing chromatin, acetylation of HMG-17 precedes the acetylation of histones. JF - Molecular and cellular biology AU - Herrera, J E AU - Sakaguchi, K AU - Bergel, M AU - Trieschmann, L AU - Nakatani, Y AU - Bustin, M AD - Protein Section, Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Herr@helix.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 3466 EP - 3473 VL - 19 IS - 5 SN - 0270-7306, 0270-7306 KW - Chromatin KW - 0 KW - High Mobility Group Proteins KW - Histones KW - Nucleosomes KW - Peptide Fragments KW - Recombinant Proteins KW - Saccharomyces cerevisiae Proteins KW - Transcription Factors KW - Acetyltransferases KW - EC 2.3.1.- KW - Histone Acetyltransferases KW - EC 2.3.1.48 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mass Spectrometry KW - Animals KW - Acetylation KW - Cattle KW - Chromatin -- metabolism KW - Transcription Factors -- metabolism KW - Recombinant Proteins -- metabolism KW - Humans KW - Histones -- metabolism KW - Peptide Fragments -- pharmacology KW - Lysine -- metabolism KW - High Mobility Group Proteins -- chemistry KW - Acetyltransferases -- metabolism KW - Nucleosomes -- metabolism KW - High Mobility Group Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69698210?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Specific+acetylation+of+chromosomal+protein+HMG-17+by+PCAF+alters+its+interaction+with+nucleosomes.&rft.au=Herrera%2C+J+E%3BSakaguchi%2C+K%3BBergel%2C+M%3BTrieschmann%2C+L%3BNakatani%2C+Y%3BBustin%2C+M&rft.aulast=Herrera&rft.aufirst=J&rft.date=1999-05-01&rft.volume=19&rft.issue=5&rft.spage=3466&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-18 N1 - Date created - 1999-05-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1972 Apr 10;247(7):2026-33 [5016641] Nucleic Acids Res. 1980 Sep 11;8(17):3757-78 [6449690] J Mol Biol. 1989 Apr 5;206(3):451-63 [2716057] Biochim Biophys Acta. 1990 Jul 30;1049(3):231-43 [2200521] Trends Biochem Sci. 1992 May;17(5):187-91 [1595128] J Mol Biol. 1992 Nov 20;228(2):442-9 [1453455] EMBO J. 1993 Oct;12(10):3855-64 [8404854] J Mol Biol. 1994 Feb 11;236(1):189-98 [8107104] Science. 1994 Aug 5;265(5173):796-9 [8047885] Nucleic Acids Res. 1994 Oct 25;22(21):4520-6 [7971283] Annu Rev Biochem. 1994;63:265-97 [7979240] EMBO J. 1995 Apr 3;14(7):1478-89 [7729423] Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6364-8 [7603997] Mol Cell Biol. 1997 Oct;17(10):5843-55 [9315642] J Biol Chem. 1997 Oct 24;272(43):27253-8 [9341171] J Mol Biol. 1997 Dec 12;274(4):454-65 [9417927] Nature. 1998 Feb 5;391(6667):601-5 [9468140] Cell Mol Life Sci. 1998 Jan;54(1):6-20 [9487383] Genes Dev. 1998 Mar 1;12(5):599-606 [9499396] J Biol Chem. 1998 Apr 17;273(16):9409-14 [9545265] Nature. 1998 Apr 23;392(6678):831-5 [9572144] Proc Natl Acad Sci U S A. 1998 May 12;95(10):5468-73 [9576905] Curr Opin Genet Dev. 1998 Apr;8(2):165-72 [9610406] Curr Opin Genet Dev. 1998 Apr;8(2):173-8 [9610407] Proc Natl Acad Sci U S A. 1964 May;51:786-94 [14172992] J Biol Chem. 1995 Jul 28;270(30):17923-8 [7629098] Genes Dev. 1995 Aug 15;9(16):1978-91 [7649479] EMBO J. 1995 Aug 15;14(16):3946-57 [7664735] J Mol Biol. 1995 Sep 29;252(4):423-32 [7563062] Mol Cell Biol. 1995 Dec;15(12):6663-9 [8524231] Semin Cell Biol. 1995 Aug;6(4):229-36 [8562915] J Biol Chem. 1996 May 17;271(20):12009-16 [8662614] EMBO J. 1996 May 15;15(10):2508-18 [8665858] Curr Opin Genet Dev. 1996 Apr;6(2):176-84 [8722174] Prog Nucleic Acid Res Mol Biol. 1996;54:35-100 [8768072] Nature. 1996 Jul 25;382(6589):319-24 [8684459] Mol Cell Biol. 1996 Aug;16(8):4349-56 [8754835] Nature. 1996 Sep 19;383(6597):269-72 [8805705] Crit Rev Eukaryot Gene Expr. 1996;6(2-3):149-88 [8855387] Cell. 1996 Oct 4;87(1):5-8 [8858142] Cell. 1996 Nov 29;87(5):953-9 [8945521] Cell. 1996 Dec 27;87(7):1261-70 [8980232] Trends Biochem Sci. 1997 Apr;22(4):128-32 [9149532] Genes Dev. 1997 Jul 1;11(13):1640-50 [9224714] Curr Biol. 1997 Sep 1;7(9):689-92 [9285713] Nature. 1997 Sep 18;389(6648):251-60 [9305837] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Nat New Biol. 1973 Oct 17;245(146):207-9 [4126973] J Biol Chem. 1979 Apr 25;254(8):2918-22 [85628] J Biol Chem. 1979 Nov 25;254(22):11577-83 [500660] Science. 1980 Sep 26;209(4464):1534-6 [7433974] J Biol Chem. 1981 Sep 10;256(17):8892-5 [6455433] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of actin cytoskeleton in lymphocytes: PKC-delta disrupts IL-3-induced membrane ruffles downstream of Rac1. AN - 69682819; 10199555 AB - In the murine pre-B lymphoid cell line Baf3, the presence of IL-3 is required for the formation of membrane ruffles that intensely stain for actin and are responsible for the elongated cell phenotype. Withdrawal of IL-3 dissolves ruffled protrusions and converts the cell phenotype to round. Flow cytometric analysis of the cell shape showed that an inactive analog of Rac1 but not inactive RhoA or inactive cdc42 rounds the cells in the presence of IL-3. Constitutively activated Rac1 restores the elongated cell phenotype to IL-3-starved cells. We conclude that the activity of Rac1 is necessary and sufficient for the IL-3-induced assembly of membrane ruffles. Similar to the IL-3 withdrawal, phorbol 12-myristate 13-acetate (PMA) dissolves actin-formed membrane ruffles and rounds the cells in the presence of IL-3. Flow cytometric analysis of the cell shape demonstrated that in the presence of IL-3 the PMA-induced cell rounding cannot be abolished by constitutively active Rac1 but can be imitated by inactive Rac1. These data indicate that PMA disrupts the IL-3 pathway downstream of Rac1. Cells rounded by PMA return to the elongated phenotype concomitantly with PKC depletion. PMA-induced cell rounding can be reversed by the PKC-specific inhibitor GF109203X. Experiments with overexpression in Baf3 of individual PKC isoforms and a dominant negative PKC-delta indicate that activation of PKC-delta but not other PKC isoforms is responsible for disruption of membrane ruffles. JF - Journal of cellular physiology AU - Romanova, L Y AU - Alexandrov, I A AU - Blagosklonny, M V AU - Nordan, R P AU - Garfield, S AU - Acs, P AU - Nguyen, P AU - Trepel, J AU - Blumberg, P M AU - Mushinski, J F AD - Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. romanovl@dc37a.nci.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 157 EP - 169 VL - 179 IS - 2 SN - 0021-9541, 0021-9541 KW - Actins KW - 0 KW - Indoles KW - Interleukin-3 KW - Isoenzymes KW - Maleimides KW - Tubulin KW - Cytochalasin D KW - 22144-77-0 KW - Prkcd protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-delta KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - rac GTP-Binding Proteins KW - EC 3.6.5.2 KW - bisindolylmaleimide I KW - L79H6N0V6C KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cytoskeleton -- metabolism KW - Cell Membrane -- drug effects KW - Tubulin -- metabolism KW - Mice KW - Cell Size -- drug effects KW - Phenotype KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cytochalasin D -- pharmacology KW - Indoles -- pharmacology KW - Cell Line KW - Maleimides -- pharmacology KW - Isoenzymes -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Interleukin-3 -- pharmacology KW - GTP-Binding Proteins -- metabolism KW - Actins -- metabolism KW - B-Lymphocytes -- metabolism KW - Protein Kinase C -- pharmacology KW - Isoenzymes -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69682819?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cellular+physiology&rft.atitle=Regulation+of+actin+cytoskeleton+in+lymphocytes%3A+PKC-delta+disrupts+IL-3-induced+membrane+ruffles+downstream+of+Rac1.&rft.au=Romanova%2C+L+Y%3BAlexandrov%2C+I+A%3BBlagosklonny%2C+M+V%3BNordan%2C+R+P%3BGarfield%2C+S%3BAcs%2C+P%3BNguyen%2C+P%3BTrepel%2C+J%3BBlumberg%2C+P+M%3BMushinski%2C+J+F&rft.aulast=Romanova&rft.aufirst=L&rft.date=1999-05-01&rft.volume=179&rft.issue=2&rft.spage=157&rft.isbn=&rft.btitle=&rft.title=Journal+of+cellular+physiology&rft.issn=00219541&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-27 N1 - Date created - 1999-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of human immunodeficiency virus type 1 Gag to membrane: role of the matrix amino terminus. AN - 69682296; 10196310 AB - Binding of the human immunodeficiency virus type 1 (HIV-1) Gag protein precursor, Pr55(Gag), to membrane is an indispensable step in virus assembly. Previously, we reported that a matrix (MA) residue 6 substitution (6VR) imposed a virus assembly defect similar to that observed with myristylation-defective mutants, suggesting that the 6VR change impaired membrane binding. Intriguingly, the 6VR mutation had no effect on Gag myristylation. The defective phenotype imposed by 6VR was reversed by changes at other positions in MA, including residue 97. In this study, we use several biochemical methods to demonstrate that the residue 6 mutation, as well as additional substitutions in MA amino acids 7 and 8, reduce membrane binding without affecting N-terminal myristylation. This effect is observed in the context of Pr55(Gag), a truncated Gag containing only MA and CA, and in MA itself. The membrane binding defect imposed by the 6VR mutation is reversed by second-site changes in MA residues 20 and 97, both of which, when present alone, increase membrane binding to levels greater than those for the wild type. Both reduced and enhanced membrane binding imposed by the MA substitutions depend upon the presence of the N-terminal myristate. The results support the myristyl switch model recently proposed for the regulation of Gag membrane binding, according to which membrane binding is determined by the degree of exposure or sequestration of the N-terminal myristate moiety. Alternatively, insertion of the myristate into the lipid bilayer might be a prerequisite event for the function of other distinct MA-encoded membrane binding domains. JF - Journal of virology AU - Ono, A AU - Freed, E O AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 4136 EP - 4144 VL - 73 IS - 5 SN - 0022-538X, 0022-538X KW - Capsid Proteins KW - 0 KW - Gene Products, gag KW - HIV Antigens KW - NCP7 protein, Human immunodeficiency virus 1 KW - Protein Precursors KW - Viral Proteins KW - gag Gene Products, Human Immunodeficiency Virus KW - p17 protein, Human Immunodeficiency Virus Type 1 KW - p55 gag precursor protein, Human immunodeficiency virus 1 KW - Myristic Acid KW - 0I3V7S25AW KW - Index Medicus KW - AIDS/HIV KW - Virus Assembly KW - HeLa Cells KW - Humans KW - Molecular Sequence Data KW - Capsid -- metabolism KW - Amino Acid Sequence KW - Cell Membrane -- metabolism KW - Myristic Acid -- metabolism KW - Mutagenesis KW - HIV Antigens -- physiology KW - Gene Products, gag -- genetics KW - HIV-1 -- genetics KW - Gene Products, gag -- physiology KW - Protein Precursors -- metabolism KW - Protein Precursors -- genetics KW - HIV-1 -- physiology KW - Gene Products, gag -- metabolism KW - HIV-1 -- metabolism KW - HIV Antigens -- metabolism KW - HIV Antigens -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69682296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Binding+of+human+immunodeficiency+virus+type+1+Gag+to+membrane%3A+role+of+the+matrix+amino+terminus.&rft.au=Ono%2C+A%3BFreed%2C+E+O&rft.aulast=Ono&rft.aufirst=A&rft.date=1999-05-01&rft.volume=73&rft.issue=5&rft.spage=4136&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-19 N1 - Date created - 1999-05-19 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Virol. 1995 Nov;69(11):6810-8 [7474093] Trends Biochem Sci. 1995 Jul;20(7):272-6 [7667880] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3099-104 [8610175] J Virol. 1996 Dec;70(12):8540-8 [8970978] J Virol. 1997 Jun;71(6):4409-18 [9151831] J Virol. 1997 Sep;71(9):6582-92 [9261380] Nature. 1997 Sep 11;389(6647):198-202 [9296500] Virology. 1998 Jan 5;240(1):27-35 [9448686] J Virol. 1998 Apr;72(4):2723-32 [9525590] Virology. 1998 Mar 30;243(1):78-93 [9527917] J Virol. 1998 May;72(5):4116-26 [9557701] EMBO J. 1998 May 1;17(9):2699-708 [9564051] Virology. 1998 Jul 5;246(2):191-8 [9657938] J Virol. 1998 Sep;72(9):7659-63 [9696871] J Virol. 1998 Nov;72(11):9061-8 [9765451] Virology. 1998 Nov 10;251(1):1-15 [9813197] J Virol. 1986 Aug;59(2):284-91 [3016298] Proc Natl Acad Sci U S A. 1986 Oct;83(19):7246-50 [3489936] J Virol. 1988 Feb;62(2):479-87 [2826810] J Virol. 1988 Sep;62(9):3217-23 [2841473] Annu Rev Biochem. 1988;57:69-99 [3052287] J Cell Biol. 1988 Nov;107(5):1707-15 [2846585] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580-4 [2849111] J Virol. 1989 May;63(5):2370-3 [2649693] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5 [2788277] Proc Natl Acad Sci U S A. 1990 Jan;87(2):523-7 [2405382] AIDS Res Hum Retroviruses. 1990 Jun;6(6):721-30 [2194551] J Virol. 1990 Aug;64(8):3995-4001 [2164607] AIDS. 1991 Jun;5(6):639-54 [1883539] J Biol Chem. 1991 Oct 15;266(29):19599-610 [1918067] J Virol. 1992 Aug;66(8):4966-71 [1629961] J Virol. 1993 Jan;67(1):407-14 [8380086] J Virol. 1993 Aug;67(8):4972-80 [8331736] Biochemistry. 1993 Oct 5;32(39):10436-43 [8399188] J Virol. 1993 Nov;67(11):6387-94 [8411340] J Virol. 1993 Dec;67(12):7067-76 [7693966] J Virol. 1994 Jan;68(1):441-7 [8254754] J Virol. 1994 Mar;68(3):1689-96 [8107229] J Virol. 1994 Apr;68(4):2503-12 [8139032] J Virol. 1994 Apr;68(4):2556-69 [8139035] J Virol. 1994 May;68(5):3232-42 [8151785] Proc Natl Acad Sci U S A. 1994 May 10;91(10):4594-8 [8183954] J Virol. 1994 Aug;68(8):5311-20 [8035531] J Virol. 1994 Oct;68(10):6644-54 [7521919] J Mol Biol. 1994 Nov 25;244(2):198-223 [7966331] Virology. 1994 Nov 15;205(1):336-44 [7975229] Biochem Biophys Res Commun. 1994 Nov 15;204(3):1031-8 [7980574] J Virol. 1995 Mar;69(3):1984-9 [7853546] J Virol. 1995 Jun;69(6):3949-54 [7745752] J Virol. 1995 Sep;69(9):5455-60 [7636991] J Virol. 1996 Jan;70(1):341-51 [8523546] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation of a new clinical lot of Escherichia coli O:113 endotoxin. AN - 69681440; 10191237 AB - The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to humans has been an important means to study inflammation in vivo; however, the supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center reference endotoxin [CCRE]), derived from the original bulk material extracted from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in dose-related increases in symptoms, temperature (P=. 016), total leukocyte count (P=.014), tumor necrosis factor-alpha (P=.004), interleukin (IL)-1 receptor antagonist (P=.004), IL-6 (P=. 005), IL-8 (P=.011), cortisol (P<.05), and C-reactive protein (P=. 04). These responses were attenuated (all P<.012) in subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy subjects, the magnitude of exposure to CCRE results in a graded dose response of major components of innate immunity. JF - The Journal of infectious diseases AU - Suffredini, A F AU - Hochstein, H D AU - McMahon, F G AD - Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. anthony_suffredini@nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 1278 EP - 1282 VL - 179 IS - 5 SN - 0022-1899, 0022-1899 KW - Cytokines KW - 0 KW - Endotoxins KW - endotoxin, Escherichia coli KW - 67924-63-4 KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - United States KW - Cytokines -- blood KW - Injections, Intravenous KW - Dose-Response Relationship, Drug KW - Humans KW - Reference Standards KW - Hydrocortisone -- blood KW - Leukocyte Count KW - Evaluation Studies as Topic KW - Adult KW - National Institutes of Health (U.S.) KW - Middle Aged KW - Male KW - Endotoxins -- administration & dosage KW - Inflammation -- immunology KW - Endotoxins -- toxicity KW - Inflammation -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69681440?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Dose-related+inflammatory+effects+of+intravenous+endotoxin+in+humans%3A+evaluation+of+a+new+clinical+lot+of+Escherichia+coli+O%3A113+endotoxin.&rft.au=Suffredini%2C+A+F%3BHochstein%2C+H+D%3BMcMahon%2C+F+G&rft.aulast=Suffredini&rft.aufirst=A&rft.date=1999-05-01&rft.volume=179&rft.issue=5&rft.spage=1278&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Human immunodeficiency virus type 1 infection, mucosal immunity, and pathogenesis and extramural research programs at the National Institutes of Health. AN - 69662964; 10099104 JF - The Journal of infectious diseases AU - Kresina, T F AU - Mathieson, B AD - Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-6600, USA. tk13v@nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - S392 EP - S396 VL - 179 Suppl 3 SN - 0022-1899, 0022-1899 KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - United States KW - Homosexuality, Male KW - Sex Factors KW - Humans KW - National Institutes of Health (U.S.) KW - Heterosexuality KW - Male KW - Female KW - Substance Abuse, Intravenous KW - HIV Infections -- transmission KW - HIV-1 -- pathogenicity KW - HIV Infections -- immunology KW - Immunity, Mucosal UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69662964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Human+immunodeficiency+virus+type+1+infection%2C+mucosal+immunity%2C+and+pathogenesis+and+extramural+research+programs+at+the+National+Institutes+of+Health.&rft.au=Kresina%2C+T+F%3BMathieson%2C+B&rft.aulast=Kresina&rft.aufirst=T&rft.date=1999-05-01&rft.volume=179+Suppl+3&rft.issue=&rft.spage=S392&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Optimizing radiation therapy of brain tumours by combination of 5-bromo-2-deoxy-uridine & 2-deoxy-D-glucose. AN - 69407189; 10643143 AB - The effects of 5-bromo-2-deoxy-uridine (BrdU) and 2-deoxy-D-glucose (2-DG) on 60Co-gamma ray induced damage were studied in a human glioma cell line grown as monolayer. Radiation induced micronuclei formation was used as an index of cytogenetic damage. Exponentially growing cells (doubling time 16-20 h) were incubated in the presence of BrdU (0.8 microM, in dark) for 24 h. After removing BrdU, cells were irradiated (1-4 Gy), incubated with or without 2-DG (2-3 h), and grown further (for 18, 24, 30 or 45 h) for assay of damage. It was observed that (i) BrdU and 2-DG treatments did not induce micronuclei formation in unirradiated cultures; (ii) pre-irradiation presence of BrdU increased the gamma-ray induced micronuclei formation; (iii) incubation of irradiated cells under sub-optimal growth conditions [Dulbecco's modified minimal essential medium (DMEM) + 1% serum, or DMEM alone] instead of growth medium (DMEM + 5% serum) progressively decreased micronuclei formation; and (iv) post-irradiation presence of 2-DG (1.25, 2.5, 5 mM, 2-3 h in DMEM + 1% serum) enhanced the radiation damage with and without BrdU treatment at all the time points studied. These observations suggest that (i) radiation induced lesions leading to micronuclei formation in proliferating cells are, at least, partly repairable; (ii) the presence of 2-DG (2DG/glucose > or = 0.25) for short intervals (approximately 2 h), could enhance radiation damage in proliferating brain tumour cells, in the absence as well as presence of BrdU incorporation; and (iii) the combination of 2-DG could reduce BrdU doses required for radiosensitization of brain tumours, reducing, thereby, its toxic side effects. JF - The Indian journal of medical research AU - Kalia, V K AD - Department of Biophysics, National Institute of Mental Health & Neuro Sciences, Bangalore. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 182 EP - 187 VL - 109 SN - 0971-5916, 0971-5916 KW - Radiation-Sensitizing Agents KW - 0 KW - Deoxyglucose KW - 9G2MP84A8W KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Micronucleus Tests KW - Tumor Cells, Cultured KW - DNA Damage KW - Humans KW - Radiotherapy -- methods KW - Radiation-Sensitizing Agents -- therapeutic use KW - Deoxyglucose -- therapeutic use KW - Brain Neoplasms -- genetics KW - Radiation Injuries -- prevention & control KW - Brain Neoplasms -- radiotherapy KW - Bromodeoxyuridine -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69407189?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Indian+journal+of+medical+research&rft.atitle=Optimizing+radiation+therapy+of+brain+tumours+by+combination+of+5-bromo-2-deoxy-uridine+%26amp%3B+2-deoxy-D-glucose.&rft.au=Kalia%2C+V+K&rft.aulast=Kalia&rft.aufirst=V&rft.date=1999-05-01&rft.volume=109&rft.issue=&rft.spage=182&rft.isbn=&rft.btitle=&rft.title=The+Indian+journal+of+medical+research&rft.issn=09715916&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-02-11 N1 - Date created - 2000-02-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cisplatin, radiation, and amifostine in carcinoma of the uterine cervix. AN - 1859346757; 11240771 AB - A pilot, open, comparative study was performed on patients with locally advanced cervical cancer to investigate the efficacy and safety of amifostine. Twenty patients with a histologic diagnosis of squamous cervical cancer were treated with radiotherapy and randomized in two groups. Group A received cisplatin at 20 mg/m2 for five days in two cycles during intracavitary radiotherapy and 100 mg/m2 x 2 cycles during external radiotherapy, and amifostine 825 mg/m2 15 min before the cisplatin infusion. Patients in group B received cisplatin in the same doses without amifostine. All patients had complete responses during a median follow-up of 20 months. Grade three neutropenia was present in two patients in group A and in four of the control group, P = 0.31; grade 2 neurologic toxicity was seen in four patients in group B and in one of the patients in group A, P = 0.15. One patient needed temporary interruption of amifostine due to hypotension. Eight of 10 patients in group A developed hypocalcemia during the treatment with amifostine. Our findings indicate that amifostine was well tolerated. In this series a mild neurologic and hematologic protection was found in patients that received amifostine, although this was not statistically significant. No differences in disease-free survival response and overall survival was seen between the two groups. JF - International journal of gynecological cancer : official journal of the International Gynecological Cancer Society AU - Gallardo, D. AU - Mohar, A. AU - Calderillo, G. AU - Mota, A. AU - Solorza, G. AU - Lozano, A. AU - Solano, P. AU - De La Garza, J. AD - Department of Medical Oncology, National Cancer Institute and Biomedical Investigations Institute, UNAM, Tlalpan, Mexico; Department of Radiotherapy, National Cancer Institute and Biomedical Investigations Institute, UNAM, Tlalpan, Mexico; Department of Gynecology, National Cancer Institute and Biomedical Investigations Institute, UNAM, Tlalpan, Mexico; Division of Clinical Research, National Cancer Institute and Biomedical Investigations Institute, UNAM, Tlalpan, Mexico. Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 225 EP - 230 VL - 9 IS - 3 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859346757?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+gynecological+cancer+%3A+official+journal+of+the+International+Gynecological+Cancer+Society&rft.atitle=Cisplatin%2C+radiation%2C+and+amifostine+in+carcinoma+of+the+uterine+cervix.&rft.au=Gallardo%2C+D.%3BMohar%2C+A.%3BCalderillo%2C+G.%3BMota%2C+A.%3BSolorza%2C+G.%3BLozano%2C+A.%3BSolano%2C+P.%3BDe+La+Garza%2C+J.&rft.aulast=Gallardo&rft.aufirst=D.&rft.date=1999-05-01&rft.volume=9&rft.issue=3&rft.spage=225&rft.isbn=&rft.btitle=&rft.title=International+journal+of+gynecological+cancer+%3A+official+journal+of+the+International+Gynecological+Cancer+Society&rft.issn=1525-1438&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 2001-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Papillomavirus-like particle vaccines for cervical cancer AN - 17401236; 4632935 AB - Most cervical cancers are now known to be caused by human papillomavirus (HPV) infections. This provides an opportunity to prevent a major cause of cancer deaths in women through vaccination. Subunit vaccines based upon non-infectious papillomavirus-like particles (VLPs) are attractive candidates to prevent infection by oncogenic HPVs, and clinical trials are now underway. In addition, the strongly immunogenic characteristics of VLPs raise the possibility that they could also serve as vehicles for inducing therapeutic responses against HPV-induced neoplasia and other diseases. JF - Molecular Medicine Today AU - Schiller, J T AD - Laboratory of Cellular Oncology, National Cancer Institute, Bldg 36, Rm. 1D32, Bethesda, MD 20892, USA, schillej@dc37a.nci.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 209 EP - 215 VL - 5 IS - 5 SN - 1357-4310, 1357-4310 KW - Human papillomavirus KW - cancer vaccines KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Cervical carcinoma KW - Virus-like particles KW - Antitumor agents KW - Neoplasia KW - Reviews KW - Vaccines KW - W3 33350:Cancer vaccines KW - V 22114:Human oncogenic viruses KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17401236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Medicine+Today&rft.atitle=Papillomavirus-like+particle+vaccines+for+cervical+cancer&rft.au=Schiller%2C+J+T&rft.aulast=Schiller&rft.aufirst=J&rft.date=1999-05-01&rft.volume=5&rft.issue=5&rft.spage=209&rft.isbn=&rft.btitle=&rft.title=Molecular+Medicine+Today&rft.issn=13574310&rft_id=info:doi/10.1016%2FS1357-4310%2899%2901463-X LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human papillomavirus; Reviews; Vaccines; Cervical carcinoma; Virus-like particles; Antitumor agents; Neoplasia DO - http://dx.doi.org/10.1016/S1357-4310(99)01463-X ER - TY - JOUR T1 - Anti-Tumor Immunity Elicited by a Recombinant Vaccinia Virus Expressing CD70 (CD27L) AN - 17359744; 4524637 AB - CD70, a ligand of the T cell costimulatory receptor CD27, is expressed mainly on activated B cells and has been shown to increase cytotoxic activity and proliferation of preferentially unprimed T cells. Reported herein is the construction of a recombinant vaccinia virus encoding CD70 (designated rV-CD70) and a demonstration of its biological effect on naive T cells in vitro and in vivo. In a whole tumor cell vaccine model, the growth of CD70-negative murine colon adenocarcinoma (MC38) tumor cells infected with rV-CD70 (multiplicity of infection [MOI] of 0.1) and transplanted into syngeneic C57BL/6 mice was inhibited completely while control tumors infected with wild-type vaccinia grew rapidly and killed mice within 3-5 weeks. Tumor-free mice previously immunized with rV-CD70-infected tumors were partially protected against rechallenge with wild-type tumors, demonstrating the induction of systemic anti-tumor immunity. In addition, immunization of C57BL/6 mice with rV-CD70 admixed with vaccinia virus encoding carcinoembryonic antigen (rV-CEA) was superior to treatment with rV-CEA alone in inducing CEA-specific lymphoproliferative T cell responses and reducing growth of murine colon carcinomas transduced with CEA. These studies demonstrate for the first time the potential utility of a recombinant vaccinia virus expressing CD70 to enhance T cell responses and mediate anti-tumor immunity. JF - Human Gene Therapy AU - Lorenz, MGO AU - Kantor, JA AU - Schlom, J AU - Hodge, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B07, Bethesda, MD 20892-1750, USA Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 1095 EP - 1103 VL - 10 IS - 7 SN - 1043-0342, 1043-0342 KW - C57BL/6 mice KW - CD27L protein KW - CD70 antigen KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Colon KW - Lymphocytes T KW - Vaccines KW - Adenocarcinoma KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17359744?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Anti-Tumor+Immunity+Elicited+by+a+Recombinant+Vaccinia+Virus+Expressing+CD70+%28CD27L%29&rft.au=Lorenz%2C+MGO%3BKantor%2C+JA%3BSchlom%2C+J%3BHodge%2C+J+W&rft.aulast=Lorenz&rft.aufirst=MGO&rft.date=1999-05-01&rft.volume=10&rft.issue=7&rft.spage=1095&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018094 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lymphocytes T; Vaccines; Colon; Adenocarcinoma; Expression vectors; Gene therapy DO - http://dx.doi.org/10.1089/10430349950018094 ER - TY - JOUR T1 - Production of Minigene-Containing Retroviral Vectors Using an Alphavirus/Retrovirus Hybrid Vector System AN - 17359051; 4524646 AB - In an attempt to increase the synthesis of human clotting factors VIII and IX in transduced cells, optimized expression cassettes containing genomic genelike elements (minigenes) were assembled. Plasmid DNA containing factor VIII or factor IX minigenes and driven by three human cellular promoters (albumin, factor IX, PGK) or the strong viral promoter RSV-LTR were electroporated into TE671 and HepG2 cell lines, and clotting factor levels were determined by ELISA. In comparison with a parallel transfection of MLV-LTR-promoted retroviral vector plasmid DNAs, the PGK- and RSV-LTR-promoted minigene constructs produced equal or greater amounts of clotting factor proteins. A factor IX minigene cassette was cloned into the retrovirus-based gene transfer vector LN (in both forward and reverse orientations) and the miningene vector was introduced into the Phoenix retroviral packaging cell line. Analysis of neo super(r) cells demonstrated that insertion of a factor IX minigene into the retroviral vector LN resulted in rearrangement of the factor IX sequence and loss of factor IX expression in the Phoenix packaging cell line. The same factor IX minigene was then inserted into an alphavirus/retrovirus hybrid vector that facilitates the synthesis of retroviral vector RNA in the cytoplasm of cells. Alphavirus/retrovirus virions were produced and used to transduce the Phoenix retroviral vector packaging cell line. The cytoplasmically produced factor IX minigene-containing retroviral vectors were collected and used to transduce TE671 cells. Analysis of transduced cells demonstrated stable transfer of the minigene and expression of factor IX. JF - Human Gene Therapy AU - Wahlfors, J J AU - Morgan, R A AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Bldg. 10, Rm. 10C103, Bethesda, MD 20892-1851, USA, rmorgan@nhgri.nih.gov Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 1197 EP - 1206 VL - 10 IS - 7 SN - 1043-0342, 1043-0342 KW - TE671 cells KW - HepG2 cells KW - Alphavirus KW - Retrovirus KW - coagulation factor IX KW - coagulation factor VIII KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Enzyme-linked immunosorbent assay KW - Gene therapy KW - Plasmids KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17359051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Production+of+Minigene-Containing+Retroviral+Vectors+Using+an+Alphavirus%2FRetrovirus+Hybrid+Vector+System&rft.au=Wahlfors%2C+J+J%3BMorgan%2C+R+A&rft.aulast=Wahlfors&rft.aufirst=J&rft.date=1999-05-01&rft.volume=10&rft.issue=7&rft.spage=1197&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018184 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Expression vectors; Plasmids; Enzyme-linked immunosorbent assay; Gene therapy DO - http://dx.doi.org/10.1089/10430349950018184 ER - TY - JOUR T1 - Dissolved Oxygen Concentration Affects the Accumulation of HIV-1 Recombinant Proteins in Escherichia coli AN - 17312830; 4583455 AB - A central problem in aerobic growth of any culture is the maintenance of dissolved oxygen concentration (DOC) above growth-limiting levels especially in high-cell density fermentations that are usually of the fed-batch type. Fermentor studies have been conducted to determine the influence of DOC on the production of heterologous proteins in Escherichia coli. The results demonstrated that there is a significant degree of product-to-product variation in the response of heterologous protein accumulation to DOC. For translational fusions of the human immunodeficiency virus-1 (HIV-1) proteins p24Gag and Env41, the imposition of a dissolved oxygen (DO) limitation resulted in 100 and 15% increases in the respective product yields. On the other hand, the imposition of a DO limitation had no effect on the production of a similar translational fusion of the HIV-1 protein p55Gag, and a large negative effect on the production of an influenza protein (C13). The stimulatory effects of DOC on p24Gag production were investigated further. The results of my studies suggested that the stimulatory effect observed at reduced agitation rates on p24Gag accumulation was owing to an oxygen effect and not a shear effect. Furthermore, the results of my investigations indicated that the effect a DOC had on the production of p24Gag was strongly influenced by the cell density at which the culture was induced. JF - Applied Biochemistry and Biotechnology AU - Qoronfleh, M W AD - SAIC Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, Structural Biochemistry Program, Frederick, MD 21702-1201, USA, ooronfle@ncifcrf.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 107 EP - 120 VL - 80 IS - 2 SN - 0273-2289, 0273-2289 KW - HIV-1 KW - man KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts; Virology & AIDS Abstracts KW - Translation KW - Aerobic conditions KW - Fermenters KW - Dissolved oxygen KW - Batch culture KW - Fed-batch culture KW - Human immunodeficiency virus 1 KW - Escherichia coli KW - V 22002:AIDS: Molecular and in vitro aspects KW - W2 32580:Fermentation and process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17312830?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+Biochemistry+and+Biotechnology&rft.atitle=Dissolved+Oxygen+Concentration+Affects+the+Accumulation+of+HIV-1+Recombinant+Proteins+in+Escherichia+coli&rft.au=Qoronfleh%2C+M+W&rft.aulast=Qoronfleh&rft.aufirst=M&rft.date=1999-05-01&rft.volume=80&rft.issue=2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Applied+Biochemistry+and+Biotechnology&rft.issn=02732289&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Human immunodeficiency virus 1; Fermenters; Translation; Batch culture; Dissolved oxygen; Aerobic conditions; Fed-batch culture ER - TY - JOUR T1 - A Paracrine Paradigm for in Vivo Gene Therapy in the Central Nervous System: Treatment of Chronic Pain AN - 17300230; 4524651 AB - A limitation of current gene therapy efforts aimed at central nervous system disorders concerns distribution of vectors on direct injection into neural tissue. Here we have circumvented this problem by transferring genes to the meninges surrounding the spinal cord, achieving an in vivo gene transfer paradigm for treating chronic pain. The therapeutic vector consisted of a recombinant adenovirus encoding a secreted form of the potent endogenous opioid beta -endorphin. In an inflammation model of persistent pain, administration of the vector into the cerebrospinal fluid (CSF) surrounding the spinal cord transduced meningeal pia mater cells. The resulting increase in beta -endorphin secretion attenuated inflammatory hyperalgesia, yet had no effect on basal nociceptive responses. This demonstration of a gene transfer approach to pain treatment can be generalized to neurodegenerative disorcers in which broad spatial distribution of therapeutic effect is critical. JF - Human Gene Therapy AU - Finegold, A A AU - Mannes, A J AU - Iadarola, MJ AD - National Institutes of Health, National Institute of Dental and Craniosacral Research, Pain and Neurosensory Mechanisms Branch, Building 49, Room 1A11, 49 Convent Drive, MSC 4410, Bethesda, MD 20892-4410, USA, Michael.Iadarola@nih.gov Y1 - 1999/05/01/ PY - 1999 DA - 1999 May 01 SP - 1251 EP - 1257 VL - 10 IS - 7 SN - 1043-0342, 1043-0342 KW - beta -endorphins KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Central nervous system KW - Gene therapy KW - Pain KW - Inflammation KW - Neurodegenerative diseases KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17300230?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=A+Paracrine+Paradigm+for+in+Vivo+Gene+Therapy+in+the+Central+Nervous+System%3A+Treatment+of+Chronic+Pain&rft.au=Finegold%2C+A+A%3BMannes%2C+A+J%3BIadarola%2C+MJ&rft.aulast=Finegold&rft.aufirst=A&rft.date=1999-05-01&rft.volume=10&rft.issue=7&rft.spage=1251&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018238 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pain; Neurodegenerative diseases; Gene therapy; Central nervous system; Inflammation DO - http://dx.doi.org/10.1089/10430349950018238 ER - TY - JOUR T1 - Use of an Ethanol Sensor for Feedback Control of Growth and Expression of TBV25H in Saccharomyces cerevisiae AN - 17298735; 4561552 AB - A process for production of a malaria transmission blocking vaccine candidate under the control of the ADH2 promoter in Saccharomyces cerevisiae was developed. Monitoring and controlling the ethanol concentration during the process is essential for successful expression of the recombinant protein. A simple sensor accomplishing this task has been developed, the principle of its operation is the following: air-flow through silicone tubing submerged in the media picks up ethanol, which is detected by an alcohol sensor that relays a signal to a controller regulating the amount of ethanol added to the culture. The sensor was used successfully in high cell density cultures of various scales. JF - Biotechnology and Bioengineering AU - Noronha, S B AU - Wagner, L W AU - Matheson, N H AU - Shiloach, J AD - Biotechnology Unit, LCDB, NIDDK, NIH, Bethesda, Maryland 20892, USA Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 285 EP - 289 VL - 63 IS - 3 SN - 0006-3592, 0006-3592 KW - ADH2 gene KW - budding yeast KW - ethanol KW - Biotechnology and Bioengineering Abstracts; Agricultural and Environmental Biotechnology Abstracts KW - Sensors KW - Cell density KW - Malaria KW - Cell culture KW - Disease transmission KW - Saccharomyces cerevisiae KW - Vaccines KW - Feedback inhibition KW - W 30965:Miscellaneous, Reviews KW - W2 32220:Cell culture UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17298735?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biotechnology+and+Bioengineering&rft.atitle=Use+of+an+Ethanol+Sensor+for+Feedback+Control+of+Growth+and+Expression+of+TBV25H+in+Saccharomyces+cerevisiae&rft.au=Noronha%2C+S+B%3BWagner%2C+L+W%3BMatheson%2C+N+H%3BShiloach%2C+J&rft.aulast=Noronha&rft.aufirst=S&rft.date=1999-05-01&rft.volume=63&rft.issue=3&rft.spage=285&rft.isbn=&rft.btitle=&rft.title=Biotechnology+and+Bioengineering&rft.issn=00063592&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Cell culture; Disease transmission; Malaria; Sensors; Cell density; Feedback inhibition; Vaccines ER - TY - JOUR T1 - IL-12-Independent Costimulation Pathways for Interferon- gamma Production in Familial Disseminated Mycobacterium avium Complex Infection AN - 17296970; 4557369 AB - We have described previously a family with an apparent genetic susceptibility to disseminated Mycobacterium avium complex infection and an underlying defect in IL-12 regulation leading to abnormally low interferon- gamma production. Their T cells appear to act normally when in the presence of normal accessory cells. Cell-to-cell contact was necessary for normal monocytes to complement the familial patient monocyte defect, suggesting the familial defect in interferon- gamma costimulation involves pathways requiring cell surface molecule interactions. In an effort to better characterize the abnormality in these patients, we examined the role of known costimulatory molecules in residual costimulation by patient PBMC compared to normals. Whereas normals utilized CD40/CD40L interactions and IL-12 production for optimal interferon- gamma costimulation in PHA-stimulated cocultures, familial patient interferon- gamma production was low and unaffected by their blockade. CD86 blockade caused a greater than 50% reduction in both normal and familial patient interferon- gamma production, implying that a majority of residual familial patient costimulation required this pathway. Furthermore, selected myelomonocytic cell lines (K562 and THP1) acted as potent accessory cells for interferon- gamma production by familial patient and normal T cells, largely independent of IL-12 production. However, CD86 blockade of K562 cell/familial cell cocultures resulted in less than a 20% reduction in interferon- gamma production, indicating that familial patient cells respond to IL-12- and CD86-independent costimulatory signals for interferon- gamma as well. Thus, we demonstrate that the familial defect also involves interferon- gamma costimulation pathways requiring both CD40/CD40L interaction and IL-12 production, while residual pathways remain that allow low-level interferon- gamma production. Familial Mycobacterium avium patient monocytes and certain myelomonocytic cell lines can be exploited to investigate IL-12-independent costimulation for interferon- gamma production. JF - Clinical Immunology AU - Frucht, D M AU - Sandberg, DI AU - Brown, M R AU - Gerstberger, S M AU - Holland, S M AD - Building 10, Room 11N103, 10 Center Dr., MSC 1886, Bethesda, MD 20892-1886, USA, smh@nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 234 EP - 241 VL - 91 IS - 2 SN - 1521-6616, 1521-6616 KW - Mycobacterium avium KW - gamma -Interferon KW - immunology KW - man KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Interleukin 12 KW - Lymphocytes T KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17296970?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinical+Immunology&rft.atitle=IL-12-Independent+Costimulation+Pathways+for+Interferon-+gamma+Production+in+Familial+Disseminated+Mycobacterium+avium+Complex+Infection&rft.au=Frucht%2C+D+M%3BSandberg%2C+DI%3BBrown%2C+M+R%3BGerstberger%2C+S+M%3BHolland%2C+S+M&rft.aulast=Frucht&rft.aufirst=D&rft.date=1999-05-01&rft.volume=91&rft.issue=2&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Clinical+Immunology&rft.issn=15216616&rft_id=info:doi/10.1006%2Fclim.1999.4688 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium avium; Interleukin 12; Lymphocytes T DO - http://dx.doi.org/10.1006/clim.1999.4688 ER - TY - JOUR T1 - Sensitivity of spermidine-deficient Saccharomyces cerevisiae to paromomycin AN - 17251205; 4526438 AB - Spermidine-deficient Saccharomyces cerevisiae cells are much more sensitive to paromomycin than nondeficient cells, resulting in cessation of growth and cell death. JF - Antimicrobial Agents & Chemotherapy AU - Balasundaram, D AU - Tabor, C W AU - Tabor, H AD - NIH-NIDDK, Building 8, Room 225, Bethesda, MD 20892-0830, USA, tabor@helix.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 1314 EP - 1316 VL - 43 IS - 5 SN - 0066-4804, 0066-4804 KW - Paromomycin KW - Spermidine KW - budding yeast KW - paromomycin KW - spermidine KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Antifungal agents KW - Cell death KW - Drug sensitivity testing KW - Antibiotics KW - Saccharomyces cerevisiae KW - A 01095:Others KW - K 03063:Effects of physical & chemical factors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17251205?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+Agents+%26+Chemotherapy&rft.atitle=Sensitivity+of+spermidine-deficient+Saccharomyces+cerevisiae+to+paromomycin&rft.au=Balasundaram%2C+D%3BTabor%2C+C+W%3BTabor%2C+H&rft.aulast=Balasundaram&rft.aufirst=D&rft.date=1999-05-01&rft.volume=43&rft.issue=5&rft.spage=1314&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+Agents+%26+Chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Saccharomyces cerevisiae; Cell death; Drug sensitivity testing; Antibiotics; Antifungal agents ER - TY - JOUR T1 - Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers AN - 17245916; 4526333 AB - Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN- gamma ) responses in mice correlate with clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN- gamma and additional cytokine genes in patients who had recent-onset Chlamydia-associated arthritis (Chl-AA). IL-10 and IFN- gamma mRNA were relatively abundant in recent-onset Chl-AA. JF - Infection and Immunity AU - Kotake, S AU - Schumacher, HR Jr AU - Arayssi, T K AU - Gerard, H C AU - Branigan, P J AU - Hudson AU - Yarboro, CH AU - Klippel, J H AU - Wilder, R L AD - ARB, NIAMS, NIH, 10 Center Dr. MSC 1820, Bldg. 10, Rm. 9N228, Bethesda, MD 20892-1820, USA, wilderr@arb.niams.hih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2682 EP - 2686 VL - 65 IS - 5 SN - 0019-9567, 0019-9567 KW - Chlamydia KW - gamma -Interferon KW - mice KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Interleukin 10 KW - Gene expression KW - Synovial fluid KW - Arthritis KW - Pneumonitis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17245916?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Gamma+interferon+and+interleukin-10+gene+expression+in+synovial+tissues+from+patients+with+early+stages+of+Chlamydia-associated+arthritis+and+undifferentiated+oligoarthritis+and+from+healthy+volunteers&rft.au=Kotake%2C+S%3BSchumacher%2C+HR+Jr%3BArayssi%2C+T+K%3BGerard%2C+H+C%3BBranigan%2C+P+J%3BHudson%3BYarboro%2C+CH%3BKlippel%2C+J+H%3BWilder%2C+R+L&rft.aulast=Kotake&rft.aufirst=S&rft.date=1999-05-01&rft.volume=65&rft.issue=5&rft.spage=2682&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia; Gene expression; Interleukin 10; Pneumonitis; Synovial fluid; Arthritis ER - TY - JOUR T1 - Insertional inactivation of genes responsible for the D-alanylation of lipoteichoic acid in Streptococcus gordonii DL1 (Challis) affects intrageneric coaggregations AN - 17243432; 4526295 AB - Most human oral viridans streptococci participate in intrageneric coaggregations, the cell-to-cell adherence among genetically distinct streptococci. Two genes relevant to these intrageneric coaggregations were identified by transposon Tn916 mutagenesis of Streptococcus gordonii DL1 (Challis). A 626-bp sequence flanking the left end of the transposon was homologous to dltA and dltB of Lactobacillus rhamnosus ATCC 7469 (formerly called Lactobacillus casei). A 60-kb probe based on this flanking sequence was used to identify the homologous DNA in a fosmid library of S. gordonii DL1. This DNA encoded D-alanine-D-alanyl carrier protein ligase that was expressed in Escherichia coli from the fosmid clone. The cloned streptococcal dltA was disrupted by inserting an ermAM cassette, and then it was linearized and transformed into S. gordonii DL1 for allelic replacement. Erythromycin-resistant transformants containing a single insertion in dltA exhibited a loss of D-alanyl esters in lipoteichoic acid (LTA) and a loss of intrageneric coaggregation. This phenotype was correlated with the loss of a 100-kDa surface protein reported previously to be involved in mediating intrageneric coaggregation (C.J. Whittaker, D.L. Clemans, and P.E. Kolenbrander, Infect. Immun. 64:4137-4142, 1996). The mutants retained the parental ability to participate in intergeneric coaggregation with human oral actinomyces, indicating the specificity of the mutation in altering intrageneric coaggregations. The mutants were altered morphologically and exhibited aberrant cell septa in a variety of pleomorphs. The natural DNA transformation frequency was reduced 10-fold in these mutants. Southern analysis of chromosomal DNAs from various streptococcal species with the dltA probe revealed the presence of this gene in most viridans streptococci. Thus, it is hypothesized that D-alanyl LTA may provide binding sites for the putative 100-kDa adhesin and scaffolding for the proper presentation of this adhesin to mediate intrageneric coaggregation. JF - Infection and Immunity AU - Clemans, D L AU - Kolenbrander, P E AU - Debabov, D V AU - Zhang, Q AU - Lunsford, R D AU - Sakone, H AU - Whittaker, C J AU - Heaton, M P AU - Neuhaus, F C AD - National Institutes of Health, Bldg. 30, Rm. 310, 30 Convent Dr., MSC 4350, Bethesda, MD 20892-4350, USA, pkolenbrander@dir.nidcr.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2464 EP - 2474 VL - 65 IS - 5 SN - 0019-9567, 0019-9567 KW - Lipoteichoic acid KW - Transposon Tn916 KW - dltA gene KW - dltB gene KW - lipoteichoic acid KW - mutants KW - nucleotide sequence KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts KW - Southern blotting KW - Gene disruption KW - Aggregation KW - Membrane proteins KW - Phenotypes KW - Lactobacillus rhamnosus KW - Mutagenesis KW - Streptococcus gordonii KW - Cell aggregation KW - Gene libraries KW - Escherichia coli KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17243432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Insertional+inactivation+of+genes+responsible+for+the+D-alanylation+of+lipoteichoic+acid+in+Streptococcus+gordonii+DL1+%28Challis%29+affects+intrageneric+coaggregations&rft.au=Clemans%2C+D+L%3BKolenbrander%2C+P+E%3BDebabov%2C+D+V%3BZhang%2C+Q%3BLunsford%2C+R+D%3BSakone%2C+H%3BWhittaker%2C+C+J%3BHeaton%2C+M+P%3BNeuhaus%2C+F+C&rft.aulast=Clemans&rft.aufirst=D&rft.date=1999-05-01&rft.volume=65&rft.issue=5&rft.spage=2464&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Lactobacillus rhamnosus; Streptococcus gordonii; Mutagenesis; Aggregation; Gene disruption; Phenotypes; Gene libraries; Cell aggregation; Membrane proteins; Southern blotting ER - TY - JOUR T1 - The C-Terminal Domain of DnaQ Contains the Polymerase Binding Site AN - 17227814; 4508634 AB - The Escherichia coli dnaQ gene encodes the 3' arrow right 5' exonucleolytic proofreading ( epsilon ) subunit of DNA polymerase III (Pol III). Genetic analysis of dnaQ mutants has suggested that epsilon might consist of two domains, an N-terminal domain containing the exonuclease and a C-terminal domain essential for binding the polymerase ( alpha ) subunit. We have created truncated forms of dnaQ resulting in epsilon subunits that contain either the N-terminal or the C-terminal domain. Using the yeast two-hybrid system we analyzed the interactions of the single- domain epsilon subunits with the alpha and theta subunits of the Pol III core. The DnaQ991 protein consisting of the N-terminal 186 amino acids, was defective in binding to the alpha subunit while retaining normal binding to the theta subunit. In contrast, the N Delta 186 protein, consisting of the C-terminal 57 amino acids, exhibited normal binding to the alpha subunit but was defective in binding to the theta subunit. A strain carrying the dnaQ991 allele exhibited a strong, recessive mutator phenotype, as expected from a defective alpha binding mutant. The data are consistent with the existence of two functional domains in epsilon , with the C-terminal domain responsible for polymerase binding. JF - Journal of Bacteriology AU - Taft-Benz, SA AU - Schaaper, R M AD - NIEHS Laboratory of Molecular Genetics, MD E3-01, P.O. Box 12233, 111 T.W. Alexander Dr., Research Triangle Park, NC 27709, schaaper@niehs.nih.gov Y1 - 1999/05// PY - 1999 DA - May 1999 SP - 2963 EP - 2965 VL - 181 IS - 9 SN - 0021-9193, 0021-9193 KW - DnaQ protein KW - amino acid sequence prediction KW - dnaQ gene KW - mutators KW - nucleotide sequence KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Deletion mutant KW - DNA-directed DNA polymerase KW - Escherichia coli KW - Proofreading KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17227814?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=The+C-Terminal+Domain+of+DnaQ+Contains+the+Polymerase+Binding+Site&rft.au=Taft-Benz%2C+SA%3BSchaaper%2C+R+M&rft.aulast=Taft-Benz&rft.aufirst=SA&rft.date=1999-05-01&rft.volume=181&rft.issue=9&rft.spage=2963&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Deletion mutant; Proofreading; DNA-directed DNA polymerase ER - TY - JOUR T1 - The structural basis of ordered substrate binding by serotonin N-acetyltransferase: enzyme complex at 1.8 A resolution with a bisubstrate analog. AN - 69744524; 10319816 AB - Serotonin N-acetyltransferase, a member of the GNAT acetyltransferase superfamily, is the penultimate enzyme in the conversion of serotonin to melatonin, the circadian neurohormone. Comparison of the structures of the substrate-free enzyme and the complex with a bisubstrate analog, coenzyme A-S-acetyltryptamine, demonstrates that acetyl coenzyme A (AcCoA) binding is accompanied by a large conformational change that in turn leads to the formation of the serotonin-binding site. The structure of the complex also provides insight into how the enzyme may facilitate acetyl transfer. A water-filled channel leading from the active site to the surface provides a pathway for proton removal following amine deprotonation. Furthermore, structural and mutagenesis results indicate an important role for Tyr-168 in catalysis. JF - Cell AU - Hickman, A B AU - Namboodiri, M A AU - Klein, D C AU - Dyda, F AD - Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-0560, USA. Y1 - 1999/04/30/ PY - 1999 DA - 1999 Apr 30 SP - 361 EP - 369 VL - 97 IS - 3 SN - 0092-8674, 0092-8674 KW - Tryptamines KW - 0 KW - N-acetyltryptamine KW - 1016-47-3 KW - Acetyl Coenzyme A KW - 72-89-9 KW - Acetylserotonin O-Methyltransferase KW - EC 2.1.1.4 KW - Arylamine N-Acetyltransferase KW - EC 2.3.1.5 KW - Melatonin KW - JL5DK93RCL KW - Index Medicus KW - Tryptamines -- metabolism KW - Animals KW - Protein Structure, Secondary KW - Sheep KW - Mutagenesis -- physiology KW - Binding Sites -- physiology KW - Acetyl Coenzyme A -- chemistry KW - Cloning, Molecular KW - Acetylation KW - Acetylserotonin O-Methyltransferase -- metabolism KW - Melatonin -- biosynthesis KW - Molecular Sequence Data KW - Substrate Specificity KW - Acetyl Coenzyme A -- metabolism KW - Acetylserotonin O-Methyltransferase -- chemistry KW - Tryptamines -- chemistry KW - Catalysis KW - Arylamine N-Acetyltransferase -- chemistry KW - Arylamine N-Acetyltransferase -- metabolism KW - Arylamine N-Acetyltransferase -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69744524?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=The+structural+basis+of+ordered+substrate+binding+by+serotonin+N-acetyltransferase%3A+enzyme+complex+at+1.8+A+resolution+with+a+bisubstrate+analog.&rft.au=Hickman%2C+A+B%3BNamboodiri%2C+M+A%3BKlein%2C+D+C%3BDyda%2C+F&rft.aulast=Hickman&rft.aufirst=A&rft.date=1999-04-30&rft.volume=97&rft.issue=3&rft.spage=361&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1CJW; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modelling long-term contaminant migration in a catchment at fine spatial and temporal scales using the UP system AN - 17215204; 4505165 AB - A method has been developed to simulate the long-term migration of radionuclides in the near-surface of a river catchment, following their release from a deep underground repository for radioactive waste. Previous (30-year) simulations, conducted using the SHETRAN physically based modelling system, showed that long-term (many decades) simulations are required to allow the system to reach steady state. Physically based, distributed models, such as SHETRAN, tend to be too computationally expensive for this task. Traditional lumped catchment-scale models, on the other hand, do not give sufficiently detailed spatially distributed results. An intermediate approach to modelling has therefore been developed which allows flow and transport processes to be simulated with the spatial resolution normally associated with distributed models, whilst being computationally efficient. The approach involves constructing a lumped model in which the catchment is represented by a number of conceptual water storage compartments. The flow rates to and from these compartments are prescribed by functions that summarize the results from physically based distributed models run for a range of characteristic flow regimes. The physically based models used were, SHETRAN for the subsurface compartments, a particle tracking model for overland flow and an analytical model for channel routing. One important advantage of the method used in constructing the lumped model is that it makes down scaling possible, in the sense that fine-scale information on the distributed hydrological regime, as simulated by the physically based distributed models, can be inferred from the variables in the lumped model that describe the hydrology at the catchment scale. A 250-year flow simulation has been run and the down scaling process used to infer a 250-year time-series of three-dimensional velocity fields for the subsurface of the catchment. This series was then used to drive a particle tracking simulation of contaminant migration. The concentration and spatial distribution of contaminants simulated by this model for the first 30 years were in close agreement with SHETRAN results. The remaining 220 years highlighted the fact that some of the most important transport pathways to the surface carry contaminants only very slowly so both the magnitude and spatial distribution of concentration in surface soils are not apparent over the shorter SHETRAN simulations. JF - Hydrological Processes AU - Sloan, W T AU - Ewen, J AD - Department of Civil Engineering, Cassie Building, University of Newcastle, Newcastle upon Tyne, NEI 7RU, UK. Y1 - 1999/04/30/ PY - 1999 DA - 1999 Apr 30 SP - 823 EP - 846 PB - John Wiley & Sons VL - 13 IS - 6 SN - 0885-6087, 0885-6087 KW - Pollution Abstracts; Water Resources Abstracts KW - Path of pollutants KW - Spatial distribution KW - Contamination KW - Pollution dispersion KW - Radioactive wastes KW - Hydrologic data KW - Migration KW - Flow rates KW - Catchment areas KW - Radioisotopes KW - Catchments KW - Hydrology KW - P 2000:FRESHWATER POLLUTION KW - SW 3020:Sources and fate of pollution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17215204?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Apollution&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hydrological+Processes&rft.atitle=Modelling+long-term+contaminant+migration+in+a+catchment+at+fine+spatial+and+temporal+scales+using+the+UP+system&rft.au=Sloan%2C+W+T%3BEwen%2C+J&rft.aulast=Sloan&rft.aufirst=W&rft.date=1999-04-30&rft.volume=13&rft.issue=6&rft.spage=823&rft.isbn=&rft.btitle=&rft.title=Hydrological+Processes&rft.issn=08856087&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2015-03-24 N1 - SubjectsTermNotLitGenreText - Contamination; Spatial distribution; Pollution dispersion; Radioactive wastes; Catchments; Radioisotopes; Hydrology; Migration; Flow rates; Path of pollutants; Catchment areas; Hydrologic data ER - TY - JOUR T1 - Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide from Shigella dysenteriae type 1 AN - 17223976; 4508564 AB - Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical (protective) level of serum IgG to the O-specific polysaccharide (O-SP) domain of Shigella lipopolysaccharide (LPS) confers immunity. The O-SP is a hapten and must be conjugated to a protein to induce serum antibodies. The O-SP of Shigella dysenteriae type 1 (~27 tetrasaccharide repeat units), prepared by acid hydrolysis of the LPS, was bound to human serum albumin (HSA) by multiple point attachment (O-SP- HSA): The molar ratio of HSA to O-SP was 1.0. Synthetic saccharides, composed of one or multiples of the O-SP tetrasaccharide, equipped with a spacer at their reducing end, were bound to HSA by a single point attachment: The average molar ratios of the saccharides to HSA ranged from 4 to 24. Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra- octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA. Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 mu g of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P = 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide/HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned. JF - Proceedings of the National Academy of Sciences, USA AU - Pozsgay, V AU - Chu, C AU - Pannell, L AU - Wolfe, J AU - Robbins, J B AU - Schneerson, R AD - Laboratory of Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2720 USA Y1 - 1999/04/27/ PY - 1999 DA - 1999 Apr 27 SP - 5194 EP - 5197 VL - 96 IS - 09 SN - 0027-8424, 0027-8424 KW - Shigella dysenteriae KW - mice KW - polysaccharides KW - saccharides KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Immunoglobulin G KW - Antibody response KW - Vaccines KW - J 02834:Vaccination and immunization KW - F 06807:Active immunization UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17223976?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Protein+conjugates+of+synthetic+saccharides+elicit+higher+levels+of+serum+IgG+lipopolysaccharide+antibodies+in+mice+than+do+those+of+the+O-specific+polysaccharide+from+Shigella+dysenteriae+type+1&rft.au=Pozsgay%2C+V%3BChu%2C+C%3BPannell%2C+L%3BWolfe%2C+J%3BRobbins%2C+J+B%3BSchneerson%2C+R&rft.aulast=Pozsgay&rft.aufirst=V&rft.date=1999-04-27&rft.volume=96&rft.issue=09&rft.spage=5194&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Shigella dysenteriae; Immunoglobulin G; Vaccines; Antibody response ER - TY - JOUR T1 - In vivo determination of striatal dopamine D2 receptor occupancy in patients treated with olanzapine. AN - 70019917; 10482380 AB - In vivo studies of dopamine D2 receptor occupancy with atypical antipsychotics have suggested good clinical efficacy at occupancy rates less than those observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D2 occupancy. We used [123I]IBZM-SPECT to investigate striatal D2 receptor occupancy in 10 schizophrenic patients who were treated with both a low (5 mg) and a high dose (20 mg) of the novel antipsychotic olanzapine without concomitant medications. The mean D2 occupancy at 5 mg was 59.8% (range 33-81%); the mean D2 occupancy at 20 mg was 82.8% (range 56-97%). Although the D2 occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no significant differences in clinical ratings for psychiatric symptoms or extrapyramidal side effects between the two doses of olanzapine. These data suggest that: (1) olanzapine doses below those used routinely occupy D2 receptors at levels approaching those associated with therapeutic response; (2) higher doses produce relatively high levels of D2 occupancy rates; and (3) EPS are mild even at relatively high levels of D2 occupancy. JF - Psychiatry research AU - Raedler, T J AU - Knable, M B AU - Lafargue, T AU - Urbina, R A AU - Egan, M F AU - Pickar, D AU - Weinberger, D R AD - Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20892, USA. Y1 - 1999/04/26/ PY - 1999 DA - 1999 Apr 26 SP - 81 EP - 90 VL - 90 IS - 2 SN - 0165-1781, 0165-1781 KW - Benzamides KW - 0 KW - Contrast Media KW - Pyrrolidines KW - Receptors, Dopamine D2 KW - Serotonin Uptake Inhibitors KW - Benzodiazepines KW - 12794-10-4 KW - Pirenzepine KW - 3G0285N20N KW - 3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide KW - 84226-06-2 KW - olanzapine KW - N7U69T4SZR KW - Index Medicus KW - Parkinson Disease, Secondary -- chemically induced KW - Tomography, Emission-Computed, Single-Photon KW - Dose-Response Relationship, Drug KW - Humans KW - Adult KW - Case-Control Studies KW - Male KW - Female KW - Schizophrenia -- metabolism KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Corpus Striatum -- metabolism KW - Pirenzepine -- analogs & derivatives KW - Schizophrenia -- diagnostic imaging KW - Serotonin Uptake Inhibitors -- adverse effects KW - Receptors, Dopamine D2 -- metabolism KW - Corpus Striatum -- diagnostic imaging KW - Pirenzepine -- pharmacology KW - Corpus Striatum -- drug effects KW - Receptors, Dopamine D2 -- drug effects KW - Schizophrenia -- drug therapy KW - Serotonin Uptake Inhibitors -- pharmacology KW - Pirenzepine -- therapeutic use KW - Pirenzepine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/70019917?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychiatry+research&rft.atitle=In+vivo+determination+of+striatal+dopamine+D2+receptor+occupancy+in+patients+treated+with+olanzapine.&rft.au=Raedler%2C+T+J%3BKnable%2C+M+B%3BLafargue%2C+T%3BUrbina%2C+R+A%3BEgan%2C+M+F%3BPickar%2C+D%3BWeinberger%2C+D+R&rft.aulast=Raedler&rft.aufirst=T&rft.date=1999-04-26&rft.volume=90&rft.issue=2&rft.spage=81&rft.isbn=&rft.btitle=&rft.title=Psychiatry+research&rft.issn=01651781&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-10-21 N1 - Date created - 1999-10-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Evaluation of toxicity of beta-tethymustine, a new anticancer compound, in mice. AN - 69838468; 10378781 AB - The toxicity of beta-tethymustine, a potential anticancer compound 1 ((Cancer Lett., 119 (1997) 7-12) was assessed in normal as well as in Ehrlich ascites carcinoma (EAC), Sarcoma-180 (S-180) and Dalton' s Lymphoma (DL) tumour-bearing Swiss male mice by measuring drug-induced changes in haematological parameters, femoral bone marrow cellularity and splenic cellularity on days 9, 15 and 21 following drug treatment at the optimum dose of 8.0 mg/kg body weight from days 1 to 7. Detailed studies were also made by noting sequential changes in the above parameters in normal and EAC-bearing mice on days 12 and 18, respectively. The results indicate that the compound did not adversely affect haematopoiesis as it was observed that no significant decrease in haematological parameters and femoral marrow cellularity occurred in treated groups. Initial hyposplenic activity was, however, noted in EAC and normal treated groups on day 9 which soon reached normal count within 7-10 days after termination of drug therapy. Drug-induced hepatotoxicity and nephrotoxicity were also sequentially evaluated in normal and tumour-bearing mice on days 9, 15 and 21 but no such toxicities were detected. Also, body weight, skin and hair texture, and behavioural pattern (food and water intake and activity) did not reflect any toxic reaction in host mice at this optimum dose. JF - Cancer letters AU - Ghosh, M AU - Sadhu, U AU - Bhattacharya, S AU - Dutta, S AU - Bhattacharya, B AU - Sanyal, U AD - Department of Anticancer Drug Development & Chemotherapy, Chittaranjan National Cancer Institute, Calcutta, India. Y1 - 1999/04/26/ PY - 1999 DA - 1999 Apr 26 SP - 107 EP - 114 VL - 138 IS - 1-2 SN - 0304-3835, 0304-3835 KW - Antineoplastic Agents KW - 0 KW - Hemoglobins KW - Imidazoles KW - Imidazolidines KW - Naphthalenes KW - beta-tethymustine KW - Index Medicus KW - Animals KW - Hemoglobins -- analysis KW - Liver -- drug effects KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Kidney -- drug effects KW - Mice KW - Carcinoma, Ehrlich Tumor -- blood KW - Spleen -- drug effects KW - Male KW - Blood Cell Count -- drug effects KW - Imidazoles -- toxicity KW - Antineoplastic Agents -- toxicity KW - Naphthalenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69838468?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+letters&rft.atitle=Evaluation+of+toxicity+of+beta-tethymustine%2C+a+new+anticancer+compound%2C+in+mice.&rft.au=Ghosh%2C+M%3BSadhu%2C+U%3BBhattacharya%2C+S%3BDutta%2C+S%3BBhattacharya%2C+B%3BSanyal%2C+U&rft.aulast=Ghosh&rft.aufirst=M&rft.date=1999-04-26&rft.volume=138&rft.issue=1-2&rft.spage=107&rft.isbn=&rft.btitle=&rft.title=Cancer+letters&rft.issn=03043835&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cognitive performance in (+) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy) users: a controlled study AN - 17576971; 4502743 AB - (+) 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy) is an amphetamine analog and drug of abuse. In animals, MDMA damages brain serotonin (5-HT) neurons at doses that overlap with those used recreationally by some humans. To date, few functional sequelae of MDMA-induced 5-HT damage have been identified. Since serotonin is thought to be involved in cognitive processes, and since previous studies have reported verbal and visual memory deficits in MDMA users, the present study sought to determine whether other cognitive processes are influenced by previous exposure to MDMA. Twenty-two MDMA users who had not used MDMA for at least 3 weeks and 23 control subjects were tested repeatedly with a computerized cognitive performance assessment battery while participating in a 5-day controlled inpatient study. Cerebrospinal fluid (CSF) measures of monoamine metabolites were also collected as an index of brain monoaminergic function. MDMA users and controls were found to perform similarly on several cognitive tasks. However, MDMA subjects had significant performance deficits on a sustained attention task requiring arithmetic calculations, a task requiring complex attention and incidental learning, a task requiring short term memory and a task of semantic recognition and verbal reasoning. MDMA users also had significant selective decreases in CSF 5-HIAA. The present CSF data provide further evidence that MDMA is neurotoxic to brain 5-HT neurons in humans, and the behavioral data suggest that brain 5-HT injury is associated with subtle, but significant, cognitive deficits. JF - Psychopharmacology AU - McCann, U D AU - Mertl, M AU - Eligulashvili, V AU - Ricaurte, G A AD - Unit on Anxiety, Biological Psychiatry Branch, NIMH, Bethesda, MD 20892-1272, USA Y1 - 1999/04/26/ PY - 1999 DA - 1999 Apr 26 SP - 417 EP - 425 PB - Springer-Verlag VL - 143 IS - 4 SN - 0033-3158, 0033-3158 KW - Toxicology Abstracts; CSA Neurosciences Abstracts KW - Man KW - Brain KW - Drug abuse KW - MDMA KW - Serotonin KW - Cognitive ability KW - Neurotoxicity KW - N3 11106:Neurobiology of drug abuse KW - X 24180:Social poisons & drug abuse UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17576971?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Cognitive+performance+in+%28%2B%29+3%2C4-methylenedioxymethamphetamine+%28MDMA%2C+%22ecstasy%29+users%3A+a+controlled+study&rft.au=McCann%2C+U+D%3BMertl%2C+M%3BEligulashvili%2C+V%3BRicaurte%2C+G+A&rft.aulast=McCann&rft.aufirst=U&rft.date=1999-04-26&rft.volume=143&rft.issue=4&rft.spage=417&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Drug abuse; Cognitive ability; MDMA; Serotonin; Neurotoxicity; Brain; Man ER - TY - JOUR T1 - Crystal Structure of Cyanovirin-N, a Potent HIV-inactivating Protein, Shows Unexpected Domain Swapping AN - 17222511; 4500944 AB - The crystal structure of cyanovirin-N (CV-N), a protein with potent antiviral activity, was solved at 1.5 Aa resolution by molecular replacement using as the search model the solution structure previously determined by NMR. The crystals belong to the space group P3 sub(2)21 with one monomer of CV-N in each asymmetric unit. The primary structure of CV-N contains 101 residues organized in two domains, A (residues 1 to 50) and B (residues 51 to 101), with a high degree of internal sequence and structural similarity. We found that under the conditions of the crystallographic experiments (low pH and 26 % isopropanol), two symmetrically related monomers form a dimer by domain swapping, such that domain A of one monomer interacts with domain B' of its crystallographic symmetry mate and vice versa. Because the two swapped domains are distant from each other, domain swapping does not result in additional intramolecular interactions. Even though one of the protein sample solutions that was used for crystallization clearly contained 100 % monomeric CV-N molecules, as judged by various methods, we were only able to obtain crystals containing domain-swapped dimers. With the exception of the unexpected phenomenon of domain swapping, the crystal structure of CV-N is very similar to the NMR structure, with a root-mean-square deviation of 0.55 Aa for the main-chain atoms, the best agreement reported to date for structures solved using both techniques. JF - Journal of Molecular Biology AU - Yang, F AU - Bewley, CA AU - Louis, J M AU - Gustafson, K R AU - Boyd, M R AU - Gronenborn, A M AU - Clore, G M AU - Wlodawer, A AD - Macromolecular Structure Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, 21702-1201, MD, USA Y1 - 1999/04/26/ PY - 1999 DA - 1999 Apr 26 SP - 403 EP - 412 PB - Academic Press VL - 288 IS - 3 SN - 0022-2836, 0022-2836 KW - HIV KW - amino acid sequence KW - cyanovirin-N KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts KW - Acquired immune deficiency syndrome KW - Antiviral agents KW - Human immunodeficiency virus KW - Crystal structure KW - N.M.R. KW - A 01002:Acids, amino acids, peptides & proteins KW - V 22002:AIDS: Molecular and in vitro aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17222511?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Molecular+Biology&rft.atitle=Crystal+Structure+of+Cyanovirin-N%2C+a+Potent+HIV-inactivating+Protein%2C+Shows+Unexpected+Domain+Swapping&rft.au=Yang%2C+F%3BBewley%2C+CA%3BLouis%2C+J+M%3BGustafson%2C+K+R%3BBoyd%2C+M+R%3BGronenborn%2C+A+M%3BClore%2C+G+M%3BWlodawer%2C+A&rft.aulast=Yang&rft.aufirst=F&rft.date=1999-04-26&rft.volume=288&rft.issue=3&rft.spage=403&rft.isbn=&rft.btitle=&rft.title=Journal+of+Molecular+Biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus; N.M.R.; Acquired immune deficiency syndrome; Antiviral agents; Crystal structure ER - TY - JOUR T1 - Criteria and recommendations for vitamin C intake. AN - 69713120; 10217058 AB - Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences. Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, extensive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bioavailability, urine excretion, adverse effects, biochemical and molecular function in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of deficiency. We applied these criteria to the Food and Nutrition Board's new guidelines, the Dietary Reference Intakes, which include 4 reference values. The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group. Based on an EAR of 100 mg/d of vitamin C, the RDA is proposed to be 120 mg/d. If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety. The final classification, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all individuals in the population. This amount is proposed to be less than 1 g of vitamin C daily. Physicians can tell patients that 5 servings of fruits and vegetables per day may be beneficial in preventing cancer and providing sufficient vitamin C intake for healthy people, and that 1 g or more of vitamin C may have adverse consequences in some people. JF - JAMA AU - Levine, M AU - Rumsey, S C AU - Daruwala, R AU - Park, J B AU - Wang, Y AD - Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/04/21/ PY - 1999 DA - 1999 Apr 21 SP - 1415 EP - 1423 VL - 281 IS - 15 SN - 0098-7484, 0098-7484 KW - Antioxidants KW - 0 KW - Free Radical Scavengers KW - Ascorbic Acid KW - PQ6CK8PD0R KW - Abridged Index Medicus KW - Index Medicus KW - Vegetables KW - Humans KW - Fruit KW - Biological Availability KW - Ascorbic Acid -- administration & dosage KW - Nutrition Policy KW - Ascorbic Acid -- adverse effects KW - Ascorbic Acid -- pharmacokinetics KW - Ascorbic Acid -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69713120?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=JAMA&rft.atitle=Criteria+and+recommendations+for+vitamin+C+intake.&rft.au=Levine%2C+M%3BRumsey%2C+S+C%3BDaruwala%2C+R%3BPark%2C+J+B%3BWang%2C+Y&rft.aulast=Levine&rft.aufirst=M&rft.date=1999-04-21&rft.volume=281&rft.issue=15&rft.spage=1415&rft.isbn=&rft.btitle=&rft.title=JAMA&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-28 N1 - Date created - 1999-04-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: JAMA. 1999 Dec 8;282(22):2118-9 [10591326] JAMA. 1999 Dec 8;282(22):2118; author reply 2119 [10591325] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism? AN - 69710487; 10218509 AB - Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994; it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked (one pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend or = 17 years of age versus < or = 12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m]2) was inversely associated with risk among women (P<.001). Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis. JF - Journal of the National Cancer Institute AU - Frisch, M AU - Glimelius, B AU - Wohlfahrt, J AU - Adami, H O AU - Melbye, M AD - Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen. frischm@mail.nih.gov Y1 - 1999/04/21/ PY - 1999 DA - 1999 Apr 21 SP - 708 EP - 715 VL - 91 IS - 8 SN - 0027-8874, 0027-8874 KW - Gonadal Steroid Hormones KW - 0 KW - Index Medicus KW - Odds Ratio KW - Sex Factors KW - Humans KW - Aged KW - Body Mass Index KW - Risk KW - Postmenopause KW - Aged, 80 and over KW - Logistic Models KW - Risk Factors KW - Adult KW - Case-Control Studies KW - Menarche KW - Denmark KW - Middle Aged KW - Female KW - Male KW - Sweden KW - Anus Neoplasms -- metabolism KW - Anus Neoplasms -- etiology KW - Premenopause KW - Smoking -- metabolism KW - Smoking -- adverse effects KW - Gonadal Steroid Hormones -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69710487?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+National+Cancer+Institute&rft.atitle=Tobacco+smoking+as+a+risk+factor+in+anal+carcinoma%3A+an+antiestrogenic+mechanism%3F&rft.au=Frisch%2C+M%3BGlimelius%2C+B%3BWohlfahrt%2C+J%3BAdami%2C+H+O%3BMelbye%2C+M&rft.aulast=Frisch&rft.aufirst=M&rft.date=1999-04-21&rft.volume=91&rft.issue=8&rft.spage=708&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+National+Cancer+Institute&rft.issn=00278874&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-30 N1 - Date created - 1999-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats. AN - 69753130; 10327171 AB - NMDA receptor mediated excitotoxicity contributes substantially to aminoglycoside antibiotic-induced cochlear damage. Since vestibular as well as cochlear hair cells have glutamatergic synapses, aminoglycoside-induced vestibulotoxicity may also have an excitotoxic component. This hypothesis was tested by examining the effects of the uncompetitive NMDA receptor antagonist dizocilpine on streptomycin-induced vestibulotoxicity. Streptomycin-treated rats exhibited almost complete destruction of sensory hair cells in the crista ampullaris, vestibular impairment in the drop test, and hyperkinesia. Concurrent treatment with dizocilpine not only rescued a substantial population of sensory hair cells in the cristae, but prevented the attendant hyperkinesis and vestibular impairments. These results indicate that excitotoxic mechanisms contribute to aminoglycoside-induced vestibulotoxicity and that NMDA antagonists may be useful in attenuating aminoglycoside ototoxicity. JF - Neuroscience letters AU - Basile, A S AU - Brichta, A M AU - Harris, B D AU - Morse, D AU - Coling, D AU - Skolnick, P AD - Neuroscience Group, Laboratory of Bio-Organic Chemistry, NIDDK, NIH, Bethesda, MD, USA. asbasile@helix.nih.gov Y1 - 1999/04/16/ PY - 1999 DA - 1999 Apr 16 SP - 71 EP - 74 VL - 265 IS - 2 SN - 0304-3940, 0304-3940 KW - Anti-Bacterial Agents KW - 0 KW - Excitatory Amino Acid Antagonists KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - Streptomycin KW - Y45QSO73OB KW - Index Medicus KW - Space life sciences KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Hair Cells, Auditory -- ultrastructure KW - Hair Cells, Auditory -- drug effects KW - Male KW - Microscopy, Electron, Scanning KW - Streptomycin -- poisoning KW - Streptomycin -- antagonists & inhibitors KW - Vestibule, Labyrinth -- ultrastructure KW - Vestibule, Labyrinth -- drug effects KW - Anti-Bacterial Agents -- pharmacology KW - Anti-Bacterial Agents -- antagonists & inhibitors KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Dizocilpine Maleate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69753130?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Dizocilpine+attenuates+streptomycin-induced+vestibulotoxicity+in+rats.&rft.au=Basile%2C+A+S%3BBrichta%2C+A+M%3BHarris%2C+B+D%3BMorse%2C+D%3BColing%2C+D%3BSkolnick%2C+P&rft.aulast=Basile&rft.aufirst=A&rft.date=1999-04-16&rft.volume=265&rft.issue=2&rft.spage=71&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gene structure and chromosomal localization of mouse cyclin G2 (Ccng2). AN - 69710911; 10216255 AB - Cyclins are essential activators of cyclin-dependent kinases (Cdk) which, in turn, play pivotal roles in controlling transition through cell-cycle checkpoints. Cyclin G2 is a recently discovered second member of the G-type cyclins. The two members of the G-type cyclins, cyclin G1 and cyclin G2, share high structural similarity but their function remains to be defined. Here we characterize the structure of the mouse cyclin G2 gene by first cloning and sequencing the full-length mouse cyclin G2 cDNA. The cyclin G2 cDNA was used to isolate the cyclin G2 gene from a BAC library and to establish that the gene was transcribed from eight exons spanning a total of 8604bp. The cyclin G2 gene was mapped by fluorescence in situ hybridization (FISH) to mouse chromosome 5E3.3.-F1.3. This region is syntenic to a region on human chromosome 4. The expression of cyclins G1 and G2 was examined in various tissues, but no correlation between expression patterns of the two genes was observed. However, during hepatic ontogenesis the cyclin G2 expression level decreased with age, whereas cyclin G1 expression increased. Transient expression of cyclin G2-green fluorescent protein (GFP) fusion protein in NIH3T3 cells showed that cyclin G2 is essentially a cytoplasmic protein, in contrast to the largely nuclear localization of cyclin G1. Our data suggest that, despite the close structural similarity between mouse cyclins G1 and G2, these proteins most likely perform distinct functions. JF - Gene AU - Jensen, M R AU - Audolfsson, T AU - Keck, C L AU - Zimonjic, D B AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/04/16/ PY - 1999 DA - 1999 Apr 16 SP - 171 EP - 180 VL - 230 IS - 2 SN - 0378-1119, 0378-1119 KW - CCNG2 protein, human KW - 0 KW - Ccng2 protein, mouse KW - Cyclin G2 KW - Cyclins KW - DNA, Complementary KW - Luminescent Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - DNA, Complementary -- isolation & purification KW - Mice KW - Amino Acid Sequence KW - Chromosome Mapping KW - Chromosomes, Human, Pair 5 KW - Cloning, Molecular KW - Base Sequence KW - Transfection KW - Molecular Sequence Data KW - DNA, Complementary -- chemistry KW - Aging -- genetics KW - Cyclins -- chemistry KW - Cyclins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69710911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene&rft.atitle=Gene+structure+and+chromosomal+localization+of+mouse+cyclin+G2+%28Ccng2%29.&rft.au=Jensen%2C+M+R%3BAudolfsson%2C+T%3BKeck%2C+C+L%3BZimonjic%2C+D+B%3BThorgeirsson%2C+S+S&rft.aulast=Jensen&rft.aufirst=M&rft.date=1999-04-16&rft.volume=230&rft.issue=2&rft.spage=171&rft.isbn=&rft.btitle=&rft.title=Gene&rft.issn=03781119&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF079877; GENBANK; AF005885 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha. AN - 69705463; 10213494 AB - Estrogens have important functions in mammary gland development and carcinogenesis. To better define these roles, we have used two previously characterized lines of genetically altered mice: estrogen receptor-alpha (ER alpha) knockout (ERKO) mice, which lack the gene encoding ER alpha, and mouse mammary virus tumor (MMTV)-Wnt-1 transgenic mice (Wnt-1 TG), which develop mammary hyperplasia and neoplasia due to ectopic production of the Wnt-1 secretory glycoprotein. We have crossed these lines to ascertain the effects of ER alpha deficiency on mammary gland development and carcinogenesis in mice expressing the Wnt-1 transgene. Introduction of the Wnt-1 transgene into the ERKO background stimulates proliferation of alveolar-like epithelium, indicating that Wnt-1 protein can promote mitogenesis in the absence of an ER alpha-mediated response. The hyperplastic glandular tissue remains confined to the nipple region, implying that the requirement for ER alpha in ductal expansion is not overcome by ectopic Wnt-1. Tumors were detected in virgin ERKO females expressing the Wnt-1 transgene at an average age (48 weeks) that is twice that seen in virgin Wnt-1 TG mice (24 weeks) competent to produce ER alpha. Prepubertal ovariectomy of Wnt-1 TG mice also extended tumor latency to 42 weeks. However, pregnancy did not appear to accelerate the appearance of tumors in Wnt-1 TG mice, and tumor growth rates were not measurably affected by late ovariectomy. Small hyperplastic mammary glands were observed in Wnt-1 TG males, regardless of ER alpha gene status; the glands were similar in appearance to those found in ERKO/Wnt-1 TG females. Mammary tumors also occurred in Wnt-1 TG males; latency tended to be longer in the heterozygous ER alpha and ERKO males (86 to 100 weeks) than in wild-type ER alpha mice (ca. 75 weeks). We conclude that ectopic expression of the Wnt-1 proto-oncogene can induce mammary hyperplasia and tumorigenesis in the absence of ER alpha in female and male mice. The delayed time of tumor appearance may depend on the number of cells at risk of secondary events in the hyperplastic glands, on the carcinogenesis-promoting effects of ER alpha signaling, or on both. JF - Cancer research AU - Bocchinfuso, W P AU - Hively, W P AU - Couse, J F AU - Varmus, H E AU - Korach, K S AD - Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 1869 EP - 1876 VL - 59 IS - 8 SN - 0008-5472, 0008-5472 KW - Estrogen Receptor alpha KW - 0 KW - Estrogens KW - Proto-Oncogene Proteins KW - Receptors, Estrogen KW - Wnt Proteins KW - Wnt1 Protein KW - Wnt1 protein, mouse KW - Zebrafish Proteins KW - Index Medicus KW - Animals KW - Estrogens -- metabolism KW - Gene Transfer Techniques KW - Mice KW - Receptors, Estrogen -- metabolism KW - Gene Deletion KW - Mice, Knockout KW - Hyperplasia KW - Receptors, Estrogen -- genetics KW - Transformation, Genetic KW - Cell Transformation, Viral KW - Female KW - Male KW - Proto-Oncogene Proteins -- biosynthesis KW - Mammary Neoplasms, Animal -- pathology KW - Mammary Neoplasms, Animal -- genetics KW - Breast -- pathology KW - Proto-Oncogene Proteins -- genetics KW - Mammary Tumor Virus, Mouse -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69705463?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=A+mouse+mammary+tumor+virus-Wnt-1+transgene+induces+mammary+gland+hyperplasia+and+tumorigenesis+in+mice+lacking+estrogen+receptor-alpha.&rft.au=Bocchinfuso%2C+W+P%3BHively%2C+W+P%3BCouse%2C+J+F%3BVarmus%2C+H+E%3BKorach%2C+K+S&rft.aulast=Bocchinfuso&rft.aufirst=W&rft.date=1999-04-15&rft.volume=59&rft.issue=8&rft.spage=1869&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-07 N1 - Date created - 1999-06-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Power and sample size calculations in case-control studies of gene-environment interactions: comments on different approaches. AN - 69699445; 10206617 AB - Power and sample size considerations are critical for the design of epidemiologic studies of gene-environment interactions. Hwang et al. (Am J Epidemiol 1994;140:1029-37) and Foppa and Spiegelman (Am J Epidemiol 1997;146:596-604) have presented power and sample size calculations for case-control studies of gene-environment interactions. Comparisons of calculations using these approaches and an approach for general multivariate regression models for the odds ratio previously published by Lubin and Gail (Am J Epidemiol 1990; 131:552-66) have revealed substantial differences under some scenarios. These differences are the result of a highly restrictive characterization of the null hypothesis in Hwang et al. and Foppa and Spiegelman, which results in an underestimation of sample size and overestimation of power for the test of a gene-environment interaction. A computer program to perform sample size and power calculations to detect additive or multiplicative models of gene-environment interactions using the Lubin and Gail approach will be available free of charge in the near future from the National Cancer Institute. JF - American journal of epidemiology AU - García-Closas, M AU - Lubin, J H AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 689 EP - 692 VL - 149 IS - 8 SN - 0002-9262, 0002-9262 KW - Index Medicus KW - Causality KW - Software KW - Models, Genetic KW - Humans KW - Case-Control Studies KW - Models, Statistical KW - Sample Size KW - Risk Assessment KW - Genetic Predisposition to Disease -- genetics KW - Environmental Exposure -- statistics & numerical data KW - Environmental Exposure -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69699445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+epidemiology&rft.atitle=Power+and+sample+size+calculations+in+case-control+studies+of+gene-environment+interactions%3A+comments+on+different+approaches.&rft.au=Garc%C3%ADa-Closas%2C+M%3BLubin%2C+J+H&rft.aulast=Garc%C3%ADa-Closas&rft.aufirst=M&rft.date=1999-04-15&rft.volume=149&rft.issue=8&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=American+journal+of+epidemiology&rft.issn=00029262&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-26 N1 - Date created - 1999-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Am J Epidemiol. 1997 Oct 1;146(7):596-604 [9326439] Am J Epidemiol. 1994 Dec 1;140(11):1029-37 [7985651] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells. AN - 69692837; 10202031 AB - In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with phosphatidylinositol 3-kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase inhibitor), and wortmannin (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS-2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation of PDE4 by IL-3. These results suggested that IL-4-induced activation of PDE3 and PDE4 was downstream of IRS-2/PI3-K, not STAT6, and that inhibition of tyrosine phosphorylation of IRS molecules might be one mechnism whereby TNF-alpha could selectively regulate activities of cytokines that utilized IRS proteins as signal transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen-activated protein (MAP) kinase and protein kinase B via PI3-K signals; PMA activated only MAP kinase via PKC signals. The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL-3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced activation of PDE3. In FDCP2 cells transfected with constitutively activated MEK, MAP kinase and PDE4, not PDE3, were activated. Thus, in FDCP2 cells, PDE4 can be activated by overlapping MAP kinase-dependent pathways involving PI3-K (IL-4, IL-3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-2/PI3-K dependent). JF - Journal of immunology (Baltimore, Md. : 1950) AU - Ahmad, F AU - Gao, G AU - Wang, L M AU - Landstrom, T R AU - Degerman, E AU - Pierce, J H AU - Manganiello, V C AD - Pulmonary/Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 4864 EP - 4875 VL - 162 IS - 8 SN - 0022-1767, 0022-1767 KW - Androstadienes KW - 0 KW - Insulin Receptor Substrate Proteins KW - Interleukin-3 KW - Intracellular Signaling Peptides and Proteins KW - Irs2 protein, mouse KW - Phosphoproteins KW - Proto-Oncogene Proteins KW - STAT6 Transcription Factor KW - Stat6 protein, mouse KW - Trans-Activators KW - Tumor Necrosis Factor-alpha KW - Tyrphostins KW - alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide KW - Interleukin-4 KW - 207137-56-2 KW - Tyrosine KW - 42HK56048U KW - Granulocyte-Macrophage Colony-Stimulating Factor KW - 83869-56-1 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Receptor, Insulin KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - Proto-Oncogene Proteins c-akt KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - 3',5'-Cyclic-AMP Phosphodiesterases KW - EC 3.1.4.17 KW - Cyclic Nucleotide Phosphodiesterases, Type 3 KW - Cyclic Nucleotide Phosphodiesterases, Type 4 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - wortmannin KW - XVA4O219QW KW - Abridged Index Medicus KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Biological Transport KW - Proto-Oncogene Proteins -- metabolism KW - Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology KW - Tumor Cells, Cultured KW - Phosphorylation KW - Enzyme Activation -- drug effects KW - Signal Transduction -- immunology KW - Tyrosine -- metabolism KW - Tyrphostins -- pharmacology KW - Time Factors KW - Phosphoproteins -- metabolism KW - Receptor, Insulin -- metabolism KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Androstadienes -- pharmacology KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Enzyme Activation -- immunology KW - Cell Line KW - Interleukin-3 -- pharmacology KW - Interleukin-4 -- pharmacology KW - Hematopoietic Stem Cells -- enzymology KW - 3',5'-Cyclic-AMP Phosphodiesterases -- metabolism KW - Hematopoietic Stem Cells -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69692837?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=IL-3+and+IL-4+activate+cyclic+nucleotide+phosphodiesterases+3+%28PDE3%29+and+4+%28PDE4%29+by+different+mechanisms+in+FDCP2+myeloid+cells.&rft.au=Ahmad%2C+F%3BGao%2C+G%3BWang%2C+L+M%3BLandstrom%2C+T+R%3BDegerman%2C+E%3BPierce%2C+J+H%3BManganiello%2C+V+C&rft.aulast=Ahmad&rft.aufirst=F&rft.date=1999-04-15&rft.volume=162&rft.issue=8&rft.spage=4864&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Toxicity of 3,3',4,4'-tetrachloroazobenzene in rats and mice. AN - 69685682; 10198280 AB - The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in both males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point. Copyright 1999 Academic Press. JF - Toxicology and applied pharmacology AU - van Birgelen, A P AU - Hébert, C D AU - Wenk, M L AU - Grimes, L K AU - Chapin, R E AU - Mahler, J AU - Travlos, G S AU - Bucher, J R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA. VANBIRGE@NIEHS.NIH.GOV Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 147 EP - 159 VL - 156 IS - 2 SN - 0041-008X, 0041-008X KW - Azo Compounds KW - 0 KW - Chlorobenzenes KW - Thyroid Hormones KW - 3,4,3',4'-tetrachloroazobenzene KW - 14047-09-7 KW - Index Medicus KW - Animals KW - Mice KW - Estrus -- drug effects KW - Blood Cell Count KW - Rats KW - Mice, Inbred Strains KW - Rats, Inbred F344 KW - Spermatozoa -- drug effects KW - Body Weight -- drug effects KW - Thyroid Hormones -- blood KW - Species Specificity KW - Female KW - Male KW - Spermatozoa -- ultrastructure KW - Organ Size -- drug effects KW - Chlorobenzenes -- toxicity KW - Azo Compounds -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69685682?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Toxicity+of+3%2C3%27%2C4%2C4%27-tetrachloroazobenzene+in+rats+and+mice.&rft.au=van+Birgelen%2C+A+P%3BH%C3%A9bert%2C+C+D%3BWenk%2C+M+L%3BGrimes%2C+L+K%3BChapin%2C+R+E%3BMahler%2C+J%3BTravlos%2C+G+S%3BBucher%2C+J+R&rft.aulast=van+Birgelen&rft.aufirst=A&rft.date=1999-04-15&rft.volume=156&rft.issue=2&rft.spage=147&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-07 N1 - Date created - 1999-05-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interaction of Nickel(II) with histones: in vitro binding of nickel(II) to the core histone tetramer. AN - 69681734; 10190970 AB - The absorption spectra of Ni(II) bound to the core histone tetramer, (H3-H4)2, of chicken erythrocytes in 500 mM NaCl + 100 mM phosphate (pH 7.4) were recorded. A charge transfer band was seen at 317 nm, characteristic of a bond between Ni(II) and the sulfur atom of Cys-110 of histone H3. The conditional affinity constants for Ni(II) binding at pH 7.4 for low and high Ni(II) saturation (log Kc = 4.26 +/- 0.02 and 5.26 +/- 0.11 M-1, respectively) were calculated from spectrophotometric titrations with the use of this band. The binding of Ni(II) to (H3-H4)2 is proposed to involve the Cys-110 and His-113 of different H3 molecules within the tetramer. The competition between histones and low-molecular-weight chelators for Ni(II) in the cell nucleus, histidine and glutathione, is discussed on the basis of the above results, indicating that histone H3 is very likely to bind Ni(II) dissolved intracellularly from phagocytosed particulate nickel compounds. Copyright 1999 Academic Press. JF - Archives of biochemistry and biophysics AU - Bal, W AU - Karantza, V AU - Moudrianakis, E N AU - Kasprzak, K S AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, FCRDC, Frederick, Maryland, 21702, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 161 EP - 166 VL - 364 IS - 2 SN - 0003-9861, 0003-9861 KW - Histones KW - 0 KW - Polymers KW - Nickel KW - 7OV03QG267 KW - Index Medicus KW - Animals KW - Chickens KW - Binding, Competitive KW - Spectrophotometry, Ultraviolet KW - Histones -- metabolism KW - Polymers -- metabolism KW - Nickel -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69681734?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Interaction+of+Nickel%28II%29+with+histones%3A+in+vitro+binding+of+nickel%28II%29+to+the+core+histone+tetramer.&rft.au=Bal%2C+W%3BKarantza%2C+V%3BMoudrianakis%2C+E+N%3BKasprzak%2C+K+S&rft.aulast=Bal&rft.aufirst=W&rft.date=1999-04-15&rft.volume=364&rft.issue=2&rft.spage=161&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-04 N1 - Date created - 1999-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria. AN - 69677281; 10101204 AB - The mitochondrial theory of aging postulates that organisms age due to the accumulation of DNA damage and mutations in the multiple mitochondrial genomes, leading to mitochondrial dysfunction. Among the wide variety of DNA damage, 8-oxo-deoxyguanosine (8-oxo-dG) has received the most attention due to its mutagenicity and because of the possible correlation between its accumulation and pathological processes like cancer, degenerative diseases and aging. Although still controversial, many studies show that 8-oxo-dG accumulates with age in the mitochondrial (mt) DNA. However, little is known about the processing of this lesion and no study has yet examined whether mtDNA repair changes with age. Here, we report the first study on age-related changes in mtDNA repair, accomplished by assessing the cleavage activity of mitochondrial extracts towards an 8-oxo-dG-containing substrate. In this study, mitochondria obtained from rat heart and liver were used. We find that this enzymatic activity is higher in 12 and 23 month-old rats than in 6 month-old rats, in both liver and heart extracts. These mitochondrial extracts also cleave oligonucleotides containing a U:A mismatch, at the uracil position, reflecting the combined action of mitochondrial uracil DNA glycosylase (mtUDG) and mitochondrial apurinic/apyrimidinic (AP) endonucleases. The mtUDG activity did not change with age in liver mitochondria, but there was a small increase in activity from 6 to 23 months in rat heart extracts, after normalization to citrate synthase activity. Endonuclease G activity, measured by a plasmid relaxation assay, did not show any age-associated change in liver, but there was a significant decrease from 6 to 23 months in heart mitochondria. Our results suggest that the mitochondrial capacity to repair 8-oxo-dG, the main oxidative base damage suggested to accumulate with age in mtDNA, does not decrease, but rather increases with age. The specific increase in 8-oxo-dG endonuclease activity, rather than a general up-regulation of DNA repair in mitochondria, suggests an induction of the 8-oxo-dG-specific repair pathway with age. JF - Nucleic acids research AU - Souza-Pinto, N C AU - Croteau, D L AU - Hudson, E K AU - Hansford, R G AU - Bohr, V A AD - Laboratory of Molecular Genetics, Box 1, National Institute on Aging, National Institutes of Health,5600 Nathan Shock Drive, Baltimore, MD 21224, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 1935 EP - 1942 VL - 27 IS - 8 SN - 0305-1048, 0305-1048 KW - DNA, Mitochondrial KW - 0 KW - 8-oxo-7-hydrodeoxyguanosine KW - 88847-89-6 KW - Deoxyribonuclease IV (Phage T4-Induced) KW - EC 3.1.21.2 KW - DNA Glycosylases KW - EC 3.2.2.- KW - N-Glycosyl Hydrolases KW - Uracil-DNA Glycosidase KW - DNA-Formamidopyrimidine Glycosylase KW - EC 3.2.2.23 KW - Carbon-Oxygen Lyases KW - EC 4.2.- KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - EC 4.2.99.18 KW - Deoxyguanosine KW - G9481N71RO KW - Index Medicus KW - Rats KW - Animals KW - Rats, Wistar KW - Male KW - Aging -- metabolism KW - Mitochondria, Liver -- enzymology KW - DNA Repair KW - Mitochondria, Heart -- enzymology KW - Mitochondria, Heart -- genetics KW - Carbon-Oxygen Lyases -- metabolism KW - Deoxyguanosine -- metabolism KW - N-Glycosyl Hydrolases -- metabolism KW - Mitochondria, Liver -- genetics KW - Aging -- genetics KW - Deoxyguanosine -- analogs & derivatives UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69677281?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nucleic+acids+research&rft.atitle=Age-associated+increase+in+8-oxo-deoxyguanosine+glycosylase%2FAP+lyase+activity+in+rat+mitochondria.&rft.au=Souza-Pinto%2C+N+C%3BCroteau%2C+D+L%3BHudson%2C+E+K%3BHansford%2C+R+G%3BBohr%2C+V+A&rft.aulast=Souza-Pinto&rft.aufirst=N&rft.date=1999-04-15&rft.volume=27&rft.issue=8&rft.spage=1935&rft.isbn=&rft.btitle=&rft.title=Nucleic+acids+research&rft.issn=03051048&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-14 N1 - Date created - 1999-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Murine fibroblast growth factor receptor 1alpha isoforms mediate node regression and are essential for posterior mesoderm development. AN - 69674979; 10191046 AB - Alternative splicing in the fibroblast growth factor receptor 1 (Fgfr1) locus generates a variety of splicing isoforms, including FGFR1alpha isoforms, which contain three immunoglobulin-like loops in the extracellular domain of the receptor. It has been previously shown that embryos carrying targeted disruptions of all major isoforms die during gastrulation, displaying severe growth retardation and defective mesodermal structures. Here we selectively disrupted the FGFR1alpha isoforms and found that they play an essential role in posterior mesoderm formation during gastrulation. We show that the mutant embryos lack caudal somites, develop spina bifida, and die at 9.5-12.5 days of embryonic development because they are unable to establish embryonic circulation. The primary defect is a failure of axial mesoderm cell migration toward the posterior portions of the embryos during gastrulation, as revealed by regional marker analysis and DiI labeling. In contrast, the anterior migration of the notochord is unaffected and the embryonic structures rostral to the forelimb are relatively normal. These data demonstrate that FGF/FGFR1alpha signals are posteriorizing factors that control node regression and posterior embryonic development. Copyright 1999 Academic Press. JF - Developmental biology AU - Xu, X AU - Li, C AU - Takahashi, K AU - Slavkin, H C AU - Shum, L AU - Deng, C X AD - National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA. Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 293 EP - 306 VL - 208 IS - 2 SN - 0012-1606, 0012-1606 KW - Protein Isoforms KW - 0 KW - Receptors, Fibroblast Growth Factor KW - Fgfr1 protein, mouse KW - EC 2.7.10.1 KW - Receptor Protein-Tyrosine Kinases KW - Receptor, Fibroblast Growth Factor, Type 1 KW - Index Medicus KW - Spinal Dysraphism -- genetics KW - Animals KW - Protein Isoforms -- metabolism KW - Spinal Dysraphism -- etiology KW - Mice KW - Protein Isoforms -- deficiency KW - Embryo, Mammalian -- pathology KW - Genotype KW - Mutagenesis, Site-Directed KW - Brain -- abnormalities KW - Abnormalities, Multiple KW - Cell Communication KW - Crosses, Genetic KW - Gastrula KW - Somites KW - Protein Isoforms -- genetics KW - Genes, Lethal KW - Mutation KW - Receptor Protein-Tyrosine Kinases -- deficiency KW - Cell Movement KW - Receptor Protein-Tyrosine Kinases -- genetics KW - Mesoderm -- cytology KW - Mice, Mutant Strains -- embryology KW - Receptors, Fibroblast Growth Factor -- metabolism KW - Receptor Protein-Tyrosine Kinases -- metabolism KW - Receptors, Fibroblast Growth Factor -- deficiency KW - Receptors, Fibroblast Growth Factor -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69674979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Developmental+biology&rft.atitle=Murine+fibroblast+growth+factor+receptor+1alpha+isoforms+mediate+node+regression+and+are+essential+for+posterior+mesoderm+development.&rft.au=Xu%2C+X%3BLi%2C+C%3BTakahashi%2C+K%3BSlavkin%2C+H+C%3BShum%2C+L%3BDeng%2C+C+X&rft.aulast=Xu&rft.aufirst=X&rft.date=1999-04-15&rft.volume=208&rft.issue=2&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Developmental+biology&rft.issn=00121606&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-11 N1 - Date created - 1999-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Binding of SeqA protein to DNA requires interaction between two or more complexes bound to separate hemimethylated GATC sequences AN - 17213313; 4492892 AB - The SeqA protein binds to the post-replicative forms of the origins of replication of the Escherichia coli chromosome (oriC) and the P1 plasmid (P1oriR) at hemimethylated GATC adenine methylation sites. It appears to regulate replication by preventing premature reinitiation. However, SeqA binding is not exclusive to replication origins: different fragments with hemimethylated GATC sites can bind SeqA in vitro when certain rules apply. Most notably, more than one such site must be present on a bound fragment. The protein appears to recognize individual hemimethylated sites, but must undergo an obligate cooperative interaction with a nearby bound protein for stable binding. SeqA contacts both DNA strands in a discrete patch at each hemimethylated GATC sequence. All four GATC bases are contacted and are essential for binding. Although the recognized sequence is symmetrical, the footprint on the methylated strand is always broader, suggesting that the bound protein is positioned asymmetrically with its orientation dictated by the position of the unique methyl group. Studies of alternative spacings and relative orientations of adjacent sites suggest that each site may be recognized by a symmetrical dimer with an induced asymmetry in one of the subunits similar to that seen with certain type II restriction endonucleases. JF - EMBO Journal AU - Brendler, T AU - Austin, S AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA, austin@ncifcrf.gov Y1 - 1999/04/15/ PY - 1999 DA - 1999 Apr 15 SP - 2304 EP - 2310 VL - 18 IS - 8 SN - 0261-4189, 0261-4189 KW - SeqA protein KW - replication origins KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA biosynthesis KW - DNA-binding protein KW - Escherichia coli KW - Methylation KW - Deoxyribonuclease II KW - J 02725:DNA KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17213313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=EMBO+Journal&rft.atitle=Binding+of+SeqA+protein+to+DNA+requires+interaction+between+two+or+more+complexes+bound+to+separate+hemimethylated+GATC+sequences&rft.au=Brendler%2C+T%3BAustin%2C+S&rft.aulast=Brendler&rft.aufirst=T&rft.date=1999-04-15&rft.volume=18&rft.issue=8&rft.spage=2304&rft.isbn=&rft.btitle=&rft.title=EMBO+Journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA biosynthesis; DNA-binding protein; Deoxyribonuclease II; Methylation ER - TY - JOUR T1 - A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein alpha-subunit with impaired receptor-mediated activation because of elevated GTPase activity. AN - 69692583; 10200251 AB - It has been reported that substitution of Arg258, a residue within the GTPase domain of the heterotrimeric guanine nucleotide binding protein (G protein) alpha-subunit (alphas), to alanine (alphas-R258A) results in decreased activation by receptor or aluminum fluoride (AlF4-) and increased basal GDP release. Arg258 interacts with Gln170 in the helical domain, and, presumably, loss of this interaction between the GTPase and helical domain leads to more rapid GDP release, resulting in decreased activation by AlF4- and increased thermolability. In this study, we mutate Gln170 to alanine (alphas-Q170A) and demonstrate that this mutant, like alphas-R258A, has decreased activation by AlF4-, increased thermolability (both reversed in the presence of excess guanine nucleotide), and an increased rate of GDP release. However, unlike alphas-R258A, alphas-Q170A does not have impaired receptor-mediated activation. Therefore, this interdomain interaction is critical to maintain normal guanine nucleotide binding (and hence normal activation by AlF4-) but is not important for receptor-mediated activation. In single turnover GTPase assays, the catalytic rate for GTP hydrolysis of alphas-R258A was 14-fold higher than normal whereas that of alphas-Q170A was unaffected. Examination of the alphas crystal structure suggests that Arg258, through interactions with Glu50, might constrain the position of Arg201, a residue critical for catalyzing the GTPase reaction. This is an example of a mutation in a heterotrimeric G protein that results in an increased intrinsic GTPase activity and provides another mechanism by which G protein mutations can impair signal transduction. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Warner, D R AU - Weinstein, L S AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. dwarner@helix.nih.gov Y1 - 1999/04/13/ PY - 1999 DA - 1999 Apr 13 SP - 4268 EP - 4272 VL - 96 IS - 8 SN - 0027-8424, 0027-8424 KW - Aluminum Compounds KW - 0 KW - Macromolecular Substances KW - Recombinant Proteins KW - Glutamine KW - 0RH81L854J KW - Guanosine Diphosphate KW - 146-91-8 KW - tetrafluoroaluminate KW - 21340-02-3 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Arginine KW - 94ZLA3W45F KW - GTP Phosphohydrolases KW - EC 3.6.1.- KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Adenylyl Cyclases KW - EC 4.6.1.1 KW - Isoproterenol KW - L628TT009W KW - Fluorides KW - Q80VPU408O KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Guanosine Diphosphate -- metabolism KW - Humans KW - Fibrous Dysplasia, Polyostotic -- genetics KW - Adenylyl Cyclases -- metabolism KW - Fluorides -- pharmacology KW - Guanosine 5'-O-(3-Thiotriphosphate) -- pharmacology KW - Isoproterenol -- pharmacology KW - Cloning, Molecular KW - Mutagenesis, Site-Directed KW - Polymerase Chain Reaction KW - Cattle KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Escherichia coli KW - Aluminum Compounds -- pharmacology KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Amino Acid Substitution KW - GTP Phosphohydrolases -- chemistry KW - GTP-Binding Protein alpha Subunits, Gs -- genetics KW - GTP Phosphohydrolases -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69692583?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=A+mutation+in+the+heterotrimeric+stimulatory+guanine+nucleotide+binding+protein+alpha-subunit+with+impaired+receptor-mediated+activation+because+of+elevated+GTPase+activity.&rft.au=Warner%2C+D+R%3BWeinstein%2C+L+S&rft.aulast=Warner&rft.aufirst=D&rft.date=1999-04-13&rft.volume=96&rft.issue=8&rft.spage=4268&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-17 N1 - Date created - 1999-05-17 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1990 Aug 10;249(4969):655-9 [2116665] J Biol Chem. 1989 Sep 15;264(26):15475-82 [2549065] Biochemistry. 1992 Aug 18;31(32):7367-72 [1510926] Endocr Rev. 1992 Aug;13(3):536-65 [1425488] Nature. 1993 Dec 16;366(6456):654-63 [8259210] Biochemistry. 1994 Mar 22;33(11):3237-44 [8136358] Nature. 1994 Jun 23;369(6482):621-8 [8208289] Nature. 1994 Sep 8;371(6493):164-8 [8072545] Science. 1994 Sep 2;265(5177):1405-12 [8073283] Methods Enzymol. 1994;237:146-64 [7934993] Nature. 1989 Aug 31;340(6236):692-6 [2549426] Biochim Biophys Acta. 1990 May 7;1031(2):163-224 [2160274] Methods Enzymol. 1994;237:38-44 [7935012] Cell. 1995 Jan 27;80(2):249-57 [7834744] Science. 1995 Nov 10;270(5238):954-60 [7481799] Cell. 1995 Dec 15;83(6):1047-58 [8521505] Nature. 1996 Apr 18;380(6575):624-7 [8602262] J Biol Chem. 1997 Aug 29;272(35):21673-6 [9268292] Mol Endocrinol. 1997 Oct;11(11):1718-27 [9328353] Science. 1997 Dec 12;278(5345):1943-7 [9395396] J Biol Chem. 1998 Jan 16;273(3):1269-72 [9430654] J Biol Chem. 1998 Jun 12;273(24):15053-60 [9614114] Mol Pharmacol. 1998 Jun;53(6):981-90 [9614199] Nature. 1998 Jul 2;394(6688):35-8 [9665125] J Biol Chem. 1998 Sep 11;273(37):23976-83 [9727013] J Biol Chem. 1999 Feb 19;274(8):4977-84 [9988742] J Biol Chem. 1981 Nov 25;256(22):11517-26 [6271754] J Biol Chem. 1986 Jun 5;261(16):7393-9 [3086311] Science. 1987 Nov 27;238(4831):1288-92 [2446390] Proc Natl Acad Sci U S A. 1988 Apr;85(7):2081-5 [3127824] Nature. 1988 Aug 25;334(6184):712-5 [3137475] FEBS Lett. 1989 Jun 5;249(2):189-94 [2500363] N Engl J Med. 1991 Dec 12;325(24):1688-95 [1944469] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Tissue inhibitor of metalloproteinases-1 (TIMP-1) binds to the cell surface and translocates to the nucleus of human MCF-7 breast carcinoma cells. AN - 69687934; 10198240 AB - To study cellular and subcellular localization of TIMP-1, we constructed a cDNA which would express a chimeric protein, TIMP-1-EGFP, having the enhanced green fluorescent protein of the jelly fish Aequorea victoria fused to the carboxyl-terminus of TIMP-1. Chinese Hamster Ovary (CHO) cells were stably transfected with the TIMP-1-EGFP expressing plasmid. The secreted chimera was processed through the endoplasmic reticulum and Golgi, as was shown by fluorescent confocal microscopy after incubations at temperatures which block processing at the intermediate compartment and the trans-Golgi network. In a co-culture system, secreted TIMP-1-EGFP could be visualized binding to the surface of MCF-7 breast carcinoma cells but not non-neoplastic HBL-100 breast epithelial cells. TIMP-1-EGFP localized to the nucleus of MCF-7 cells after 72 hrs in co-culture. These findings suggest that TIMP-1 may preferentially bind to and be taken up by malignant breast epithelial cells and that TIMP-1 may play a yet unidentified role in nuclear functions. Copyright 1999 Academic Press. JF - Biochemical and biophysical research communications AU - Ritter, L M AU - Garfield, S H AU - Thorgeirsson, U P AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland, 20892, USA. Y1 - 1999/04/13/ PY - 1999 DA - 1999 Apr 13 SP - 494 EP - 499 VL - 257 IS - 2 SN - 0006-291X, 0006-291X KW - Luminescent Proteins KW - 0 KW - Protein Sorting Signals KW - Recombinant Fusion Proteins KW - Tissue Inhibitor of Metalloproteinase-1 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Index Medicus KW - Microscopy, Confocal KW - Coculture Techniques KW - Animals KW - Protein Sorting Signals -- genetics KW - Humans KW - Luminescent Proteins -- secretion KW - Molecular Weight KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Tumor Cells, Cultured KW - Breast -- cytology KW - Molecular Sequence Data KW - Recombinant Fusion Proteins -- genetics KW - CHO Cells KW - Golgi Apparatus -- metabolism KW - Endoplasmic Reticulum -- secretion KW - Endoplasmic Reticulum -- metabolism KW - Temperature KW - Recombinant Fusion Proteins -- secretion KW - Amino Acid Sequence KW - Luminescent Proteins -- metabolism KW - Luminescent Proteins -- chemistry KW - Golgi Apparatus -- secretion KW - Epithelial Cells KW - Transfection KW - Luminescent Proteins -- genetics KW - Cricetinae KW - Tissue Inhibitor of Metalloproteinase-1 -- chemistry KW - Breast Neoplasms -- pathology KW - Cell Nucleus -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- metabolism KW - Breast Neoplasms -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- secretion KW - Cell Membrane -- metabolism KW - Tissue Inhibitor of Metalloproteinase-1 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69687934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Tissue+inhibitor+of+metalloproteinases-1+%28TIMP-1%29+binds+to+the+cell+surface+and+translocates+to+the+nucleus+of+human+MCF-7+breast+carcinoma+cells.&rft.au=Ritter%2C+L+M%3BGarfield%2C+S+H%3BThorgeirsson%2C+U+P&rft.aulast=Ritter&rft.aufirst=L&rft.date=1999-04-13&rft.volume=257&rft.issue=2&rft.spage=494&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-24 N1 - Date created - 1999-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interferon-gamma, bacterial lipopolysaccharide, and tumor necrosis factor-alpha induce CD11a mRNA and protein via Na+/H+ exchange and protein kinase C-dependent mechanisms in tissue macrophages. AN - 69687447; 10198263 AB - Previously CD11a or leukocyte function-associated antigen alpha-1 was found to be induced at the surface protein level in thioglycolate-elicited peritoneal macrophages by bacterial lipopolysaccharide and interferon-gamma. To investigate this induction further, Northern blotting and enzyme-linked immunosorbent assays were used to examine the role of second messengers in CD11a gene product induction by these agents. Here I report that CD11a RNA and cell surface protein induced by bacterial lipopolysaccharide and tumor necrosis factor-alpha are sensitive to inhibition of protein kinase C, while insensitive to inhibition of Na+/H+ exchange. CD11a induction by interferon-gamma conversely is sensitive to inhibition of Na+/H+ exchange and insensitive to inhibition of protein kinase C. These observations indicate that CD11a may be induced by multiple and separate second messenger systems in primary macrophages. Copyright 1999 Academic Press. JF - Biochemical and biophysical research communications AU - Shackelford, R E AD - Department of Pathology, Duke University Medical Center, Durham, North Carolina, 27709, USA. shackel1@niehs.nih.gov Y1 - 1999/04/13/ PY - 1999 DA - 1999 Apr 13 SP - 635 EP - 641 VL - 257 IS - 2 SN - 0006-291X, 0006-291X KW - Lipopolysaccharides KW - 0 KW - Lymphocyte Function-Associated Antigen-1 KW - RNA, Messenger KW - Receptors, IgG KW - Sodium-Hydrogen Antiporter KW - Thioglycolates KW - Tumor Necrosis Factor-alpha KW - Amiloride KW - 7DZO8EB0Z3 KW - Interferon-gamma KW - 82115-62-6 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Staurosporine KW - H88EPA0A3N KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Animals KW - Cell Membrane -- drug effects KW - Dose-Response Relationship, Drug KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Transcriptional Activation -- drug effects KW - Mice KW - Amiloride -- pharmacology KW - Amiloride -- analogs & derivatives KW - Staurosporine -- pharmacology KW - RNA, Messenger -- metabolism KW - Cells, Cultured KW - Second Messenger Systems -- drug effects KW - Mice, Inbred C57BL KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Membrane -- metabolism KW - Thioglycolates -- pharmacology KW - Time Factors KW - Receptors, IgG -- genetics KW - Protein Kinase C -- metabolism KW - Lymphocyte Function-Associated Antigen-1 -- genetics KW - Interferon-gamma -- antagonists & inhibitors KW - Protein Kinase C -- antagonists & inhibitors KW - Lymphocyte Function-Associated Antigen-1 -- metabolism KW - Sodium-Hydrogen Antiporter -- metabolism KW - Lipopolysaccharides -- pharmacology KW - Macrophages, Peritoneal -- metabolism KW - Interferon-gamma -- pharmacology KW - Sodium-Hydrogen Antiporter -- antagonists & inhibitors KW - Macrophages, Peritoneal -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69687447?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Interferon-gamma%2C+bacterial+lipopolysaccharide%2C+and+tumor+necrosis+factor-alpha+induce+CD11a+mRNA+and+protein+via+Na%2B%2FH%2B+exchange+and+protein+kinase+C-dependent+mechanisms+in+tissue+macrophages.&rft.au=Shackelford%2C+R+E&rft.aulast=Shackelford&rft.aufirst=R&rft.date=1999-04-13&rft.volume=257&rft.issue=2&rft.spage=635&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-24 N1 - Date created - 1999-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Universal conservation in translation initiation revealed by human and archaeal homologs of bacterial translation initiation factor IF2 AN - 17215309; 4493167 AB - Binding of initiator methionyl-tRNA to ribosomes is catalyzed in prokaryotes by initiation factor (IF) IF2 and in eukaryotes by eIF2. The discovery of both IF2 and eIF2 homologs in yeast and archaea suggested that these microbes possess an evolutionarily intermediate protein synthesis apparatus. We describe the identification of a human IF2 homolog, and we demonstrate by using in vivo and in vitro assays that human IF2 functions as a translation factor. In addition, we show that archaea IF2 can substitute for its yeast homolog both in vivo and in vitro. We propose a universally conserved function for IF2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site. JF - Proceedings of the National Academy of Sciences, USA AU - Lee, J H AU - Choi, S K AU - Roll-Mecak, A AU - Burley, S K AU - Dever, TE AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health Bethesda, MD 20892-2716, tdever@box-t.nih.gov Y1 - 1999/04/13/ PY - 1999 DA - 1999 Apr 13 SP - 4342 EP - 4347 VL - 96 IS - 08 SN - 0027-8424, 0027-8424 KW - initiation factor IF2 KW - man KW - nucleotide sequence KW - tRNA Met KW - yeast KW - yeasts KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Archaea KW - Translation initiation KW - Initiation factor eIF-2 KW - J 02726:RNA and ribosomes KW - N 14430:Translation initiation, elongation & termination UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17215309?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Universal+conservation+in+translation+initiation+revealed+by+human+and+archaeal+homologs+of+bacterial+translation+initiation+factor+IF2&rft.au=Lee%2C+J+H%3BChoi%2C+S+K%3BRoll-Mecak%2C+A%3BBurley%2C+S+K%3BDever%2C+TE&rft.aulast=Lee&rft.aufirst=J&rft.date=1999-04-13&rft.volume=96&rft.issue=08&rft.spage=4342&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Archaea; Translation initiation; Initiation factor eIF-2 ER - TY - JOUR T1 - Apoptosis Induced by Pseudomonas Exotoxin: A Sensitive and Rapid Marker for Gene Delivery in Vivo AN - 17352336; 4510479 AB - The rapid progress in gene therapy has expanded our ability to alter genetic structure, necessitating the development of methods for detecting the activity of new vectors. The central concept of a reporter gene is simple: it is a defined nucleotide sequence, which when introduced into a biological system, yields a readily measurable phenotype on expression. This provides a convenient parameter that is correlated to the molecular events associated with genetic expression. In this study we demonstrate that Pseudomonas exotoxin A (PE) can serve as a sensitive reporter gene to detect gene expression in single cells of mouse lung on cationic liposome delivery of PE-encoding DNA in vivo. Furthermore, we show that PE expression can be detected as early as 2 hr after systemic gene delivery in lungs of recipient mice. We compared PE with the widely used beta -galactosidase gene for this purpose. PE induces apoptosis that can be detected by TdT end labeling of DNA fragments (TUNEL assay) Since few expressed PE molecules are necessary to trigger the apoptosis cascade, the minimal amount of PE-encoding plasmid DNA needed for detection of apoptotic cells after systemic delivery was 0.1 mu g per animal compared with at least 1 mu g for the beta -galactosidase-encoding plasmid DNA. The maximum number of apoptotic cells detected in lungs was about 15-20 times higher than the maximum number of beta -galactosidase-positive cells. Specificity of apoptosis due to PE expression on delivery of the PE-encoding plasmid was shown by prevention of the apoptotic cascade by the caspase inhibitor Z-VAD-fmk. JF - Human Gene Therapy AU - Hafkemeyer, P AU - Brinkmann, U AU - Gottesman, M M AU - Pastan, I AD - National Cancer Institute, National Institutes of Health, Building 37, Room 4E16, 37 Convent Drive, MSC-4255, Bethesda, MD 20892-4255, USA Y1 - 1999/04/10/ PY - 1999 DA - 1999 Apr 10 SP - 923 EP - 934 VL - 10 IS - 6 SN - 1043-0342, 1043-0342 KW - Pseudomonas KW - exotoxin A KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Expression vectors KW - Gene therapy KW - Reporter gene KW - Plasmids KW - Exotoxins KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17352336?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Apoptosis+Induced+by+Pseudomonas+Exotoxin%3A+A+Sensitive+and+Rapid+Marker+for+Gene+Delivery+in+Vivo&rft.au=Hafkemeyer%2C+P%3BBrinkmann%2C+U%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Hafkemeyer&rft.aufirst=P&rft.date=1999-04-10&rft.volume=10&rft.issue=6&rft.spage=923&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018328 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Plasmids; Gene therapy; Exotoxins; Reporter gene; Expression vectors DO - http://dx.doi.org/10.1089/10430349950018328 ER - TY - JOUR T1 - Augmentation of Melanoma-Specific Gene Expression Using a Tandem Melanocyte-Specific Enhancer Results in Increased Cytotoxicity of the Purine Nucleoside Phosphorylase Gene in Melanoma AN - 17287249; 4510476 AB - The lineage-specific human tyrosinase promoter has been used to successfully target gene expression at the transcriptional level to melanoma cells. The tyrosinase promoter, alone and in combination with a single, or a dual, tandem melanocyte-specific enhancer, was used to regulate expression of the firefly luciferase reporter gene. Transient transfections of these tissue-specific luciferase constructs in human and murine melanoma (Pmel, B16mel) and colon carcinoma (WiDr, MC38) cell lines resulted in melanoma-specific luciferase expression that was amplified 5- and 500-fold with the addition of a single or double enhancer, respectively, to the tyrosinase promoter. When the double enhancer-promoter construct expressed the highly toxic Escherichia coli purine nucleoside phosphorylase (PNP) gene, transfection of the same cell lines followed by administration of the prodrug 6-methyl purine deoxyriboside (6-MPDR) at a concentration of 50 mu M caused melanoma-specific in vitro cell killing. Within 5 days after prodrug administration methylthiazol-tetrazolium (MTT) cytotoxicity assays showed that only 15 and 9% of Pmel and B16mel cells, respectively, remained viable compared with controls. This effect was highly specific, as 90 and 96% of WiDr and MC38 colon carcinoma cells remained viable 5 days after identical treatment. This effect was a direct result of increased tissue-specific conversion of 6-MPDR to the toxic metabolite 6-methylpurine (6-MP), as documented by HPLC analysis of culture supernatants. These results show that the dual tandem melanocyte-specific enhancer provides powerful amplification of the transcriptional targeting of gene expression afforded by use of the tyrosinase promoter. This amplification translates into increased, highly specific cytotoxicity to melanoma by the PNP/6-MPDR enzyme/prodrug system and, therefore, has potential efficacy in the use of gene therapy for the treatment of metastatic melanoma. JF - Human Gene Therapy AU - Park, B J AU - Brown, C K AU - Hu, Yun AU - Alexander, H R AU - Horti, J AU - Raje, S AU - Figg, W D AU - Bartlett, D L AD - Metabolism Section, Surgery Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 2B16, Bethesda, MD 20892, USA, David_Bartlett@nih.gov Y1 - 1999/04/10/ PY - 1999 DA - 1999 Apr 10 SP - 889 EP - 898 VL - 10 IS - 6 SN - 1043-0342, 1043-0342 KW - 6-methyl purine deoxyribosides KW - 6-methylpurine KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Purine-nucleoside phosphorylase KW - Gene therapy KW - Monophenol monooxygenase KW - Melanoma KW - Promoters KW - Cytotoxicity KW - Gene regulation KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17287249?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Augmentation+of+Melanoma-Specific+Gene+Expression+Using+a+Tandem+Melanocyte-Specific+Enhancer+Results+in+Increased+Cytotoxicity+of+the+Purine+Nucleoside+Phosphorylase+Gene+in+Melanoma&rft.au=Park%2C+B+J%3BBrown%2C+C+K%3BHu%2C+Yun%3BAlexander%2C+H+R%3BHorti%2C+J%3BRaje%2C+S%3BFigg%2C+W+D%3BBartlett%2C+D+L&rft.aulast=Park&rft.aufirst=B&rft.date=1999-04-10&rft.volume=10&rft.issue=6&rft.spage=889&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018292 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Purine-nucleoside phosphorylase; Melanoma; Gene therapy; Cytotoxicity; Promoters; Gene regulation; Monophenol monooxygenase DO - http://dx.doi.org/10.1089/10430349950018292 ER - TY - JOUR T1 - DNA immunization of mice and macaques with plasmids encoding hepatitis C virus envelope E2 protein expressed intracellularly and on the cell surface AN - 17289943; 4506099 AB - We analyzed the humoral immune response elicited by hepatitis C virus (HCV) E2 protein expressed in vivo after injection of plasmid DNA into mice and rhesus macaques. Three plasmids were used for immunization: a plasmid containing the entire sequence of the E2 and p7 genes (pE2); a plasmid encoding a truncated form of the E2 protein targeted to the cell surface (pE2surf); a control plasmid (pDisplay) lacking an HCV insert. Each plasmid was injected intramuscularly into 5 mice and intraepidermally (via gene gun) into 5 mice. Immunization was repeated three times at three week intervals. Five macaques were injected intramuscularly (two with pE2, two with pE2surf and one with pDisplay) and immunization was repeated after 8 weeks. All mice immunized via gene gun with pE2 or pE2surf developed anti-E2. The animals immunized with pE2surf developed an earlier and stronger humoral immune response than those immunized with pE2. Only 2 of the mice injected by the intramuscular route, both immunized with pE2surf, developed detectable anti-E2. One of the two macaques immunized with pE2 and both macaques immunized with pE2surf developed anti-E2; the humoral immune response was much stronger in the animals immunized with pE2surf. Our results suggest that presentation of HCV E2 on the cell surface may increase its immunogenicity while preserving its ability to react with antibodies generated during a natural infection. JF - Vaccine AU - Forns, X AU - Emerson, SU AU - Tobin, G J AU - Mushahwar, I K AU - Purcell, R H AU - Bukh, J AD - Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 7, Room 201, 7 Center Dr MSC 0740, Bethesda, MD 20892-0740, USA Y1 - 1999/04/09/ PY - 1999 DA - 1999 Apr 09 SP - 1992 EP - 2002 VL - 17 IS - 15-16 SN - 0264-410X, 0264-410X KW - DNA vaccines KW - Macaca mulatta KW - Macaques KW - double prime E2 protein KW - hepatitis C virus KW - immunology KW - mice KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Envelopes KW - Immune response (humoral) KW - Macaca KW - Plasmids KW - Hepatitis C virus KW - Immunogenicity KW - DNA KW - Vaccines KW - F 06807:Active immunization KW - V 22150:Animal models & experimentally-induced viral infections KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17289943?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=DNA+immunization+of+mice+and+macaques+with+plasmids+encoding+hepatitis+C+virus+envelope+E2+protein+expressed+intracellularly+and+on+the+cell+surface&rft.au=Forns%2C+X%3BEmerson%2C+SU%3BTobin%2C+G+J%3BMushahwar%2C+I+K%3BPurcell%2C+R+H%3BBukh%2C+J&rft.aulast=Forns&rft.aufirst=X&rft.date=1999-04-09&rft.volume=17&rft.issue=15-16&rft.spage=1992&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Hepatitis C virus; Macaca; Plasmids; Immune response (humoral); DNA; Vaccines; Immunogenicity; Envelopes ER - TY - JOUR T1 - Novel mutations of the MET proto-oncogene in papillary renal carcinomas. AN - 69752515; 10327054 AB - Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene. These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase. The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma. JF - Oncogene AU - Schmidt, L AU - Junker, K AU - Nakaigawa, N AU - Kinjerski, T AU - Weirich, G AU - Miller, M AU - Lubensky, I AU - Neumann, H P AU - Brauch, H AU - Decker, J AU - Vocke, C AU - Brown, J A AU - Jenkins, R AU - Richard, S AU - Bergerheim, U AU - Gerrard, B AU - Dean, M AU - Linehan, W M AU - Zbar, B AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1999/04/08/ PY - 1999 DA - 1999 Apr 08 SP - 2343 EP - 2350 VL - 18 IS - 14 SN - 0950-9232, 0950-9232 KW - Codon KW - 0 KW - DNA, Neoplasm KW - Neoplasm Proteins KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - Proto-Oncogene Proteins c-met KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Codon -- genetics KW - Models, Molecular KW - DNA Mutational Analysis KW - Humans KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Adenoma -- metabolism KW - Sequence Alignment KW - Phosphorylation KW - Neoplastic Syndromes, Hereditary -- genetics KW - Transfection KW - Protein Processing, Post-Translational -- genetics KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - 3T3 Cells -- metabolism KW - Sequence Homology, Amino Acid KW - Adenoma -- genetics KW - Cell Transformation, Neoplastic -- genetics KW - Protein Conformation KW - Kidney Neoplasms -- genetics KW - Proto-Oncogene Proteins c-met -- genetics KW - Proto-Oncogene Proteins c-met -- chemistry KW - Proto-Oncogene Proteins c-met -- metabolism KW - Neoplasm Proteins -- genetics KW - Point Mutation KW - DNA, Neoplasm -- genetics KW - Neoplasm Proteins -- chemistry KW - Proto-Oncogenes KW - Neoplasm Proteins -- metabolism KW - Carcinoma, Papillary -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69752515?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Novel+mutations+of+the+MET+proto-oncogene+in+papillary+renal+carcinomas.&rft.au=Schmidt%2C+L%3BJunker%2C+K%3BNakaigawa%2C+N%3BKinjerski%2C+T%3BWeirich%2C+G%3BMiller%2C+M%3BLubensky%2C+I%3BNeumann%2C+H+P%3BBrauch%2C+H%3BDecker%2C+J%3BVocke%2C+C%3BBrown%2C+J+A%3BJenkins%2C+R%3BRichard%2C+S%3BBergerheim%2C+U%3BGerrard%2C+B%3BDean%2C+M%3BLinehan%2C+W+M%3BZbar%2C+B&rft.aulast=Schmidt&rft.aufirst=L&rft.date=1999-04-08&rft.volume=18&rft.issue=14&rft.spage=2343&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-03 N1 - Date created - 1999-06-03 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1IRK; PDB N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of substrate binding site of cyclin-dependent kinase 5. AN - 69652538; 10092646 AB - Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine. Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown. We have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5. The experimental data and computer simulations suggest that Asp86 and Asp91 are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates. JF - The Journal of biological chemistry AU - Sharma, P AU - Steinbach, P J AU - Sharma, M AU - Amin, N D AU - Barchi, J J AU - Pant, H C AD - Laboratory of Neurochemistry NINDS, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04/02/ PY - 1999 DA - 1999 Apr 02 SP - 9600 EP - 9606 VL - 274 IS - 14 SN - 0021-9258, 0021-9258 KW - Asparagine KW - 7006-34-0 KW - Cyclin-Dependent Kinase 5 KW - EC 2.7.11.1 KW - Protein-Serine-Threonine Kinases KW - CDC2-CDC28 Kinases KW - EC 2.7.11.22 KW - Cyclin-Dependent Kinase 2 KW - Cyclin-Dependent Kinases KW - Index Medicus KW - Protein-Serine-Threonine Kinases -- chemistry KW - Computer Simulation KW - Asparagine -- metabolism KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Kinetics KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Conformation KW - Cyclin-Dependent Kinases -- metabolism KW - Cyclin-Dependent Kinases -- genetics KW - Cyclin-Dependent Kinases -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69652538?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Identification+of+substrate+binding+site+of+cyclin-dependent+kinase+5.&rft.au=Sharma%2C+P%3BSteinbach%2C+P+J%3BSharma%2C+M%3BAmin%2C+N+D%3BBarchi%2C+J+J%3BPant%2C+H+C&rft.aulast=Sharma&rft.aufirst=P&rft.date=1999-04-02&rft.volume=274&rft.issue=14&rft.spage=9600&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-27 N1 - Date created - 1999-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo. AN - 69651475; 10092649 AB - Niemann-Pick C disease (NP-C) is a neurovisceral lysosomal storage disorder. A variety of studies have highlighted defective sterol trafficking from lysosomes in NP-C cells. However, the heterogeneous nature of additional accumulating metabolites suggests that the cellular lesion may involve a more generalized block in retrograde lysosomal trafficking. Immunocytochemical studies in fibroblasts reveal that the NPC1 gene product resides in a novel set of lysosome-associated membrane protein-2 (LAMP2)(+)/mannose 6-phosphate receptor(-) vesicles that can be distinguished from cholesterol-enriched LAMP2(+) lysosomes. Drugs that block sterol transport out of lysosomes also redistribute NPC1 to cholesterol-laden lysosomes. Sterol relocation from lysosomes in cultured human fibroblasts can be blocked at 21 degrees C, consistent with vesicle-mediated transfer. These findings suggest that NPC1(+) vesicles may transiently interact with lysosomes to facilitate sterol relocation. Independent of defective sterol trafficking, NP-C fibroblasts are also deficient in vesicle-mediated clearance of endocytosed [14C]sucrose. Compartmental modeling of the observed [14C]sucrose clearance data targets the trafficking defect caused by mutations in NPC1 to an endocytic compartment proximal to lysosomes. Low density lipoprotein uptake by normal cells retards retrograde transport of [14C]sucrose through this same kinetic compartment, further suggesting that it may contain the sterol-sensing NPC1 protein. We conclude that a distinctive organelle containing NPC1 mediates retrograde lysosomal transport of endocytosed cargo that is not restricted to sterol. JF - The Journal of biological chemistry AU - Neufeld, E B AU - Wastney, M AU - Patel, S AU - Suresh, S AU - Cooney, A M AU - Dwyer, N K AU - Roff, C F AU - Ohno, K AU - Morris, J A AU - Carstea, E D AU - Incardona, J P AU - Strauss, J F AU - Vanier, M T AU - Patterson, M C AU - Brady, R O AU - Pentchev, P G AU - Blanchette-Mackie, E J AD - Lipid Cell Biology Section, Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04/02/ PY - 1999 DA - 1999 Apr 02 SP - 9627 EP - 9635 VL - 274 IS - 14 SN - 0021-9258, 0021-9258 KW - Antibodies KW - 0 KW - Antigens, CD KW - Carrier Proteins KW - LAMP2 protein, human KW - Lysosomal-Associated Membrane Protein 2 KW - Lysosome-Associated Membrane Glycoproteins KW - Membrane Glycoproteins KW - NPC1 protein, human KW - Proteins KW - Receptor, IGF Type 2 KW - Sucrose KW - 57-50-1 KW - Cholesterol KW - 97C5T2UQ7J KW - Index Medicus KW - Humans KW - Biological Transport KW - Receptor, IGF Type 2 -- metabolism KW - Sucrose -- metabolism KW - Amino Acid Sequence KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Endocytosis KW - Cholesterol -- metabolism KW - Cell Compartmentation KW - Antigens, CD -- metabolism KW - Molecular Sequence Data KW - Membrane Glycoproteins -- metabolism KW - Niemann-Pick Diseases -- genetics KW - Niemann-Pick Diseases -- metabolism KW - Lysosomes -- metabolism KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69651475?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=The+Niemann-Pick+C1+protein+resides+in+a+vesicular+compartment+linked+to+retrograde+transport+of+multiple+lysosomal+cargo.&rft.au=Neufeld%2C+E+B%3BWastney%2C+M%3BPatel%2C+S%3BSuresh%2C+S%3BCooney%2C+A+M%3BDwyer%2C+N+K%3BRoff%2C+C+F%3BOhno%2C+K%3BMorris%2C+J+A%3BCarstea%2C+E+D%3BIncardona%2C+J+P%3BStrauss%2C+J+F%3BVanier%2C+M+T%3BPatterson%2C+M+C%3BBrady%2C+R+O%3BPentchev%2C+P+G%3BBlanchette-Mackie%2C+E+J&rft.aulast=Neufeld&rft.aufirst=E&rft.date=1999-04-02&rft.volume=274&rft.issue=14&rft.spage=9627&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-27 N1 - Date created - 1999-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Amyloid beta peptides do not form peptide-derived free radicals spontaneously, but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides. AN - 69649445; 10092619 AB - Amyloid beta (Abeta) peptides play an important role in the pathogenesis of Alzheimer's disease. Free radical generation by Abeta peptides was suggested to be a key mechanism of their neurotoxicity. Reports that neurotoxic free radicals derived from Abeta-(1-40) and Abeta-(25-35) peptides react with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) to form a PBN/.Abeta peptide radical adduct with a specific triplet ESR signal assert that the peptide itself was the source of free radicals. We now report that three Abeta peptides, Abeta-(1-40), Abeta-(25-35), and Abeta-(40-1), do not yield radical adducts with PBN from the Oklahoma Medical Research Foundation (OMRF). In contrast to OMRF PBN, incubation of Sigma PBN in phosphate buffer without Abeta peptides produced a three-line ESR spectrum. It was shown that this nitroxide is di-tert-butylnitroxide and is formed in the Sigma PBN solution as a result of transition metal-catalyzed auto-oxidation of the respective hydroxylamine present as an impurity in the Sigma PBN. Under some conditions, incubation of PBN from Sigma with Abeta-(1-40) or Abeta-(25-35) can stimulate the formation of di-tert-butylnitroxide. It was shown that Abeta peptides enhanced oxidation of cyclic hydroxylamine 1-hydroxy-4-oxo-2,2,6, 6-tetramethylpiperidine (TEMPONE-H), which was strongly inhibited by the treatment of phosphate buffer with Chelex-100. It was shown that ferric and cupric ions are effective oxidants of TEMPONE-H. The data obtained allow us to conclude that under some conditions toxic Abeta peptides Abeta-(1-40) and Abeta-(25-35) enhance metal-catalyzed oxidation of hydroxylamine derivatives, but do not spontaneously form peptide-derived free radicals. JF - The Journal of biological chemistry AU - Dikalov, S I AU - Vitek, M P AU - Maples, K R AU - Mason, R P AD - Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. dikalov@niehs.gov Y1 - 1999/04/02/ PY - 1999 DA - 1999 Apr 02 SP - 9392 EP - 9399 VL - 274 IS - 14 SN - 0021-9258, 0021-9258 KW - Amyloid beta-Peptides KW - 0 KW - Butanes KW - Cyclic N-Oxides KW - Ferric Compounds KW - Free Radicals KW - Hydroxylamines KW - Metals KW - Nitrogen Oxides KW - Piperidines KW - Spin Labels KW - di-t-butyl nitroxide KW - 2406-25-9 KW - 1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidine KW - 3637-11-4 KW - phenyl-N-tert-butylnitrone KW - 3I91332OPG KW - Copper KW - 789U1901C5 KW - Index Medicus KW - Oxidation-Reduction KW - Copper -- metabolism KW - Ferric Compounds -- metabolism KW - Free Radicals -- metabolism KW - Chromatography, High Pressure Liquid KW - Catalysis KW - Amyloid beta-Peptides -- metabolism KW - Nitrogen Oxides -- metabolism KW - Metals -- metabolism KW - Hydroxylamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69649445?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Amyloid+beta+peptides+do+not+form+peptide-derived+free+radicals+spontaneously%2C+but+can+enhance+metal-catalyzed+oxidation+of+hydroxylamines+to+nitroxides.&rft.au=Dikalov%2C+S+I%3BVitek%2C+M+P%3BMaples%2C+K+R%3BMason%2C+R+P&rft.aulast=Dikalov&rft.aufirst=S&rft.date=1999-04-02&rft.volume=274&rft.issue=14&rft.spage=9392&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-27 N1 - Date created - 1999-04-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Transformation of MutL by ATP Binding and Hydrolysis: A Switch in DNA Mismatch Repair AN - 17282391; 4510784 AB - The MutL DNA mismatch repair protein has recently been shown to be an ATPase and to belong to an emerging ATPase superfamily that includes DNA topoisomerase II and Hsp90. We report here the crystal structures of a 40 kDa ATPase fragment of E. coli MutL (LN40) complexed with a substrate analog, ADPnP, and with product ADP. More than 60 residues that are disordered in the apoprotein structure become ordered and contribute to both ADPnP binding and dimerization of LN40. Hydrolysis of ATP, signified by subsequent release of the gamma -phosphate, releases two key loops and leads to dissociation of the LN40 dimer. Dimerization of the LN40 region is required for and is the rate-limiting step in ATP hydrolysis by MutL. The ATPase activity of MutL is stimulated by DNA and likely acts as a switch to coordinate DNA mismatch repair. JF - Cell AU - Ban, C AU - Junop, M AU - Yang, Wei AD - Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA, wei.yang@nih.gov Y1 - 1999/04/02/ PY - 1999 DA - 1999 Apr 02 SP - 85 EP - 97 VL - 97 IS - 1 SN - 0092-8674, 0092-8674 KW - MutL protein KW - mismatch repair KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - Transformation KW - DNA repair KW - Crystal structure KW - Escherichia coli KW - J 02725:DNA KW - J 02727:Amino acids, peptides and proteins KW - N 14940:Nucleic acid-binding proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282391?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell&rft.atitle=Transformation+of+MutL+by+ATP+Binding+and+Hydrolysis%3A+A+Switch+in+DNA+Mismatch+Repair&rft.au=Ban%2C+C%3BJunop%2C+M%3BYang%2C+Wei&rft.aulast=Ban&rft.aufirst=C&rft.date=1999-04-02&rft.volume=97&rft.issue=1&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Cell&rft.issn=00928674&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA repair; Transformation; Crystal structure ER - TY - JOUR T1 - Swainsonine protects both murine and human haematopoietic systems from chemotherapeutic toxicity. AN - 69858342; 10389983 AB - The haematopoietic system is sensitive to cytotoxic damage and is often the site of dose-limiting toxicity. We previously reported that swainsonine, an inhibitor of protein glycosylation, reduced the bone marrow toxicity resulting from a single dose of anticancer drugs in otherwise healthy mice. However, more important questions are (1) can swainsonine protect tumour-bearing mice without interfering with the anti-tumour effects of the drugs, and (2) can swainsonine stimulate haematopoietic activity of human, as well as murine, bone marrow. We demonstrate here that swainsonine protects C57BL/6 mice bearing melanoma-derived tumours from cyclophosphamide-induced toxicity without interfering with the drug's ability to inhibit tumour growth. Similar results were obtained in vivo with 3'-azido-3'-deoxythymidine (AZT), a myelosuppressive agent often used in therapy for acquired immune deficiency syndrome. Swainsonine increased both total bone marrow cellularity and the number of circulating white blood cells in mice treated with doses of AZT that typically lead to severe myelosuppression. Swainsonine also increased the number of erythroid and myeloid colony forming cells (CFCs) in short-term cultures of murine bone marrow, restoring the number of progenitor cells to the control level in the presence of AZT doses that reduced CFCs by 80%. With respect to the sensitivity of human haematopoietic cells to swainsonine, we show that swainsonine protected human myeloid progenitor cells from AZT toxicity in vitro. These results suggest that swainsonine may be useful as an adjuvant in several types of human chemotherapy. JF - British journal of cancer AU - Klein, J L AU - Roberts, J D AU - George, M D AU - Kurtzberg, J AU - Breton, P AU - Chermann, J C AU - Olden, K AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 87 EP - 95 VL - 80 IS - 1-2 SN - 0007-0920, 0007-0920 KW - Adjuvants, Immunologic KW - 0 KW - Antimetabolites KW - Antineoplastic Agents KW - Zidovudine KW - 4B9XT59T7S KW - Cyclophosphamide KW - 8N3DW7272P KW - Swainsonine KW - RSY4RK37KQ KW - Index Medicus KW - AIDS/HIV KW - Neoplasm Transplantation KW - Bone Marrow Cells -- drug effects KW - Animals KW - Drug Interactions KW - Tumor Cells, Cultured KW - Humans KW - Mice, Inbred C57BL KW - Mice KW - Female KW - Zidovudine -- adverse effects KW - Swainsonine -- pharmacology KW - Antimetabolites -- adverse effects KW - Melanoma -- drug therapy KW - Adjuvants, Immunologic -- pharmacology KW - Melanoma -- immunology KW - Hematopoietic Stem Cells -- drug effects KW - Cyclophosphamide -- adverse effects KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69858342?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Swainsonine+protects+both+murine+and+human+haematopoietic+systems+from+chemotherapeutic+toxicity.&rft.au=Klein%2C+J+L%3BRoberts%2C+J+D%3BGeorge%2C+M+D%3BKurtzberg%2C+J%3BBreton%2C+P%3BChermann%2C+J+C%3BOlden%2C+K&rft.aulast=Klein&rft.aufirst=J&rft.date=1999-04-01&rft.volume=80&rft.issue=1-2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-07 N1 - Date created - 1999-07-07 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1983 Jun 25;258(12):7578-85 [6408079] J Biol Chem. 1982 Jul 25;257(14):7936-9 [6806288] N Engl J Med. 1987 Jul 23;317(4):192-7 [3299090] Lancet. 1989 Jul 8;2(8654):91-2 [2567882] N Engl J Med. 1989 Sep 14;321(11):726-38 [2671731] N Engl J Med. 1990 May 24;322(21):1488-93 [2186273] Int J Cell Cloning. 1990 Sep;8(5):332-45 [2230284] J Infect Dis. 1991 Jul;164(1):43-52 [1676045] Lancet. 1991 Sep 7;338(8767):601-2 [1679155] J Natl Cancer Inst. 1991 Aug 21;83(16):1149-56 [1909378] Fundam Appl Toxicol. 1991 Jul;17(1):159-76 [1655546] Pharmacol Ther. 1991;50(3):285-90 [1754603] AIDS Res Hum Retroviruses. 1992 Jan;8(1):61-7 [1736941] Blood. 1992 May 15;79(10):2605-9 [1586712] Ann Intern Med. 1992 Sep 15;117(6):487-501 [1503352] AIDS Res Hum Retroviruses. 1992 Jun;8(6):1073-80 [1380256] Clin Oncol (R Coll Radiol). 1995;7(2):97-101 [7542473] Blood. 1995 Dec 15;86(12):4400-8 [8541527] Br J Haematol. 1996 Sep;94(3):443-8 [8790139] Br J Haematol. 1996 Sep;94(4):619-27 [8826883] Leuk Lymphoma. 1997 Apr;25(3-4):289-300 [9168439] Eur J Pediatr. 1997 Sep;156(9):693-700 [9296532] J Acquir Immune Defic Syndr. 1992;5(11):1148-57 [1383491] Exp Hematol. 1993 Feb;21(2):263-8 [7678812] Res Immunol. 1993 Jul-Sep;144(6-7):395-406 [8303059] Cancer Res. 1994 Mar 15;54(6):1450-7 [8137247] Genetica. 1995;95(1-3):91-101 [7744265] Proc Natl Acad Sci U S A. 1986 Mar;83(6):1752-6 [3081900] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis. AN - 69849846; 10381625 AB - Recent evidence suggests an intriguing link between p53 and the Fas pathway. To evaluate this association further, we utilized a recombinant adenoviral vector (AdWTp53) to overexpress wild-type p53 in lung cancer (A549, H23, EKVX and HOP92) and breast cancer (MDA-MB-231 and MCF-7) cell lines and observed an increase in the Fas/CD95/APO-1 protein levels. Furthermore, this increase correlated with the sensitivity of the cell lines to p53-mediated cytotoxicity. To examine the effects of Fas over-expression in cells resistant to p53 over-expression, we constructed AdFas, an adenoviral vector capable of transferring functional human Fas to cancer cells. Interestingly, infection of p53-resistant MCF-7 cells with AdFas sensitized them to p53-mediated apoptosis. These studies indicate that combined over-expression of Fas and wild-type p53 may be an effective cancer gene therapy approach, especially in cells relatively resistant to p53 over-expression. JF - Cell death and differentiation AU - Rakkar, A N AU - Katayose, Y AU - Kim, M AU - Craig, C AU - Ohri, E AU - Li, Z AU - Cowan, K H AU - Seth, P AD - Medical Breast Cancer Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institues of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 326 EP - 333 VL - 6 IS - 4 SN - 1350-9047, 1350-9047 KW - Antigens, CD95 KW - 0 KW - Cytotoxins KW - DNA Primers KW - DNA, Neoplasm KW - Tumor Suppressor Protein p53 KW - Index Medicus KW - Tumor Cells, Cultured -- cytology KW - Tumor Cells, Cultured -- chemistry KW - Lung Neoplasms KW - Humans KW - Adenoviridae Infections KW - Gene Expression KW - Genetic Therapy -- methods KW - Cytotoxins -- genetics KW - Breast Neoplasms KW - DNA, Neoplasm -- analysis KW - Female KW - Tumor Cells, Cultured -- virology KW - Adenoviridae KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis -- genetics KW - Antigens, CD95 -- genetics KW - Genetic Vectors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69849846?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+death+and+differentiation&rft.atitle=A+novel+adenoviral+vector+expressing+human+Fas%2FCD95%2FAPO-1+enhances+p53-mediated+apoptosis.&rft.au=Rakkar%2C+A+N%3BKatayose%2C+Y%3BKim%2C+M%3BCraig%2C+C%3BOhri%2C+E%3BLi%2C+Z%3BCowan%2C+K+H%3BSeth%2C+P&rft.aulast=Rakkar&rft.aufirst=A&rft.date=1999-04-01&rft.volume=6&rft.issue=4&rft.spage=326&rft.isbn=&rft.btitle=&rft.title=Cell+death+and+differentiation&rft.issn=13509047&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gamma radiation and MC540 photosensitization of melanoma in the hamster's eye. AN - 69839041; 10380933 AB - The purpose of this study was to evaluate the effects of cobalt-60 gamma-radiation and argon laser irradiation using injected merocyanine (MC540) as a photosensitizer on pigmented and non-pigmented Bomirski hamster melanomas growing in the eye. The animals were treated with one of four regimens, receiving gamma-irradiation only, photosensitization only, a combination of gamma-irradiation and photosensitization, or a combined time-fractionated treatment. Tumours were exposed to laser light 24 h after injection, when the photosensitizing dye concentration was highest. The degree of tissue damage was evaluated by observation of the area for necrosis, interruption of blood circulation, and the shape and dissemination of the tumour cells. Additionally, tumour growth was monitored through the measurement of tumour volume and also calculated from histological cross sections on the assumption that the tumour morphology is hemi-ellipsoidal. A single treatment of tumours by a combination of photodynamic therapy and ionizing radiation resulted in an additive effect, inhibiting tumour growth for 2-4 days. A time-fractionated treatment, given four times every 24 h, markedly delayed tumour growth for up to 6 weeks. The results indicate that MC540-mediated photodynamic treatment in combination with gamma-radiation exerts a significant therapeutic effect on a rapidly growing melanoma. JF - Melanoma research AU - Kukielczak, B AU - Romanowska, B AU - Bryk, J AD - Department of Radiospectroscopy and Radiobiology of Cancer, Institute of Molecular Biology, Jagiellonian University, Krakow, Poland. kukielcz@niehs.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 115 EP - 124 VL - 9 IS - 2 SN - 0960-8931, 0960-8931 KW - Index Medicus KW - Animals KW - Kinetics KW - Phototherapy -- adverse effects KW - Mesocricetus KW - Dose-Response Relationship, Radiation KW - Time Factors KW - Female KW - Cricetinae KW - Melanoma, Experimental -- radiotherapy KW - Gamma Rays -- adverse effects KW - Photosensitivity Disorders KW - Eye Neoplasms -- radiotherapy KW - Gamma Rays -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69839041?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Melanoma+research&rft.atitle=Gamma+radiation+and+MC540+photosensitization+of+melanoma+in+the+hamster%27s+eye.&rft.au=Kukielczak%2C+B%3BRomanowska%2C+B%3BBryk%2C+J&rft.aulast=Kukielczak&rft.aufirst=B&rft.date=1999-04-01&rft.volume=9&rft.issue=2&rft.spage=115&rft.isbn=&rft.btitle=&rft.title=Melanoma+research&rft.issn=09608931&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-01 N1 - Date created - 1999-09-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Neuroendocrine responses to intravenous infusion of physostigmine in patients with Alzheimer disease. AN - 69831701; 10372954 AB - We have reported that physostigmine, a reversible cholinesterase inhibitor, enhances verbal memory in patients with Alzheimer disease (AD). To elucidate the mechanism of cognition enhancement, plasma hormones were measured during high-dose acute and low-dose chronic steady-state intravenous infusions of physostigmine in nine subjects with AD. High-dose hormone responses were measured during and for 24 h after the infusion of physostigmine 1-1.5 mg over 45-60 min. Chronic responses were measured during continuous intravenous infusions of physostigmine at doses (0.5-25 mg/day) that escalated over 2 weeks, and then during 1 week infusion of the dose that optimized cognition (2-12 mg/day) or placebo administered in a randomized, double-blind, cross-over design. A replicable improvement in verbal memory was found in five subjects. High-dose physostigmine infusion that produced noxious side effects resulted in significant elevation above baseline in plasma levels of adrenocorticotrophic hormone (ACTH) (p = 0.0001), cortisol (p = 0.0001), and beta-endorphin (p = 0.0001). Chronic physostigmine administration, in the absence of adverse effects, produced no significant elevation in ACTH (p = 0.08), cortisol (p = 0.70), or beta-endorphin (p = 0.82). These results indicate that high-dose physostigmine activates the hypothalamic-pituitary-adrenal (HPA) axis, likely representing a "stress response." In contrast, cognition-enhancing doses do not produce a peripheral corticosteroid response. Thus, physostigmine-induced memory improvement is independent of the activation of the HPA axis. JF - Alzheimer disease and associated disorders AU - Asthana, S AU - Raffaele, K C AU - Greig, N H AU - Schapiro, M B AU - Blackman, M R AU - Soncrant, T T AD - Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA. PY - 1999 SP - 102 EP - 108 VL - 13 IS - 2 SN - 0893-0341, 0893-0341 KW - Cholinesterase Inhibitors KW - 0 KW - beta-Endorphin KW - 60617-12-1 KW - Adrenocorticotropic Hormone KW - 9002-60-2 KW - Physostigmine KW - 9U1VM840SP KW - Hydrocortisone KW - WI4X0X7BPJ KW - Index Medicus KW - Analysis of Variance KW - Drug Administration Schedule KW - Double-Blind Method KW - Memory -- drug effects KW - Dose-Response Relationship, Drug KW - Adrenocorticotropic Hormone -- drug effects KW - Humans KW - Linear Models KW - Aged KW - beta-Endorphin -- drug effects KW - beta-Endorphin -- blood KW - Hydrocortisone -- blood KW - Paired-Associate Learning -- drug effects KW - Cognition -- drug effects KW - Cross-Over Studies KW - Least-Squares Analysis KW - Adrenocorticotropic Hormone -- blood KW - Cholinesterase Inhibitors -- pharmacology KW - Alzheimer Disease -- blood KW - Hypothalamo-Hypophyseal System -- drug effects KW - Cholinesterase Inhibitors -- administration & dosage KW - Cholinesterase Inhibitors -- adverse effects KW - Physostigmine -- pharmacology KW - Physostigmine -- administration & dosage KW - Alzheimer Disease -- drug therapy KW - Pituitary-Adrenal System -- drug effects KW - Physostigmine -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69831701?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alzheimer+disease+and+associated+disorders&rft.atitle=Neuroendocrine+responses+to+intravenous+infusion+of+physostigmine+in+patients+with+Alzheimer+disease.&rft.au=Asthana%2C+S%3BRaffaele%2C+K+C%3BGreig%2C+N+H%3BSchapiro%2C+M+B%3BBlackman%2C+M+R%3BSoncrant%2C+T+T&rft.aulast=Asthana&rft.aufirst=S&rft.date=1999-04-01&rft.volume=13&rft.issue=2&rft.spage=102&rft.isbn=&rft.btitle=&rft.title=Alzheimer+disease+and+associated+disorders&rft.issn=08930341&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-20 N1 - Date created - 1999-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - An inhibitory monoclonal antibody to human cytochrome P450 2A6 defines its role in the metabolism of coumarin, 7-ethoxycoumarin and 4-nitroanisole in human liver. AN - 69829956; 10376770 AB - Cytochrome P450 (CYP) 2A6 is an important enzyme catalysing the metabolism of many drugs, procarcinogens and promutagens. Its role in human liver metabolism of coumarin, 4-nitroanisole, 4-nitrophenol and 7-ethoxycoumarin was analysed with an inhibitory monoclonal antibody (MAb) to CYP2A6. MAbs were derived from a panel of 16 hybridomas which yielded positive enzyme-linked immunosorbent assay (ELISA) results or immunoblots against CYP2A6. The hybridomas were selected from more than 500 clones generated by the fusion of myeloma cells with spleen cells of mice immunized with purified baculovirus-expressed human CYP2A6. The MAbs obtained from four of the 16 hybridomas exhibited strong inhibitory activity to CYP2A6-catalysed phenanthrene metabolism. MAb 151-45-4 was positive and highly specific to CYP2A6 as determined by ELISA and immunoblot, and showed no cross-reactivity with recombinant human CYP 1A1, 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5, as tested with ELISA and immunoblot analyses. MAb 151-45-4 specifically inhibited CYP2A6-catalysed metabolism of phenanthrene, 4-nitroanisole, 4-nitrophenol, coumarin and 7-ethoxycoumarin each by 94-99% and did not inhibit their metabolism catalysed by 10 other human CYPs. The potent inhibitory effect of MAb 151-45-4 was used to define the contribution of human CYP2A6 to the metabolism of coumarin, 4-nitroanisole and 7-ethoxycoumarin in seven human liver microsome samples. Coumarin metabolism in all of the seven samples was inhibited by greater than 94% by MAb 151-45-4 which indicates that essentially all microsome mediated coumarin metabolism in human liver is catalysed only by CYP2A6. Inhibition of 4-nitroanisole and 7-ethoxycoumarin metabolism by anti 2A6 MAb ranged from 22-65% and 8-24%, respectively. The degree of inhibition defines the contribution of CYP2A6 activity to the 4-nitroanisole and 7-ethoxycoumarin metabolism in human liver and the range reflects the variability among samples. The inhibitory antibody to CYP2E1 was used to determine its role in 4-nitroanisole and 7-ethoxycoumarin metabolism in seven human liver samples. The addition of both MAbs to CYP2A6 and 2E1 to the microsome samples defined combinatorially the relative role of CYP2A6 and 2E1 in the metabolism of 4-nitroanisole and 7-ethoxycoumarin. JF - Pharmacogenetics AU - Sai, Y AU - Yang, T J AU - Krausz, K W AU - Gonzalez, F J AU - Gelboin, H V AD - Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institute of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 229 EP - 237 VL - 9 IS - 2 SN - 0960-314X, 0960-314X KW - Anisoles KW - 0 KW - Antibodies, Monoclonal KW - Coumarins KW - 7-ethoxycoumarin KW - 31005-02-4 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - coumarin KW - A4VZ22K1WT KW - Mixed Function Oxygenases KW - EC 1.- KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP2A6 protein, human KW - Cytochrome P-450 CYP2A6 KW - 4-nitroanisole KW - G989Z7WOLH KW - Index Medicus KW - Animals KW - Hybridomas KW - Humans KW - Mice KW - Mice, Inbred BALB C KW - Female KW - Cross Reactions KW - Catalysis KW - Mixed Function Oxygenases -- immunology KW - Mixed Function Oxygenases -- metabolism KW - Microsomes, Liver -- metabolism KW - Coumarins -- metabolism KW - Microsomes, Liver -- enzymology KW - Cytochrome P-450 Enzyme System -- immunology KW - Cytochrome P-450 Enzyme System -- metabolism KW - Anisoles -- metabolism KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69829956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacogenetics&rft.atitle=An+inhibitory+monoclonal+antibody+to+human+cytochrome+P450+2A6+defines+its+role+in+the+metabolism+of+coumarin%2C+7-ethoxycoumarin+and+4-nitroanisole+in+human+liver.&rft.au=Sai%2C+Y%3BYang%2C+T+J%3BKrausz%2C+K+W%3BGonzalez%2C+F+J%3BGelboin%2C+H+V&rft.aulast=Sai&rft.aufirst=Y&rft.date=1999-04-01&rft.volume=9&rft.issue=2&rft.spage=229&rft.isbn=&rft.btitle=&rft.title=Pharmacogenetics&rft.issn=0960314X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-16 N1 - Date created - 1999-07-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - 3-Fluoro-3-deoxy-D-galactose: a new probe for studies on sugar cataract. AN - 69826337; 10372987 AB - Aldose reductase (AR) activity and flux through the polyol pathway can conveniently be monitored in dog lenses by measuring the metabolism of 3-fluoro-3-deoxy-D-glucose by 19F nuclear magnetic resonance (NMR) spectroscopy. Since AR has broad substrate specificity and preferentially utilizes galactose over glucose as substrate, the ability of AR to utilize 3-fluoro-3-deoxy-D-galactose (3-FDGal) as substrate as well as the metabolism of 3-FDGal in intact dog lens and cultured lens epithelial cells has been investigated. The suitableness of 3FDGal as a substrate was examined by incubating 3FDGal with purified dog lens aldose reductase in the presence of an NADPH generating system or with galactitol dehydrogenase in the presence of NAD+. Dog lenses and dog lens epithelial cells were cultured in 3-FDGal medium with and without the AR inhibitor AL 1576. Metabolism was studied using 19F NMR. AR activity with 3-FDGal as substrate is higher than that with D-galactose and its Km of 4.2 mM is ca 10-fold higher than that of D-galactose. Purified dog lens AR incubated with 3-FDGal resulted in the formation of 3-fluoro-3-deoxy-D-galactitol. Galactitol formation was prevented by the addition of AL 1576. Incubation of 3-FDGal with galactitol dehydrogenase resulted in the formation of 3-fluoro-3-deoxy-D-galactonic acid. Dog lenses cultured in 3-FDGal medium formed NMR peaks corresponding to 3-fluoro-3-deoxy-D-galactitol and 3-fluoro-3-deoxy-D-galactonic acid. The presence of AL 1576 inhibited the formation of galactitol but not galactonic acid. Lens epithelial cells cultured in 3-FDGal medium formed only 3-fluoro-3-deoxy-D-galactitol. These cells developed multiple cytoplasmic vacuoles which was prevented by the aldose reductase inhibitor AL 1576. The high affinity of this fluorinated sugar for aldose reductase makes this an excellent probe for investigating aldose reductase activity in dog lens tissues. JF - Current eye research AU - Secchi, E F AU - Lizak, M J AU - Sato, S AU - Kador, P F AD - Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1850, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 277 EP - 282 VL - 18 IS - 4 SN - 0271-3683, 0271-3683 KW - 3-fluoro-3-deoxygalactose KW - 0 KW - Fucose KW - 3713-31-3 KW - Sugar Alcohol Dehydrogenases KW - EC 1.1.- KW - galactitol 2-dehydrogenase KW - EC 1.1.1.16 KW - Aldehyde Reductase KW - EC 1.1.1.21 KW - Index Medicus KW - Fucose -- analogs & derivatives KW - Animals KW - Lens, Crystalline -- cytology KW - Cytoplasm -- ultrastructure KW - Sugar Alcohol Dehydrogenases -- metabolism KW - Aldehyde Reductase -- metabolism KW - Fucose -- metabolism KW - Epithelial Cells -- metabolism KW - Vacuoles -- ultrastructure KW - Epithelial Cells -- drug effects KW - Lens, Crystalline -- pathology KW - Lens, Crystalline -- metabolism KW - Cells, Cultured KW - Epithelial Cells -- pathology KW - Fucose -- pharmacology KW - Lens, Crystalline -- drug effects KW - In Vitro Techniques KW - Dogs KW - Cataract -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69826337?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+eye+research&rft.atitle=3-Fluoro-3-deoxy-D-galactose%3A+a+new+probe+for+studies+on+sugar+cataract.&rft.au=Secchi%2C+E+F%3BLizak%2C+M+J%3BSato%2C+S%3BKador%2C+P+F&rft.aulast=Secchi&rft.aufirst=E&rft.date=1999-04-01&rft.volume=18&rft.issue=4&rft.spage=277&rft.isbn=&rft.btitle=&rft.title=Current+eye+research&rft.issn=02713683&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-29 N1 - Date created - 1999-07-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - [The concept of "gateway drug"]. AN - 69803540; 10355245 AB - To develop drug abuse prevention for adolescents in Japan, the author reviewed concepts of "gateway drug" and "stepping-stone hypothesis". Firstly, results obtained from high school students in New York State (Kandel, D., 1975) were introduced as a standard model of "stepping-stone hypothesis". Secondly, results obtained from serious drug abusers in New York City (Golub, A. et al., 1994) were introduced as an example that shows the importance of defining clearly which cohort a study refers to when we use "gateway drug". Thirdly, results of a junior high school students survey in Japan were introduced and discussed to consider whether alcohol and cigarette for junior high school students in Japan are "gateway drugs" to solvent. The author concluded: 1) that cigarette smoking in junior high school students in Japan has a strong relationship with solvent inhalation, and 2) that drinking alcohol, however, depends on the presence of adults. Lastly, the author emphasized the need for doing more research on drug abuse in Japan. JF - Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence AU - Wada, K AD - Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, National Center of Neurology and Psychiatry, Chiba-ken, Japan. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 95 EP - 106 VL - 34 IS - 2 SN - 1341-8963, 1341-8963 KW - Solvents KW - 0 KW - Index Medicus KW - Smoking KW - Humans KW - Adult KW - Alcohol Drinking KW - Substance-Related Disorders UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69803540?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.atitle=%5BThe+concept+of+%22gateway+drug%22%5D.&rft.au=Wada%2C+K&rft.aulast=Wada&rft.aufirst=K&rft.date=1999-04-01&rft.volume=34&rft.issue=2&rft.spage=95&rft.isbn=&rft.btitle=&rft.title=Nihon+Arukoru+Yakubutsu+Igakkai+zasshi+%3D+Japanese+journal+of+alcohol+studies+%26+drug+dependence&rft.issn=13418963&rft_id=info:doi/ LA - Japanese DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Rhinal cortex lesions produce mild deficits in visual discrimination learning for an auditory secondary reinforcer in rhesus monkeys. AN - 69800086; 10357449 AB - Aspiration, but not neurotoxic, lesions of the amygdala impair performance on a visual discrimination learning task in which an auditory secondary reinforcer signals which of 2 stimuli will be reinforced with food. Because aspiration lesions of the amygdala interrupt projections of the rhinal cortex traveling close to the amygdala, it was hypothesized that damage to the rhinal cortex would severely impair learning in this task. Rhesus monkeys (Macaca mulatta) were trained to solve visual discrimination problems based on an auditory secondary reinforcer, were given lesions of the rhinal cortex or the perirhinal cortex alone, and were then retested. The monkeys displayed a reliable, albeit mild, deficit in postoperative performance. It is concluded that the aspiration lesions of the amygdala that produced a severe impairment did so because they interrupted connections of temporal cortical fields beyond the rhinal cortex that are also involved in learning in this task. JF - Behavioral neuroscience AU - Baxter, M G AU - Hadfield, W S AU - Murray, E A AD - Laboratory of Neuropsychology, National Institute of Mental Health, USA. mbaxter@wjh.harvard.edu Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 243 EP - 252 VL - 113 IS - 2 SN - 0735-7044, 0735-7044 KW - Index Medicus KW - Animals KW - Analysis of Variance KW - Reinforcement (Psychology) KW - Macaca mulatta KW - Acoustic Stimulation KW - Visual Perception KW - Male KW - Female KW - Entorhinal Cortex -- pathology KW - Discrimination Learning -- physiology KW - Entorhinal Cortex -- surgery KW - Entorhinal Cortex -- physiopathology KW - Psychomotor Performance -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69800086?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioral+neuroscience&rft.atitle=Rhinal+cortex+lesions+produce+mild+deficits+in+visual+discrimination+learning+for+an+auditory+secondary+reinforcer+in+rhesus+monkeys.&rft.au=Baxter%2C+M+G%3BHadfield%2C+W+S%3BMurray%2C+E+A&rft.aulast=Baxter&rft.aufirst=M&rft.date=1999-04-01&rft.volume=113&rft.issue=2&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Behavioral+neuroscience&rft.issn=07357044&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-15 N1 - Date created - 1999-07-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Discussion: severe mental retardation and cancer among atomic bomb survivors exposed in utero. AN - 69768651; 10331525 AB - When I was in medical school, Douglas Power Murphy, Professor of Obstetrics and Gynecology, told us of his inexpensive, simple study of "microcephaly" and mental retardation in newborn infants whose mothers had received therapeutic radiation early in pregnancy. His review of the literature and mail inquiry of other obstetrics centers in the United States revealed 14 published cases (Murphy, '28) and 16 unpublished (Goldstein and Murphy, '29). Here am I, 52 years later, still updating his findings. JF - Teratology AU - Miller, R W AD - National Cancer Institute, Bethesda, Maryland 20892-7236, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 234 EP - 235 VL - 59 IS - 4 SN - 0040-3709, 0040-3709 KW - Index Medicus KW - Humans KW - Adult KW - Middle Aged KW - Female KW - Pregnancy KW - Intellectual Disability -- etiology KW - Neoplasms, Radiation-Induced -- etiology KW - Nuclear Warfare KW - Neoplasms, Radiation-Induced -- epidemiology KW - Intellectual Disability -- epidemiology KW - Neoplasms, Radiation-Induced -- mortality KW - Survivors KW - Prenatal Exposure Delayed Effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69768651?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Teratology&rft.atitle=Discussion%3A+severe+mental+retardation+and+cancer+among+atomic+bomb+survivors+exposed+in+utero.&rft.au=Miller%2C+R+W&rft.aulast=Miller&rft.aufirst=R&rft.date=1999-04-01&rft.volume=59&rft.issue=4&rft.spage=234&rft.isbn=&rft.btitle=&rft.title=Teratology&rft.issn=00403709&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-09-08 N1 - Date created - 1999-09-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Truncation of the TGF-beta type II receptor gene results in insensitivity to TGF-beta in human gastric cancer cells. AN - 69751995; 10327067 AB - The transforming growth factor-beta (TGF-beta receptor system has been implicated in the development of resistance to the growth-inhibitory effects of TGF-beta. It has been reported that resistance to TGF-beta correlates with inactivation of the TGF-beta type II receptor (RII). In the present report, we examine the genetic changes in the TGF-beta RII gene of human gastric cancer cell lines, SNU-5 and SNU-668, which we had previously reported to express truncated TGF-beta RII transcripts. By independent PCR and Southern hybridization analysis of genomic DNA, we found that the genomic sequence of TGF-beta RII is truncated after exon 2 in SNU-5 and after exon 3 in SNU-668. This was confirmed by sequencing the TGF-beta RII cDNA cloned from a SNU-5 cDNA library. Predicted TGF-beta RII protein of SNU-5 cells based on sequencing data contains only a part of extracellular domain of TGF-beta RII. We demonstrate that cotransfection of 3TP-Lux and wild type TGF-beta RII restores the TGF-beta responsiveness in SNU-5 cells, suggesting that genetic changes in the TGF-beta RII gene of SNU-5 cells are responsible for the loss of sensitivity to TGF-beta. This is the first report demonstrating that truncation of the TGF-beta RII gene is an alternative mechanism to inactivate the TGF-beta signal transduction pathways. JF - Oncogene AU - Yang, H K AU - Kang, S H AU - Kim, Y S AU - Won, K AU - Bang, Y J AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/04/01/ PY - 1999 DA - 1999 Apr 01 SP - 2213 EP - 2219 VL - 18 IS - 13 SN - 0950-9232, 0950-9232 KW - DNA, Neoplasm KW - 0 KW - Neoplasm Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Receptors, Transforming Growth Factor beta KW - Transforming Growth Factor beta KW - Protein-Serine-Threonine Kinases KW - EC 2.7.11.1 KW - transforming growth factor-beta type II receptor KW - EC 2.7.11.30 KW - Index Medicus KW - Polymerase Chain Reaction KW - Base Sequence KW - Tumor Cells, Cultured KW - Blotting, Southern KW - Humans KW - Signal Transduction -- genetics KW - Molecular Sequence Data KW - DNA, Neoplasm -- genetics KW - Amino Acid Sequence KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - Transforming Growth Factor beta -- pharmacology KW - Stomach Neoplasms -- pathology KW - Receptors, Transforming Growth Factor beta -- genetics KW - Stomach Neoplasms -- metabolism KW - Neoplasm Proteins -- physiology KW - Carcinoma -- pathology KW - Stomach Neoplasms -- genetics KW - Receptors, Transforming Growth Factor beta -- physiology KW - Neoplasm Proteins -- genetics KW - Carcinoma -- metabolism KW - Sequence Deletion KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69751995?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Truncation+of+the+TGF-beta+type+II+receptor+gene+results+in+insensitivity+to+TGF-beta+in+human+gastric+cancer+cells.&rft.au=Yang%2C+H+K%3BKang%2C+S+H%3BKim%2C+Y+S%3BWon%2C+K%3BBang%2C+Y+J%3BKim%2C+S+J&rft.aulast=Yang&rft.aufirst=H&rft.date=1999-04-01&rft.volume=18&rft.issue=13&rft.spage=2213&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-26 N1 - Date created - 1999-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The oncostatic action of melatonin in an ovarian carcinoma cell line. AN - 69743235; 10231725 AB - Melatonin is reported to reduce proliferation in many cell types, but the effect is small and the results are inconsistent. Information on the mechanism by which melatonin exerts its antiproliferative effects might provide insight into the variability of the response. In an ovarian adenocarcinoma cell line (BG-1), we find that melatonin at concentrations of 10(-9)-10(-7) M caused a 20-25% reduction in cell number. Melatonin also resulted in a similar reduction in [3H]-thymidine incorporation with no significant increase in cell death as measured by trypan blue incorporation. The Kd for melatonin reduction in cell number was approximately 5 x 10(-10) M. Melatonin ML2 receptors have a Kd for melatonin binding in the low nM range and are linked to the production of the calcium mobilizing agent inositol-1,4,5-trisphosphate (IP3). To investigate whether melatonin signaling involves an increase in cytosolic-free calcium. BG-1 cells were loaded with the calcium sensitive indicator, fura-2. Acute addition of melatonin (10(-5)-10(-9) M) did not alter cytosolic calcium. Addition of the putative nuclear receptor agonist CGP52608 caused a dose-dependent inhibition of cell number with a Kd of approximately 2 x 10(-9) M. Addition of CGP52608 caused a similar reduction in [3H]-thymidine incorporation. Neither melatonin (10(-8) M-10(-5) M) nor CGP52608 at concentrations below 10(-7) M induced cell death associated with the inhibition of cell proliferation; however, addition of CGP52608 at a high dose (10(-7) M) caused an increase in cell death, consistent with apoptosis. Growth inhibition by melatonin or CGP52608 did not alter the percentage of cells in G1 versus S/G2/M. JF - Journal of pineal research AU - Petranka, J AU - Baldwin, W AU - Biermann, J AU - Jayadev, S AU - Barrett, J C AU - Murphy, E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 129 EP - 136 VL - 26 IS - 3 SN - 0742-3098, 0742-3098 KW - Antineoplastic Agents KW - 0 KW - Thiazoles KW - Thiosemicarbazones KW - CGP 52608 KW - 87958-67-6 KW - DNA KW - 9007-49-2 KW - Trypan Blue KW - I2ZWO3LS3M KW - Melatonin KW - JL5DK93RCL KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Cell Division -- drug effects KW - DNA -- biosynthesis KW - Thiazoles -- pharmacology KW - Calcium -- metabolism KW - Tumor Cells, Cultured KW - Cell Count -- drug effects KW - Apoptosis -- drug effects KW - Signal Transduction -- drug effects KW - Flow Cytometry KW - Thiosemicarbazones -- pharmacology KW - Antineoplastic Agents -- pharmacology KW - Cell Cycle -- drug effects KW - Female KW - Melatonin -- agonists KW - Ovarian Neoplasms -- metabolism KW - Melatonin -- pharmacology KW - Adenocarcinoma -- metabolism KW - Ovarian Neoplasms -- pathology KW - Adenocarcinoma -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69743235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+pineal+research&rft.atitle=The+oncostatic+action+of+melatonin+in+an+ovarian+carcinoma+cell+line.&rft.au=Petranka%2C+J%3BBaldwin%2C+W%3BBiermann%2C+J%3BJayadev%2C+S%3BBarrett%2C+J+C%3BMurphy%2C+E&rft.aulast=Petranka&rft.aufirst=J&rft.date=1999-04-01&rft.volume=26&rft.issue=3&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Journal+of+pineal+research&rft.issn=07423098&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-14 N1 - Date created - 1999-06-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Microdissection-based analysis of mature ovarian teratoma. AN - 69742646; 10233836 AB - The genotypic features of mature ovarian teratomas (MOTs) are controversial. Early studies detected a homozygous genotype in MOTs suggesting that these tumors are composed of germ cells that have undergone meiosis I. Other studies, however, revealed a heterozygous genotype in a substantial proportion of MOTs suggesting an origin either from premeiotic germ cells or from a somatic cell line. In view of the complex morphology of MOTs and to increase the sensitivity of teratoma genotyping, we applied tissue microdissection before genetic analysis of teratomatous tissue. This approach allowed selective analysis of different heterotopic tissue elements as well as the lymphoid tissues within MOTs the origin of which is unknown. After DNA extraction, the tissue samples were polymerase chain reaction amplified using a random panel of highly informative genetic markers for different chromosomes to evaluate heterozygosity versus homozygosity. In all seven cases that were analyzed, heterotopic tissues consistently revealed a homozygous genotype with several markers; in two cases, heterozygosity was detected with a single marker, indicating a meiotic recombination event. Lymphoid aggregates within MOTs were heterozygous and derived from host tissue rather than from teratomatous growth. However, well differentiated thymic tissue was consistently homozygous, suggesting lymphoid differentiation capability of MOTs. We conclude that potential pitfalls in genotyping of teratomas including meiotic recombination and host cell participation can be avoided by a microdissection-based approach in combination with a panel of genetic markers. JF - The American journal of pathology AU - Vortmeyer, A O AU - Devouassoux-Shisheboran, M AU - Li, G AU - Mohr, V AU - Tavassoli, F AU - Zhuang, Z AD - Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 987 EP - 991 VL - 154 IS - 4 SN - 0002-9440, 0002-9440 KW - Genetic Markers KW - 0 KW - DNA KW - 9007-49-2 KW - Abridged Index Medicus KW - Index Medicus KW - Lymphoid Tissue -- pathology KW - Homozygote KW - Humans KW - Child KW - Genotype KW - Polymerase Chain Reaction KW - Alleles KW - Heterozygote KW - Adult KW - DNA -- genetics KW - Adolescent KW - Dissection KW - Female KW - Teratoma -- genetics KW - Teratoma -- pathology KW - Ovarian Neoplasms -- genetics KW - Ovarian Neoplasms -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69742646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Microdissection-based+analysis+of+mature+ovarian+teratoma.&rft.au=Vortmeyer%2C+A+O%3BDevouassoux-Shisheboran%2C+M%3BLi%2C+G%3BMohr%2C+V%3BTavassoli%2C+F%3BZhuang%2C+Z&rft.aulast=Vortmeyer&rft.aufirst=A&rft.date=1999-04-01&rft.volume=154&rft.issue=4&rft.spage=987&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-10 N1 - Date created - 1999-06-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1969 Jul;63(3):699-704 [5259759] Cell Vis. 1998 Jan-Feb;5(1):43-8 [9660725] Nature. 1975 Apr 17;254(5501):597-8 [1128655] Cytogenet Cell Genet. 1976;16(1-5):391-5 [975915] Nature. 1977 Oct 6;269(5628):517-8 [909601] Birth Defects Orig Artic Ser. 1978;14(6B):297-301 [728570] Proc Natl Acad Sci U S A. 1982 Dec;79(23):7400-4 [6961419] J Med Genet. 1984 Feb;21(1):4-12 [6363699] Cancer Genet Cytogenet. 1990 May;46(1):115-23 [1970513] Am J Hum Genet. 1990 Oct;47(4):635-43 [2220805] Am J Hum Genet. 1990 Oct;47(4):644-55 [1977308] Am J Pathol. 1995 Mar;146(3):620-5 [7887444] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8167-74 [8710842] Adv Genet. 1997;35:253-84 [9348650] Ann Hum Genet. 1970 Jul;34(1):21-30 [5476662] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Nonrandom cytogenetic alterations in hepatocellular carcinoma from transgenic mice overexpressing c-Myc and transforming growth factor-alpha in the liver. AN - 69741145; 10233843 AB - Identification of specific and primary chromosomal alterations during the course of neoplastic development is an essential part of defining the genetic basis of cancer. We have developed a transgenic mouse model for liver neoplasia in which chromosomal lesions associated with both the initial stages of the neoplastic process and the acquisition of malignancy can be analyzed. Here we analyze chromosomal alterations in 11 hepatocellular carcinomas from the c-myc/TGF-alpha double-transgenic mice by fluorescent in situ hybridization with whole chromosome probes, single-copy genes, and 4'-6-diamidino-2-phenylindole (DAPI-) and G-banded chromosomes and report nonrandom cytogenetic alterations associated with the tumor development. All tumors were aneuploid and exhibited nonrandom structural and numerical alterations. A balanced translocation t(5:6)(G1;F2) was identified by two-color fluorescent in situ hybridization in all tumors, and, using a genomic probe, the c-myc transgene was localized near the breakpoint on derivative chromosome der 6. Partial or complete loss of chromosome 4 was observed in all tumors with nonrandom breakage in band C2. Deletions of chromosome 1 were observed in 80% of the tumors, with the most frequent deletion at the border of bands C4 and C5. An entire copy of chromosome 7 was lost in 80% of the tumors cells. Eighty-five percent of the tumor cells had lost one copy of chromosome 12, and the most common breakpoint on chromosome 12 occurred at band D3 (28%). A copy of chromosome 14 was lost in 72%, and band 14E1 was deleted in 32% of the tumor cells. The X chromosome was lost in the majority of the tumor cells. The most frequent deletion on the X chromosome involved band F1. We have previously shown that breakages of chromosomes 1, 6, 7, and 12 were observed before the appearance of morphologically distinct neoplastic liver lesions in this transgenic mouse model. Thus breakpoints on chromosome 4, 9, 14, and X appear to be later events in this model of liver neoplasia. This is the first study to demonstrate that specific sites of chromosomal breakage observed during a period of chromosomal instability in early stages of carcinogenesis are later involved in stable rearrangements in solid tumors. The identification of the 5;6 translocation in all of the tumors has a special significance, being the first balanced translocation reported in human and mouse hepatocellular carcinoma and having the breakpoint near a tumor susceptibility gene and myc transgene site of integration. Moreover, its early occurrence indicates that this is a primary and relevant alteration to the initiation of the neoplastic process. In addition, the concordance between the breakpoints observed during the early dysplastic stage of hepatocarcinogenesis and the stable deletions of chromosomes 1, 4, 6, 7, 9, and 12 in the tumors provides evidence for preferential site of genetic changes in hepatocarcinogenesis. JF - The American journal of pathology AU - Sargent, L M AU - Zhou, X AU - Keck, C L AU - Sanderson, N D AU - Zimonjic, D B AU - Popescu, N C AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1047 EP - 1055 VL - 154 IS - 4 SN - 0002-9440, 0002-9440 KW - Transforming Growth Factor alpha KW - 0 KW - Abridged Index Medicus KW - Index Medicus KW - Karyotyping KW - Translocation, Genetic -- genetics KW - Animals KW - Chromosome Deletion KW - Age Factors KW - In Situ Hybridization, Fluorescence KW - Mice KW - Mice, Transgenic KW - Chromosome Mapping KW - Chromosome Breakage -- genetics KW - Liver Neoplasms -- pathology KW - Transforming Growth Factor alpha -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Genes, myc -- genetics KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69741145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+pathology&rft.atitle=Nonrandom+cytogenetic+alterations+in+hepatocellular+carcinoma+from+transgenic+mice+overexpressing+c-Myc+and+transforming+growth+factor-alpha+in+the+liver.&rft.au=Sargent%2C+L+M%3BZhou%2C+X%3BKeck%2C+C+L%3BSanderson%2C+N+D%3BZimonjic%2C+D+B%3BPopescu%2C+N+C%3BThorgeirsson%2C+S+S&rft.aulast=Sargent&rft.aufirst=L&rft.date=1999-04-01&rft.volume=154&rft.issue=4&rft.spage=1047&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+pathology&rft.issn=00029440&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-10 N1 - Date created - 1999-06-10 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Surgery. 1995 Jun;117(6):601-8 [7778023] Ann Surg. 1995 Aug;222(2):171-8 [7639583] Br J Cancer. 1995 Aug;72(2):383-5 [7640222] Oncogene. 1995 Aug 17;11(4):711-21 [7651735] Cancer Genet Cytogenet. 1995 Sep;83(2):172-3 [7553591] Oncogene. 1995 Dec 7;11(11):2281-7 [8570178] Mutat Res. 1995 Dec;333(1-2):181-8 [8538626] Cell. 1996 Feb 23;84(4):587-97 [8598045] Cancer Res. 1996 May 1;56(9):2137-42 [8616862] J Exp Med. 1996 Mar 1;183(3):1141-50 [8642256] Genes Chromosomes Cancer. 1997 Aug;19(4):286-90 [9258665] Cancer Res. 1997 Aug 15;57(16):3451-6 [9270012] Cancer Res. 1997 Oct 1;57(19):4164-6 [9331067] Cancer Res. 1998 Jan 1;58(1):123-34 [9426068] Mol Carcinog. 1996 Jun;16(2):83-90 [8645430] Cancer Genet Cytogenet. 1996 Jun;88(2):170-4 [8640730] Genomics. 1996 Apr 15;33(2):328-9 [8660988] Gastroenterology. 1996 Aug;111(2):455-61 [8690212] Am J Pathol. 1996 Aug;149(2):407-28 [8701981] Biol Pharm Bull. 1996 May;19(5):683-91 [8741575] Cancer Lett. 1996 Aug 23;106(1):43-9 [8827045] Cancer Res. 1996 Oct 15;56(20):4575-7 [8840963] J Hepatol. 1996 Nov;25(5):655-62 [8938542] Nat Genet. 1996 Dec;14(4):468-70 [8944029] Int J Cancer. 1997 Feb 20;74(1):45-9 [9036868] Anticancer Res. 1996 Nov-Dec;16(6A):3271-82 [9042300] Carcinogenesis. 1997 Jan;18(1):115-20 [9054597] Mol Carcinog. 1997 May;19(1):17-24 [9180924] Proc Natl Acad Sci U S A. 1989 Nov;86(22):8852-6 [2573067] Jpn J Cancer Res. 1990 Feb;81(2):108-11 [1970554] Cell. 1990 May 4;61(3):407-17 [2185890] Cell. 1990 Jun 15;61(6):1137-46 [2350785] J Cell Sci. 1977 Apr;24:217-54 [893544] Chromosoma. 1984;89(4):294-320 [6745006] Science. 1987 Apr 10;236(4798):175-80 [3031816] Science. 1987 Sep 11;237(4820):1309-16 [3629242] Somat Cell Mol Genet. 1987 Sep;13(5):581-6 [2821634] Genomics. 1987 Sep;1(1):3-18 [3311967] Carcinogenesis. 1988 Jun;9(6):939-45 [3370757] Cytogenet Cell Genet. 1988;48(2):72-8 [2904349] Carcinogenesis. 1989 Feb;10(2):387-91 [2563236] Annu Rev Genet. 1988;22:479-519 [3071256] Oncogene. 1989 Jun;4(6):715-24 [2543942] Genomics. 1989 Feb;4(2):221-3 [2567701] Am J Hum Genet. 1989 Jul;45(1):73-82 [2545098] Carcinogenesis. 1990 Jul;11(7):1145-8 [2164892] Proc Natl Acad Sci U S A. 1990 Sep;87(17):6791-4 [2168560] Cancer Res. 1990 Nov 15;50(22):7184-9 [1977515] Cancer Res. 1991 Jan 1;51(1):89-93 [1670995] Oncogene. 1991 May;6(5):765-70 [1646986] Cancer Res. 1991 Aug 15;51(16):4367-70 [1678314] Science. 1991 Nov 22;254(5035):1161-7 [1957168] Mamm Genome. 1992;3(1):48-51 [1581633] Cancer Res. 1992 Oct 1;52(19):5368-72 [1356616] Genomics. 1992 Nov;14(3):611-7 [1358808] Mol Cell Biol. 1993 Jan;13(1):320-30 [8417334] Cancer Res. 1993 Jan 15;53(2):209-11 [8417808] Cancer Res. 1993 Apr 15;53(8):1719-23 [8467484] Hum Genet. 1993 Apr;91(3):275-7 [8386696] Cancer Res. 1993 May 1;53(9):1990-4 [8097672] Oncogene. 1993 Aug;8(8):2253-8 [8101648] Science. 1993 Oct 1;262(5130):57-66 [8211130] Cytogenet Cell Genet. 1994;65(3):184-5 [8222757] Cell. 1993 Nov 19;75(4):631-9 [8242739] Cancer Res. 1994 Jan 1;54(1):281-5 [7903205] Cancer Res. 1994 Feb 15;54(4):969-75 [8313388] Br J Cancer. 1994 Jun;69(6):1166-70 [8198986] Genomics. 1994 Mar 1;20(1):114-5 [8020936] Cancer Res. 1994 Aug 1;54(15):4177-82 [8033150] Cancer Res. 1994 Aug 1;54(15):4188-92 [7913413] Carcinogenesis. 1994 Aug;15(8):1637-45 [8055644] Drug Metab Rev. 1994;26(1-2):201-8 [8082565] Cancer Res. 1994 Oct 1;54(19):5041-4 [7923113] Cancer Res. 1994 Dec 1;54(23):6257-64 [7954475] Nature. 1994 Nov 10;372(6502):143-9 [7969446] Cancer Res. 1994 Dec 15;54(24):6489-95 [7987847] Clin Chim Acta. 1994 Aug;228(2):91-9 [7988039] Genomics. 1994 Oct;23(3):691-3 [7851898] Genetics. 1995 Jan;139(1):387-95 [7705639] Cancer Genet Cytogenet. 1995 Apr;80(2):100-2 [7736422] Mol Carcinog. 1995 May;13(1):37-43 [7766309] Comment In: Am J Pathol. 1999 Apr;154(4):975-7 [10233833] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of alcohol use and gender on the dynamics of EKG time-series data. AN - 69740390; 10235312 AB - Hurst analysis of EKG data obtained from a population of alcoholic (n = 13) and nonalcoholic (n = 48) subjects was undertaken. Potential subjects (n = 120) were screened using the Schedule for Affective Disorders and Schizophrenia and Structured Clinical Interview for DSM-III instruments. Data from subjects with a diagnosis of current alcohol dependence were analyzed. Subjects with diagnoses such as major depression, bipolar disorder or schizophrenia (Axis I diagnoses), or personality disorders (Axis II diagnoses) were excluded from analysis. Subjects undergoing testing were free of alcohol and illicit drugs. Alcoholic subjects had no clinical evidence of alcohol withdrawal symptoms at the time of testing. EKG data were obtained with eyes open or with eyes closed. Approximately 3.5 min of data were obtained for each condition. Alcoholic subjects had less complex heart rate dynamics as evidenced by higher values of H = 0.18 +/- 0.05 (mean +/- SEM), compared with healthy comparison subjects with H = 0.09 +/- 0.02, p < 0.014 for the eyes closed condition, and H = 0.17 +/- 0.05 (mean +/- SEM) compared with healthy comparison subjects with H = 0.07 +/- 0.02,p < 0.011 for the eyes open condition. A gender effect was seen, with female subjects showing evidence of more complex heart rate dynamics than male subjects. JF - Alcoholism, clinical and experimental research AU - DePetrillo, P B AU - White, K V AU - Liu, M AU - Hommer, D AU - Goldman, D AD - Laboratory of Clinical Studies, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1256, USA. pbdp@helix.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 745 EP - 750 VL - 23 IS - 4 SN - 0145-6008, 0145-6008 KW - Ethanol KW - 3K9958V90M KW - Index Medicus KW - Fractals KW - Sex Factors KW - Humans KW - Nonlinear Dynamics KW - Alcohol Drinking -- physiopathology KW - Temperance KW - Male KW - Female KW - Electrocardiography -- statistics & numerical data KW - Heart Rate -- drug effects KW - Ethanol -- pharmacology KW - Heart Rate -- physiology KW - Alcoholism -- physiopathology KW - Electrocardiography -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69740390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Effects+of+alcohol+use+and+gender+on+the+dynamics+of+EKG+time-series+data.&rft.au=DePetrillo%2C+P+B%3BWhite%2C+K+V%3BLiu%2C+M%3BHommer%2C+D%3BGoldman%2C+D&rft.aulast=DePetrillo&rft.aufirst=P&rft.date=1999-04-01&rft.volume=23&rft.issue=4&rft.spage=745&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-28 N1 - Date created - 1999-06-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alteration of proteolytic processing of c-Myb as a consequence of its truncation in murine myeloid leukemia. AN - 69734393; 10232384 JF - Leukemia AU - Bies, J AU - Nazarov, V AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, MD, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - S116 EP - S117 VL - 13 Suppl 1 SN - 0887-6924, 0887-6924 KW - Interleukin-6 KW - 0 KW - Neoplasm Proteins KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-myb KW - Trans-Activators KW - Endopeptidases KW - EC 3.4.- KW - Index Medicus KW - Animals KW - Cell Differentiation KW - Interleukin-6 -- pharmacology KW - Mice KW - Leucine Zippers KW - Neoplastic Stem Cells -- drug effects KW - Neoplastic Stem Cells -- metabolism KW - Exons -- genetics KW - Peptide Chain Termination, Translational KW - Phosphorylation KW - Cell Cycle KW - Mutagenesis, Insertional KW - Trans-Activators -- metabolism KW - Proto-Oncogene Proteins -- chemistry KW - Protein Processing, Post-Translational KW - Endopeptidases -- metabolism KW - Trans-Activators -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Leukemia, Myeloid -- metabolism KW - Leukemia, Myeloid -- genetics KW - Neoplasm Proteins -- chemistry KW - Neoplasm Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69734393?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Leukemia&rft.atitle=Alteration+of+proteolytic+processing+of+c-Myb+as+a+consequence+of+its+truncation+in+murine+myeloid+leukemia.&rft.au=Bies%2C+J%3BNazarov%2C+V%3BWolff%2C+L&rft.aulast=Bies&rft.aufirst=J&rft.date=1999-04-01&rft.volume=13+Suppl+1&rft.issue=&rft.spage=S116&rft.isbn=&rft.btitle=&rft.title=Leukemia&rft.issn=08876924&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-27 N1 - Date created - 1999-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - EPR characterization of free radical intermediates formed during ultrasound exposure of cell culture media. AN - 69733790; 10232837 AB - Free radicals and/or hydrogen peroxide produced by exposure of cells to ultrasound are potentially cytotoxic and mutagenic. The formation and type of free radical species can be substantially modulated by the chemical composition of the media in which the ultrasound exposures of cells are carried out. In the current study, we examined the free radical intermediates formed during ultrasound exposure of a typical cell culture medium (RPMI-1640); the dominant free radicals that were identified by spin trapping were derived from the hydrophobic amino acids Trp, Leu, and Phe, and were formed by hydrogen abstraction from these amino acids. Compared to exposures in phosphate-buffered saline, the yield of *OH radicals and H2O2 was significantly reduced in the cell culture medium, glucose (the main organic component in the medium), and the hydrophobic amino acids (Trp, Phe, Tyr, Leu, Val, Met) being chiefly responsible for this effect. In contrast, other nonhydrophobic amino acids did not contribute significantly to the *OH or H2O2 decrease. These findings are consistent with the accumulation of hydrophobic solutes at the liquid-gas interface of the collapsing cavitation bubbles resulting in increased efficiency of radical scavenging. JF - Free radical biology & medicine AU - Misík, V AU - Riesz, P AD - Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1002, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 936 EP - 943 VL - 26 IS - 7-8 SN - 0891-5849, 0891-5849 KW - Amino Acids KW - 0 KW - Benzenesulfonates KW - Culture Media KW - Cyclic N-Oxides KW - Formates KW - Free Radicals KW - Nitroso Compounds KW - Spin Labels KW - formic acid KW - 0YIW783RG1 KW - Hydroxyl Radical KW - 3352-57-6 KW - 5,5-dimethyl-1-pyrroline-1-oxide KW - 7170JZ1QF3 KW - 3,5-dibromo-4-nitrosobenzenesulfonate KW - 83016-63-1 KW - Index Medicus KW - Free Radicals -- analysis KW - Photolysis KW - Electron Spin Resonance Spectroscopy -- methods KW - Formates -- chemistry KW - Calorimetry KW - Models, Chemical KW - Culture Media -- radiation effects KW - Ultrasonics KW - Amino Acids -- chemistry KW - Hydroxyl Radical -- analysis KW - Culture Media -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69733790?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Free+radical+biology+%26+medicine&rft.atitle=EPR+characterization+of+free+radical+intermediates+formed+during+ultrasound+exposure+of+cell+culture+media.&rft.au=Mis%C3%ADk%2C+V%3BRiesz%2C+P&rft.aulast=Mis%C3%ADk&rft.aufirst=V&rft.date=1999-04-01&rft.volume=26&rft.issue=7-8&rft.spage=936&rft.isbn=&rft.btitle=&rft.title=Free+radical+biology+%26+medicine&rft.issn=08915849&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-23 N1 - Date created - 1999-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Advances in research on alcoholism and what they promise for future treatment and prevention. AN - 69732847; 10228334 JF - Medicine and health, Rhode Island AU - Gordis, E AD - National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 121 VL - 82 IS - 4 SN - 1086-5462, 1086-5462 KW - Index Medicus KW - United States KW - Research Design -- trends KW - Humans KW - Research Design -- standards KW - Forecasting KW - Alcoholism -- rehabilitation KW - Primary Prevention -- methods KW - Alcoholism -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69732847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Medicine+and+health%2C+Rhode+Island&rft.atitle=Advances+in+research+on+alcoholism+and+what+they+promise+for+future+treatment+and+prevention.&rft.au=Gordis%2C+E&rft.aulast=Gordis&rft.aufirst=E&rft.date=1999-04-01&rft.volume=82&rft.issue=4&rft.spage=121&rft.isbn=&rft.btitle=&rft.title=Medicine+and+health%2C+Rhode+Island&rft.issn=10865462&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-26 N1 - Date created - 1999-05-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - HGF-mediated apoptosis via p53/bax-independent pathway activating JNK1. AN - 69725526; 10223185 AB - Current studies have indicated both positive and negative roles for the hepatocyte growth factor (HGF)/c-met receptor signaling system in tumor development. Recently, we have shown that HGF has the capacity to induce both growth inhibition and programmed cell death in aflatoxin-transformed (AFLB8) rat liver epithelial cells. Using the same cell line, we have now investigated a potential mechanism for HGF-induced apoptosis. Immunoblot analysis of bcl-2 gene family member (bax, bcl-2, bclX-s/l) expression showed no correlation with HGF treatment, suggesting that HGF-mediated apoptosis is bax independent. Following HGF treatment retinoblastoma protein (pRB) was present in the hypophosphorylated state. HGF treatment increased cyclin A, cyclin G1 and nuclear transcriptional factor (NFkappaB) protein expression. However, electrophoretic mobility shift analysis showed that NFkappaB activity decreased with HGF treatment. Under these apoptotic conditions, c-Jun N-terminal kinase (JNK1) and extracellular signal-regulated kinase (ERK2) were activated with lower level activation of ERK2, while no involvement of phosphatidylinositol-3 kinase was observed. Epidermal growth factor (EGF) was not protective, and actually induced cells to undergo apoptosis to a level similar to that of HGF alone or EGF/HGF in combination. These results suggest the possibility of cross-talk between HGF/c-met and EGF/EGFR signaling pathways, and the involvement of JNK1 induction in HGF-mediated apoptotic cell death. JF - Carcinogenesis AU - Conner, E A AU - Teramoto, T AU - Wirth, P J AU - Kiss, A AU - Garfield, S AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 583 EP - 590 VL - 20 IS - 4 SN - 0143-3334, 0143-3334 KW - Aflatoxins KW - 0 KW - Bax protein, rat KW - Cyclins KW - NF-kappa B KW - Proto-Oncogene Proteins KW - Proto-Oncogene Proteins c-bcl-2 KW - Recombinant Proteins KW - Retinoblastoma Protein KW - Tumor Suppressor Protein p53 KW - bcl-2-Associated X Protein KW - Epidermal Growth Factor KW - 62229-50-9 KW - Hepatocyte Growth Factor KW - 67256-21-7 KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinase 1 KW - Mitogen-Activated Protein Kinases KW - Index Medicus KW - Protein Processing, Post-Translational -- drug effects KW - Animals KW - Cyclins -- biosynthesis KW - Recombinant Proteins -- pharmacology KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Receptor, Epidermal Growth Factor -- physiology KW - Epidermal Growth Factor -- pharmacology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - NF-kappa B -- genetics KW - Phosphorylation -- drug effects KW - Rats KW - Genes, bcl-2 KW - NF-kappa B -- biosynthesis KW - Cell Line, Transformed -- drug effects KW - Retinoblastoma Protein -- metabolism KW - Enzyme Activation -- drug effects KW - Aflatoxins -- toxicity KW - Cyclins -- genetics KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Tumor Suppressor Protein p53 -- physiology KW - Liver -- cytology KW - Liver -- drug effects KW - Hepatocyte Growth Factor -- pharmacology KW - Apoptosis -- physiology KW - Signal Transduction -- drug effects KW - Apoptosis -- drug effects KW - Calcium-Calmodulin-Dependent Protein Kinases -- physiology KW - Proto-Oncogene Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69725526?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=HGF-mediated+apoptosis+via+p53%2Fbax-independent+pathway+activating+JNK1.&rft.au=Conner%2C+E+A%3BTeramoto%2C+T%3BWirth%2C+P+J%3BKiss%2C+A%3BGarfield%2C+S%3BThorgeirsson%2C+S+S&rft.aulast=Conner&rft.aufirst=E&rft.date=1999-04-01&rft.volume=20&rft.issue=4&rft.spage=583&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene. AN - 69719954; 10223196 AB - Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras proto-oncogenes in chloroprene-induced lung and HG neoplasms. K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82). Both K- and H-ras codon 61 A-->T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A-->T transversion at K-ras codon 61. This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A-->T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A-->T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A-->T transversion at K-ras codon 61. This differed from 1,3-butadiene, where K-ras codon 13 G-->C transitions and H-ras codon 61 A-->G transitions were the predominant mutations. The major finding of K-ras A-->T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens. JF - Carcinogenesis AU - Sills, R C AU - Hong, H L AU - Melnick, R L AU - Boorman, G A AU - Devereux, T R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. sills@niehs.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 657 EP - 662 VL - 20 IS - 4 SN - 0143-3334, 0143-3334 KW - Butadienes KW - 0 KW - Carcinogens KW - Codon KW - DNA, Neoplasm KW - Hemiterpenes KW - Pentanes KW - isoprene KW - 0A62964IBU KW - Chloroprene KW - 126-99-8 KW - 1,3-butadiene KW - JSD5FGP5VD KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - DNA Mutational Analysis KW - Organ Specificity KW - Mice KW - Administration, Inhalation KW - Polymorphism, Single-Stranded Conformational KW - Male KW - Female KW - Structure-Activity Relationship KW - Carcinogens -- administration & dosage KW - Codon -- genetics KW - Carcinogens -- toxicity KW - Harderian Gland -- chemistry KW - Chloroprene -- administration & dosage KW - Genes, ras KW - Butadienes -- toxicity KW - Adenoma -- chemically induced KW - Point Mutation KW - Lung Neoplasms -- genetics KW - DNA, Neoplasm -- genetics KW - Butadienes -- administration & dosage KW - Chloroprene -- toxicity KW - Lung Neoplasms -- chemically induced KW - Harderian Gland -- drug effects KW - Sebaceous Gland Neoplasms -- genetics KW - Adenoma -- genetics KW - Sebaceous Gland Neoplasms -- chemically induced KW - Carcinoma -- chemically induced KW - Carcinoma -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69719954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=High+frequency+of+codon+61+K-ras+A--%26gt%3BT+transversions+in+lung+and+Harderian+gland+neoplasms+of+B6C3F1+mice+exposed+to+chloroprene+%282-chloro-1%2C3-butadiene%29+for+2+years%2C+and+comparisons+with+the+structurally+related+chemicals+isoprene+and+1%2C3-butadiene.&rft.au=Sills%2C+R+C%3BHong%2C+H+L%3BMelnick%2C+R+L%3BBoorman%2C+G+A%3BDevereux%2C+T+R&rft.aulast=Sills&rft.aufirst=R&rft.date=1999-04-01&rft.volume=20&rft.issue=4&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential expression of prostaglandin endoperoxide H synthase-2 and formation of activated beta-catenin-LEF-1 transcription complex in mouse colonic epithelial cells contrasting in Apc. AN - 69719772; 10223208 AB - Mutations in Apc underlie the intestinal lesions in familial adenomatous polyposis and are found in >85% of sporadic colon cancers. They are frequently associated with overexpression of prostaglandin endoperoxide H synthase-2 (PGHS-2) in colonic adenomas. It has been suggested that Apc mutations are linked mechanistically to increased PGHS-2 expression by elevated nuclear accumulation of beta-catenin-Tcf-LEF transcription complex. In the present study, we show that PGHS-2 is differentially expressed in mouse colonic epithelial cells with distinct Apc status. Cells with a mutated Apc expressed markedly higher levels of PGHS-2 mRNA and protein and produced significantly more prostaglandin E2 than cells with normal Apc. Using electrophoretic mobility shift assays, we demonstrate that DNA-beta-catenin-LEF-1 complex formation is differentially induced in these two cell lines in an Apc-dependent manner. Our data indicate that the differential induction of beta-catenin-LEF-1 complex correlates closely with differential expression of PGHS-2. These findings support the hypothesis that the differential expression of PGHS-2 is mediated through the proposed beta-catenin/Tcf-LEF signaling pathway. JF - Carcinogenesis AU - Mei, J M AU - Hord, N G AU - Winterstein, D F AU - Donald, S P AU - Phang, J M AD - Laboratory of Nutritional and Molecular Regulation, Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 737 EP - 740 VL - 20 IS - 4 SN - 0143-3334, 0143-3334 KW - Antigens, Polyomavirus Transforming KW - 0 KW - CTNNB1 protein, mouse KW - Cytoskeletal Proteins KW - DNA-Binding Proteins KW - Isoenzymes KW - Lymphoid Enhancer-Binding Factor 1 KW - Macromolecular Substances KW - Oligonucleotides KW - RNA, Messenger KW - Trans-Activators KW - Transcription Factors KW - beta Catenin KW - DNA KW - 9007-49-2 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - Prostaglandin-Endoperoxide Synthases KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Animals KW - Dinoprostone -- biosynthesis KW - Cell Nucleus -- metabolism KW - Antigens, Polyomavirus Transforming -- physiology KW - Oligonucleotides -- metabolism KW - RNA, Messenger -- genetics KW - RNA, Messenger -- biosynthesis KW - Epithelial Cells -- metabolism KW - Alleles KW - Binding, Competitive KW - Cell Line, Transformed KW - DNA -- metabolism KW - Simian virus 40 -- genetics KW - Temperature KW - Mice KW - Antigens, Polyomavirus Transforming -- genetics KW - Mice, Mutant Strains KW - DNA -- genetics KW - Crosses, Genetic KW - Enzyme Induction KW - Cell Transformation, Viral KW - Cell Line KW - Transcription Factors -- metabolism KW - Isoenzymes -- biosynthesis KW - Colon -- metabolism KW - Colon -- cytology KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Cytoskeletal Proteins -- metabolism KW - Isoenzymes -- genetics KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Genes, APC KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69719772?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=Differential+expression+of+prostaglandin+endoperoxide+H+synthase-2+and+formation+of+activated+beta-catenin-LEF-1+transcription+complex+in+mouse+colonic+epithelial+cells+contrasting+in+Apc.&rft.au=Mei%2C+J+M%3BHord%2C+N+G%3BWinterstein%2C+D+F%3BDonald%2C+S+P%3BPhang%2C+J+M&rft.aulast=Mei&rft.aufirst=J&rft.date=1999-04-01&rft.volume=20&rft.issue=4&rft.spage=737&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reactions of dihydrodiol epoxides of 5-methylchrysene and 5, 6-dimethylchrysene with DNA and deoxyribonucleotides. AN - 69708684; 10207124 AB - Both syn and anti dihydrodiol epoxides from 5-methylchrysene (5-MCDE) and 5,6-dimethylchrysene (5,6-DMCDE) were reacted under the same conditions with native DNA, denatured DNA, and purine deoxyribonucleotides, and the products were quantified. The extents of reaction with the deoxyribonucleotides were consistently greater for 5,6-DMCDE than for 5-MCDE. The yield of adducts in the reaction with DNA ranged from being a few-fold to 50-fold greater than those found in the corresponding deoxyribonucleotide reactions for both 5-MCDE and 5,6-DMCDE. The DNA-dependent enhancement of product yield was greater for 5-MCDE than for 5,6-DMCDE with a few exceptions among cis and trans deoxyadenosine adducts. The most substantial differences in DNA-dependent enhancement were found for deoxyguanosine adducts; thus, steric hindrance between the 6-methyl group in the 5,6-DMCDE and the minor groove in the DNA double helix may account for the greater DNA-dependent enhancement found in the 5-MCDE reactions. JF - Chemical research in toxicology AU - Szeliga, J AU - Amin, S AU - Zhang, F J AU - Harvey, R G AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 347 EP - 352 VL - 12 IS - 4 SN - 0893-228X, 0893-228X KW - Carcinogens KW - 0 KW - Chrysenes KW - DNA Adducts KW - Deoxyribonucleotides KW - 5,6-dimethylchrysene KW - 3697-27-6 KW - DNA KW - 9007-49-2 KW - 5-methylchrysene KW - O66195MC8L KW - Index Medicus KW - Structure-Activity Relationship KW - Carcinogens -- metabolism KW - DNA -- metabolism KW - Deoxyribonucleotides -- metabolism KW - Chrysenes -- metabolism KW - DNA Adducts -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69708684?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+research+in+toxicology&rft.atitle=Reactions+of+dihydrodiol+epoxides+of+5-methylchrysene+and+5%2C+6-dimethylchrysene+with+DNA+and+deoxyribonucleotides.&rft.au=Szeliga%2C+J%3BAmin%2C+S%3BZhang%2C+F+J%3BHarvey%2C+R+G&rft.aulast=Szeliga&rft.aufirst=J&rft.date=1999-04-01&rft.volume=12&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Chemical+research+in+toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-11 N1 - Date created - 1999-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reversal of doxorubicin-induced cardiac metabolic damage by L-carnitine. AN - 69705716; 10208759 AB - Biopharmacological evaluations of the protective effects of L-carnitine (a naturally occurring quaternary ammonium compound) against doxorubicin-induced metabolic damage were carried out in isolated cardiac myocytes and in isolated rat heart mitochondria. Perfusion of the heart with DOX (0.5 mM) caused a significant 70% inhibition of palmitate oxidation in cardiac myocytes, while L-carnitine (5 mM) perfusion caused stimulation which accounted for 37%. Perfusion of the heart with L-carnitine after 10-min perfusion with DOX (0.5 mM) caused 88% reversal of DOX-induced inhibition of palmitate oxidation in cardiac cells. In rat heart mitochondria, DOX has no effect on either palmitate oxidation or acyl-CoA synthetase activity, whereas Enoximone (c-AMP-dependent phosphodiesterase inhibitor), caused a significant inhibition of palmitate oxidation and acyl-CoA activity (40 and 27%, respectively). The oxidation of palmitoyl-CoA, an index of carnitine palmitoyltransferse reaction was significantly inhibited by DOX as a function of DOX concentration. Preincubation of mitochondria with L-carnitine caused reversal of DOX-induced inhibition of palmitoyl-CoA oxidation depending on the concentration of L-carnitine. Moreover, L-carnitine treatment did not interfere with the cytotoxic effect of doxorubicin against the growth of solid Ehrlich carcinoma. The findings of this study may suggest that inhibition of fatty acid oxidation in the heart is at least a part of doxorubicin cardiotoxicity and that L-carnitine can be used to prevent the doxorubcin-induced cardiac metabolic damage without interfering with its antitumour activities. Copyright 1999 The Italian Pharmacological Society. JF - Pharmacological research AU - Sayed-Ahmed, M M AU - Shaarawy, S AU - Shouman, S A AU - Osman, A M AD - Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 289 EP - 295 VL - 39 IS - 4 SN - 1043-6618, 1043-6618 KW - Antineoplastic Agents KW - 0 KW - Palmitic Acid KW - 2V16EO95H1 KW - Doxorubicin KW - 80168379AG KW - Carnitine KW - S7UI8SM58A KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Carcinoma, Ehrlich Tumor -- drug therapy KW - Carcinoma, Ehrlich Tumor -- pathology KW - Cell Division -- drug effects KW - Mice KW - Palmitic Acid -- metabolism KW - Rats KW - Oxidation-Reduction KW - Rats, Sprague-Dawley KW - Cells, Cultured KW - In Vitro Techniques KW - Female KW - Male KW - Cardiomyopathies -- metabolism KW - Doxorubicin -- pharmacology KW - Doxorubicin -- antagonists & inhibitors KW - Carnitine -- pharmacology KW - Cardiomyopathies -- drug therapy KW - Antineoplastic Agents -- toxicity KW - Doxorubicin -- toxicity KW - Cardiomyopathies -- chemically induced KW - Antineoplastic Agents -- pharmacology KW - Antineoplastic Agents -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69705716?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pharmacological+research&rft.atitle=Reversal+of+doxorubicin-induced+cardiac+metabolic+damage+by+L-carnitine.&rft.au=Sayed-Ahmed%2C+M+M%3BShaarawy%2C+S%3BShouman%2C+S+A%3BOsman%2C+A+M&rft.aulast=Sayed-Ahmed&rft.aufirst=M&rft.date=1999-04-01&rft.volume=39&rft.issue=4&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Pharmacological+research&rft.issn=10436618&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-15 N1 - Date created - 1999-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High prevalence of antibodies against HERV-K10 in patients with testicular cancer but not with AIDS. AN - 69702585; 10207631 AB - Human endogenous retrovirus K10 (HERV-K10) env and gag expression has been detected in placenta, embryonic tissue, and cell lines. By transfection, these sequences have been expressed in insect cells and developed into serological assays, revealing HERV-K10 antibodies in patients with testicular cancer. Patients with AIDS are at an increased risk for testicular cancer and frequently reactivate latent infections. We postulated that HERV-K10 seroprevalence might be increased with HIV infection or AIDS. Stored, frozen serum samples from 52 patients with testicular cancer (8 patients with HIV and 30 patients with samples near the time of diagnosis) and 84 controls (40 patients with HIV) were diluted 1:40 and tested by immunofluorescence against SF158 cells transfected with HERV-K10 env [ENV1.9(+)] or gag (pACGAG). Seroprevalence rates were compared cross-sectionally in cases and controls, excluding those with indeterminate results (3 of 30 cases and 7 of 84 controls), and also were examined longitudinally in the cases before or after diagnosis of testicular cancer. Seroprevalence to HERV-K10 Env or Gag was 17 of 27 testicular cancer patients (63%) around the time of diagnosis, compared to 4 of 77 controls (5%; P < 0.0001). Seroprevalence was similar (50% to 60%) with seminoma, teratocarcinoma, or embryonal carcinoma, and it was not increased with HIV infection in either cases (33%) or controls (3%). HERV-K10 antibodies were detected in 12 of 19 cases (63%) more than 6 months before seminoma diagnosis, as well as in four cases with residual or recurrent malignancy more than 1 month after initial diagnosis. Thus, HERV-K10 antibodies are detected frequently with testicular cancer and seem to resolve rapidly with effective therapy of the malignancy. Antibody reactivity also occurs in approximately 5% of controls, perhaps because of nonspecific or cross-reactive epitopes. HIV and AIDS were not associated with HERV-K10 antibodies, thus, leaving their higher risk of testicular cancer unexplained. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Goedert, J J AU - Sauter, M E AU - Jacobson, L P AU - Vessella, R L AU - Hilgartner, M W AU - Leitman, S F AU - Fraser, M C AU - Mueller-Lantzsch, N G AD - Viral Epidemiology Branch, National Cancer Institute, Rockville, Maryland 20852, USA. goedertj@mail.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 293 EP - 296 VL - 8 IS - 4 Pt 1 SN - 1055-9965, 1055-9965 KW - Antibodies, Viral KW - 0 KW - Gene Products, gag KW - HIV Antibodies KW - Index Medicus KW - AIDS/HIV KW - Sensitivity and Specificity KW - Humans KW - Seroepidemiologic Studies KW - Aged KW - Risk Assessment KW - Cross-Sectional Studies KW - HIV Infections -- immunology KW - Adult KW - Case-Control Studies KW - HIV Antibodies -- analysis KW - HIV Infections -- genetics KW - Middle Aged KW - Fluorescent Antibody Technique KW - HIV Infections -- epidemiology KW - Male KW - Gene Products, gag -- genetics KW - Seminoma -- immunology KW - Retroviridae -- immunology KW - Acquired Immunodeficiency Syndrome -- epidemiology KW - Seminoma -- genetics KW - Acquired Immunodeficiency Syndrome -- immunology KW - Testicular Neoplasms -- immunology KW - Gene Products, gag -- immunology KW - Seminoma -- epidemiology KW - Retroviridae -- genetics KW - Testicular Neoplasms -- genetics KW - Testicular Neoplasms -- epidemiology KW - Antibodies, Viral -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69702585?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=High+prevalence+of+antibodies+against+HERV-K10+in+patients+with+testicular+cancer+but+not+with+AIDS.&rft.au=Goedert%2C+J+J%3BSauter%2C+M+E%3BJacobson%2C+L+P%3BVessella%2C+R+L%3BHilgartner%2C+M+W%3BLeitman%2C+S+F%3BFraser%2C+M+C%3BMueller-Lantzsch%2C+N+G&rft.aulast=Goedert&rft.aufirst=J&rft.date=1999-04-01&rft.volume=8&rft.issue=4+Pt+1&rft.spage=293&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-17 N1 - Date created - 1999-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K(alpha) and pandinustoxin-K(alpha). AN - 69701643; 10210033 AB - The scorpion venom peptide toxins tityustoxin-K(alpha) (TsTx-K(alpha)) and pandinustoxin-K(alpha) (PiTx-K(alpha)) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K(alpha) preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K(alpha) is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists 4-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca(2+)-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K(alpha) and PiTx-K(alpha) in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K(alpha) and PiTx-K(alpha) were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 microg. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca(2+)-activated K+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors. JF - Epilepsy research AU - Juhng, K N AU - Kokate, T G AU - Yamaguchi, S AU - Kim, B Y AU - Rogowski, R S AU - Blaustein, M P AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 177 EP - 186 VL - 34 IS - 2-3 SN - 0920-1211, 0920-1211 KW - Anti-Anxiety Agents KW - 0 KW - Anticonvulsants KW - Excitatory Amino Acid Antagonists KW - Neuroprotective Agents KW - Pandinus toxin K-alpha KW - Potassium Channel Blockers KW - Scorpion Venoms KW - GYKI 52466 KW - 102771-26-6 KW - Benzodiazepines KW - 12794-10-4 KW - Carbamazepine KW - 33CM23913M KW - tityustoxin KW - 39465-37-7 KW - Phenytoin KW - 6158TKW0C5 KW - Dizocilpine Maleate KW - 6LR8C1B66Q KW - 4-Aminopyridine KW - BH3B64OKL9 KW - Index Medicus KW - Animals KW - Electroencephalography KW - 4-Aminopyridine -- antagonists & inhibitors KW - Mice KW - Scorpion Venoms -- administration & dosage KW - Neuroprotective Agents -- pharmacology KW - Dizocilpine Maleate -- pharmacology KW - Excitatory Amino Acid Antagonists -- pharmacology KW - Injections, Intraventricular KW - Anti-Anxiety Agents -- pharmacology KW - Anticonvulsants -- pharmacology KW - Phenytoin -- pharmacology KW - Carbamazepine -- pharmacology KW - Scorpion Venoms -- antagonists & inhibitors KW - 4-Aminopyridine -- administration & dosage KW - Male KW - Seizures -- chemically induced KW - Seizures -- physiopathology KW - Seizures -- prevention & control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69701643?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Epilepsy+research&rft.atitle=Induction+of+seizures+by+the+potent+K%2B+channel-blocking+scorpion+venom+peptide+toxins+tityustoxin-K%28alpha%29+and+pandinustoxin-K%28alpha%29.&rft.au=Juhng%2C+K+N%3BKokate%2C+T+G%3BYamaguchi%2C+S%3BKim%2C+B+Y%3BRogowski%2C+R+S%3BBlaustein%2C+M+P%3BRogawski%2C+M+A&rft.aulast=Juhng&rft.aufirst=K&rft.date=1999-04-01&rft.volume=34&rft.issue=2-3&rft.spage=177&rft.isbn=&rft.btitle=&rft.title=Epilepsy+research&rft.issn=09201211&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-17 N1 - Date created - 1999-06-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells. AN - 69687791; 10198357 AB - Our laboratory has recently shown that mucus differentiation of cultured normal human tracheobronchial epithelial (NHTBE) cells is accompanied by the increased expression of 15-lipoxygenase (15-LO). We used differentiated NHTBE cells to investigate the regulation of 15-LO expression and mucus secretion by inflammatory cytokines. Interleukin (IL)-4 and IL-13 dramatically enhanced the expression of 15-LO, whereas tumor necrosis factor-alpha, IL-1beta, and interferon (IFN)-gamma had no effect. These cytokines did not increase the expression of cyclooxygenase-2, with the exception of a modest induction by IL-1beta. The IL-4-induced 15-LO expression was concentration dependent, and mRNA and protein expression increased within 3 and 6 h, respectively, after IL-4 treatment. In metabolism studies with intact cells, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) were the major metabolites formed from exogenous arachidonic acid and linoleic acid. No prostaglandins were detected. IL-4 treatment dramatically increased the formation of 13-HODE and 15-HETE compared with that in untreated NHTBE cells, and several additional 15-LO metabolites were observed. Pretreatment of NHTBE cells with IFN-gamma or dexamethasone did not inhibit the IL-4-induced expression of 15-LO except at high concentrations (100 ng/ml of IFN-gamma and 10 microM dexamethasone). IL-4 treatment inhibited mucus secretion and attenuated the expression of the mucin genes MUC5AC and MUC5B at 12-24 h after treatment. Addition of 15-HETE precursor and 13-HODE precursor to the cultures did not alter mucin secretion or mucin gene expression. On the basis of the data presented, we conclude that the increase in 15-LO expression by IL-4 and attenuation of mucus secretion may be independent biological events. JF - The American journal of physiology AU - Jayawickreme, S P AU - Gray, T AU - Nettesheim, P AU - Eling, T AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - L596 EP - L603 VL - 276 IS - 4 Pt 1 SN - 0002-9513, 0002-9513 KW - Interleukin-1 KW - 0 KW - Interleukin-13 KW - Isoenzymes KW - Membrane Proteins KW - Tumor Necrosis Factor-alpha KW - Interleukin-4 KW - 207137-56-2 KW - Arachidonic Acid KW - 27YG812J1I KW - Interferon-gamma KW - 82115-62-6 KW - Linoleic Acid KW - 9KJL21T0QJ KW - Arachidonate 15-Lipoxygenase KW - EC 1.13.11.33 KW - Cyclooxygenase 2 KW - EC 1.14.99.1 KW - PTGS2 protein, human KW - Prostaglandin-Endoperoxide Synthases KW - Index Medicus KW - Interleukin-1 -- pharmacology KW - Linoleic Acid -- metabolism KW - Humans KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Interferon-gamma -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Isoenzymes -- genetics KW - Arachidonic Acid -- metabolism KW - Interleukin-13 -- pharmacology KW - Isoenzymes -- biosynthesis KW - Enzyme Induction KW - Prostaglandin-Endoperoxide Synthases -- genetics KW - Prostaglandin-Endoperoxide Synthases -- biosynthesis KW - Cell Line KW - Epithelial Cells -- physiology KW - Gene Expression Regulation, Enzymologic KW - Epithelial Cells -- drug effects KW - Arachidonate 15-Lipoxygenase -- biosynthesis KW - Arachidonate 15-Lipoxygenase -- genetics KW - Interleukin-4 -- pharmacology KW - Epithelial Cells -- immunology KW - Bronchi -- drug effects KW - Bronchi -- physiology KW - Bronchi -- immunology KW - Mucus -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69687791?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Regulation+of+15-lipoxygenase+expression+and+mucus+secretion+by+IL-4+in+human+bronchial+epithelial+cells.&rft.au=Jayawickreme%2C+S+P%3BGray%2C+T%3BNettesheim%2C+P%3BEling%2C+T&rft.aulast=Jayawickreme&rft.aufirst=S&rft.date=1999-04-01&rft.volume=276&rft.issue=4+Pt+1&rft.spage=L596&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-18 N1 - Date created - 1999-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of oral zidovudine entrapped in biodegradable nanospheres in rabbits. AN - 69685908; 10103214 AB - The pharmacokinetic profile of oral zidovudine entrapped in a 50:50 polyactide-coglycolide matrix (nanospheres) was compared to those of standard oral and parenteral zidovudine formulations in rabbits. The bioavailability of zidovudine nanospheres at 50 mg/kg of body weight was 76%, and this dose achieved prolonged exposure to zidovudine compared to standard formulations without an increase in the drug's peak concentration. JF - Antimicrobial agents and chemotherapy AU - Callender, D P AU - Jayaprakash, N AU - Bell, A AU - Petraitis, V AU - Petraitiene, R AU - Candelario, M AU - Schaufele, R AU - Dunn, J M AU - Sei, S AU - Walsh, T J AU - Balis, F M AU - Petratienes, R AD - Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 972 EP - 974 VL - 43 IS - 4 SN - 0066-4804, 0066-4804 KW - Anti-HIV Agents KW - 0 KW - Drug Carriers KW - Zidovudine KW - 4B9XT59T7S KW - Index Medicus KW - AIDS/HIV KW - Body Weight KW - Animals KW - Anti-HIV Agents -- pharmacokinetics KW - Area Under Curve KW - Anti-HIV Agents -- administration & dosage KW - Rabbits KW - Biodegradation, Environmental KW - Microspheres KW - Zidovudine -- pharmacokinetics KW - Zidovudine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69685908?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=Pharmacokinetics+of+oral+zidovudine+entrapped+in+biodegradable+nanospheres+in+rabbits.&rft.au=Callender%2C+D+P%3BJayaprakash%2C+N%3BBell%2C+A%3BPetraitis%2C+V%3BPetraitiene%2C+R%3BCandelario%2C+M%3BSchaufele%2C+R%3BDunn%2C+J+M%3BSei%2C+S%3BWalsh%2C+T+J%3BBalis%2C+F+M%3BPetratienes%2C+R&rft.aulast=Callender&rft.aufirst=D&rft.date=1999-04-01&rft.volume=43&rft.issue=4&rft.spage=972&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-03 N1 - Date created - 1999-06-03 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Lab Anim Sci. 1988 Aug;38(4):467-71 [3184859] Ann Intern Med. 1989 Feb 15;110(4):279-85 [2643914] J Pediatr. 1989 May;114(5):880-4 [2715903] J Pharm Sci. 1996 Feb;85(2):144-9 [8683438] J Pharm Sci. 1982 Mar;71(3):372-3 [7069605] AIDS. 1996 Oct;10(12):1361-7 [8902065] Clin Pharmacokinet. 1996 Apr;30(4):251-62 [8983858] J Pharm Sci. 1997 May;86(5):554-9 [9145378] J Microencapsul. 1996 May-Jun;13(3):257-67 [8860682] Erratum In: Antimicrob Agents Chemother 1999 Dec;43(12):3046 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Organic cation transport in rat choroid plexus cells studied by fluorescence microscopy. AN - 69684461; 10199828 AB - Quinacrine uptake and distribution were studied in a primary culture of rat choroid plexus epithelial cells using conventional and confocal fluorescence microscopy and image analysis. Quinacrine rapidly accumulated in cells, with steady-state levels being achieved after 10-20 min. Uptake was reduced by other organic cations, e.g., tetraethylammonium (TEA), and by KCN. Quinacrine fluorescence was distributed in two cytoplasmic compartments, one diffuse and the other punctate. TEA efflux experiments indicated that more than one-half of intracellular organic cation was in a slowly emptying compartment. The protonophore monensin both emptied that TEA compartment and abolished punctate quinacrine fluorescence, suggesting that a large fraction of total intracellular organic cation was sequestered in acidic vesicles, e.g., endosomes. Finally, quinacrine-loaded vesicles were seen to move within the cytoplasm and to abruptly release their contents at the blood side of the cell; the rate of release was greatly reduced by the microtubule disrupter nocodazole. JF - The American journal of physiology AU - Miller, D S AU - Villalobos, A R AU - Pritchard, J B AD - Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. miller@niehs.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - C955 EP - C968 VL - 276 IS - 4 Pt 1 SN - 0002-9513, 0002-9513 KW - Cations KW - 0 KW - Tetraethylammonium KW - 66-40-0 KW - Monensin KW - 906O0YJ6ZP KW - Verapamil KW - CJ0O37KU29 KW - Quinacrine KW - H0C805XYDE KW - Potassium Cyanide KW - MQD255M2ZO KW - Index Medicus KW - Animals KW - Video Recording KW - Monensin -- pharmacology KW - Verapamil -- pharmacology KW - Potassium Cyanide -- pharmacology KW - Biological Transport -- drug effects KW - Rats KW - Animals, Newborn KW - Rats, Inbred F344 KW - Kinetics KW - Microscopy, Fluorescence -- methods KW - Microscopy, Confocal -- methods KW - Quinacrine -- pharmacokinetics KW - Tetraethylammonium -- pharmacology KW - Tetraethylammonium -- pharmacokinetics KW - Neurons -- drug effects KW - Neurons -- cytology KW - Neurons -- physiology KW - Choroid Plexus -- cytology KW - Choroid Plexus -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69684461?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+physiology&rft.atitle=Organic+cation+transport+in+rat+choroid+plexus+cells+studied+by+fluorescence+microscopy.&rft.au=Miller%2C+D+S%3BVillalobos%2C+A+R%3BPritchard%2C+J+B&rft.aulast=Miller&rft.aufirst=D&rft.date=1999-04-01&rft.volume=276&rft.issue=4+Pt+1&rft.spage=C955&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+physiology&rft.issn=00029513&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-18 N1 - Date created - 1999-05-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis. AN - 69683131; 10197298 AB - The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique. JF - Journal of clinical pharmacology AU - Cho, H K AU - Lush, R M AU - Bartlett, D L AU - Alexander, H R AU - Wu, P C AU - Libutti, S K AU - Lee, K B AU - Venzon, D J AU - Bauer, K S AU - Reed, E AU - Figg, W D AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 394 EP - 401 VL - 39 IS - 4 SN - 0091-2700, 0091-2700 KW - Antineoplastic Agents KW - 0 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Area Under Curve KW - Humans KW - Chemotherapy, Cancer, Regional Perfusion KW - Adult KW - Aged KW - Middle Aged KW - Cisplatin -- pharmacokinetics KW - Antineoplastic Agents -- pharmacokinetics KW - Hyperthermia, Induced KW - Cisplatin -- blood KW - Peritoneal Neoplasms -- therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69683131?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Pharmacokinetics+of+cisplatin+administered+by+continuous+hyperthermic+peritoneal+perfusion+%28CHPP%29+to+patients+with+peritoneal+carcinomatosis.&rft.au=Cho%2C+H+K%3BLush%2C+R+M%3BBartlett%2C+D+L%3BAlexander%2C+H+R%3BWu%2C+P+C%3BLibutti%2C+S+K%3BLee%2C+K+B%3BVenzon%2C+D+J%3BBauer%2C+K+S%3BReed%2C+E%3BFigg%2C+W+D&rft.aulast=Cho&rft.aufirst=H&rft.date=1999-04-01&rft.volume=39&rft.issue=4&rft.spage=394&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-23 N1 - Date created - 1999-06-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hippocampal volume in patients with alcohol dependence. AN - 69680833; 10197833 AB - Smaller hippocampal volumes have been reported in the brains of alcoholic patients than in those of healthy subjects, although it is unclear if the hippocampus is disproportionally smaller than the brain as a whole. There is evidence that alcoholic women are more susceptible than alcoholic men to liver and cardiac damage from alcohol. It is not known whether the hippocampi of the female brain are more vulnerable to alcohol. We compared the hippocampal volumes in 52 hospitalized alcoholic men and women with those of 36 healthy nonalcoholic men and women. All subjects were between 27 and 53 years of age. The hippocampal volumes were measured from sagittal T-weighted high-resolution magnetic resonance images. The alcoholic women had less lifetime drinking and a later age at onset of heavy drinking than alcoholic men. Both alcoholic men and women had significantly smaller right hippocampi and larger cerebrospinal fluid volumes than healthy subjects of the same sex. Only among women were the left hippocampus and the nonhippocampal brain volume also significantly smaller. The proportion of hippocampal volume relative to the rest of the brain volume was the same in alcoholic patients and healthy subjects, in both men and women. The right hippocampus was larger than the left among all subjects. Women demonstrated larger hippocampal volumes relative to total brain volume than men. Psychiatric comorbidity, including posttraumatic stress disorder, did not affect hippocampal volume. In chronic alcoholism, the reduction of hippocampal volume is proportional to the reduction of the brain volume. Alcohol consumption should be accounted for in studies of hippocampal damage. JF - Archives of general psychiatry AU - Agartz, I AU - Momenan, R AU - Rawlings, R R AU - Kerich, M J AU - Hommer, D W AD - Section on Electrophysiology and Brain Imaging, Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Ingrid.Agartz@knv.ki.se Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 356 EP - 363 VL - 56 IS - 4 SN - 0003-990X, 0003-990X KW - Abridged Index Medicus KW - Index Medicus KW - Sex Factors KW - Mental Disorders -- epidemiology KW - Humans KW - Adult KW - Alcohol Drinking -- psychology KW - Body Mass Index KW - Cerebrospinal Fluid -- physiology KW - Male KW - Functional Laterality KW - Female KW - Comorbidity KW - Magnetic Resonance Imaging KW - Alcoholism -- epidemiology KW - Alcoholism -- diagnosis KW - Alcoholism -- psychology KW - Hippocampus -- anatomy & histology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69680833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+general+psychiatry&rft.atitle=Hippocampal+volume+in+patients+with+alcohol+dependence.&rft.au=Agartz%2C+I%3BMomenan%2C+R%3BRawlings%2C+R+R%3BKerich%2C+M+J%3BHommer%2C+D+W&rft.aulast=Agartz&rft.aufirst=I&rft.date=1999-04-01&rft.volume=56&rft.issue=4&rft.spage=356&rft.isbn=&rft.btitle=&rft.title=Archives+of+general+psychiatry&rft.issn=0003990X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-14 N1 - Date created - 1999-04-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Control of action potential-driven calcium influx in GT1 neurons by the activation status of sodium and calcium channels. AN - 69679437; 10194765 AB - An analysis of the relationship between electrical membrane activity and Ca2+ influx in differentiated GnRH-secreting (GT1) neurons revealed that most cells exhibited spontaneous, extracellular Ca(2+)-dependent action potentials (APs). Spiking was initiated by a slow pacemaker depolarization from a baseline potential between -75 and -50 mV, and AP frequency increased with membrane depolarization. More hyperpolarized cells fired sharp APs with limited capacity to promote Ca2+ influx, whereas more depolarized cells fired broad APs with enhanced capacity for Ca2+ influx. Characterization of the inward currents in GT1 cells revealed the presence of tetrodotoxin-sensitive Na+, Ni(2+)-sensitive T-type Ca2+, and dihydropyridine-sensitive L-type Ca2+ components. The availability of Na+ and T-type Ca2+ channels was dependent on the baseline potential, which determined the activation/inactivation status of these channels. Whereas all three channels were involved in the generation of sharp APs, L-type channels were solely responsible for the spike depolarization in cells exhibiting broad APs. Activation of GnRH receptors led to biphasic changes in cytosolic Ca2+ concentration ([Ca2+]i), with an early, extracellular Ca(2+)-independent peak and a sustained, extracellular Ca(2+)-dependent phase. During the peak [Ca2+]i response, electrical activity was abolished due to transient hyperpolarization. This was followed by sustained depolarization of cells and resumption of firing of increased frequency with a shift from sharp to broad APs. The GnRH-induced change in firing pattern accounted for about 50% of the elevated Ca2+ influx, the remainder being independent of spiking. Basal [Ca2+]i was also dependent on Ca2+ influx through AP-driven and voltage-insensitive pathways. Thus, in both resting and agonist-stimulated GT1 cells, membrane depolarization limits the participation of Na+ and T-type channels in firing, but facilitates AP-driven Ca2+ influx. JF - Molecular endocrinology (Baltimore, Md.) AU - Van Goor, F AU - Krsmanovic, L Z AU - Catt, K J AU - Stojilkovic, S S AD - Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 587 EP - 603 VL - 13 IS - 4 SN - 0888-8809, 0888-8809 KW - Calcium Channel Agonists KW - 0 KW - Calcium Channel Blockers KW - Calcium Channels KW - Sodium Channels KW - Gonadotropin-Releasing Hormone KW - 33515-09-2 KW - Tetrodotoxin KW - 4368-28-9 KW - Tetraethylammonium KW - 66-40-0 KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester KW - 71145-03-4 KW - Nifedipine KW - I9ZF7L6G2L KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Tetraethylammonium -- pharmacology KW - 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester -- pharmacology KW - Mice KW - Electrophysiology KW - Calcium Channel Agonists -- pharmacology KW - Nifedipine -- pharmacology KW - Gonadotropin-Releasing Hormone -- metabolism KW - Calcium Channel Blockers -- pharmacology KW - Hypothalamus -- metabolism KW - Cell Membrane -- metabolism KW - Tetrodotoxin -- pharmacology KW - Calcium Signaling KW - Calcium -- metabolism KW - Action Potentials -- physiology KW - Calcium Channels -- metabolism KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Calcium Channels -- drug effects KW - Sodium Channels -- metabolism KW - Action Potentials -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69679437?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Control+of+action+potential-driven+calcium+influx+in+GT1+neurons+by+the+activation+status+of+sodium+and+calcium+channels.&rft.au=Van+Goor%2C+F%3BKrsmanovic%2C+L+Z%3BCatt%2C+K+J%3BStojilkovic%2C+S+S&rft.aulast=Van+Goor&rft.aufirst=F&rft.date=1999-04-01&rft.volume=13&rft.issue=4&rft.spage=587&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-27 N1 - Date created - 1999-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor. AN - 69679026; 10194759 AB - Sorting of the prohormone POMC to the regulated secretory pathway necessitates the binding of a sorting signal to a sorting receptor, identified as membrane carboxypeptidase E (CPE). The sorting signal, located at the N terminus of POMC consists of two acidic (Asp10, Glu14) and two hydrophobic (Leu11, Leu18) residues exposed on the surface of an amphipathic loop. In this study, molecular modeling of CPE predicted that the acidic residues in the POMC-sorting signal bind specifically to two basic residues, Arg255 and Lys260, present in a loop unique to CPE, compared with other carboxypeptidases. To test the model, these two residues on CPE were mutated to Ser or Ala, followed by baculovirus expression of the mutant CPEs in Sf9 cells. Sf9 cell membranes containing CPE mutants with either Arg255 or Lys260, or both residues substituted, showed no binding of [125I]N-POMC1-26 (which contains the POMC-sorting signal motif), proinsulin, or proenkephalin. In contrast, substitution of an Arg147 to Ala147 at a substrate-binding site, Arg259 to Ala259 and Ser202 to Pro202, in CPE did not affect the level of [125I]N-POMC1-26 binding when compared with-wild type CPE. Furthermore, mutation of the POMC-sorting signal motif (Asp10, Leu11, Glu14, Leu18) eliminated binding to wild-type CPE. These results indicate that the sorting signal of POMC, proinsulin, and proenkephalin specifically interacts with Arg255 and Lys260 at a novel binding site, independent of the active site on CPE. JF - Molecular endocrinology (Baltimore, Md.) AU - Zhang, C F AU - Snell, C R AU - Loh, Y P AD - Section on Cellular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 527 EP - 536 VL - 13 IS - 4 SN - 0888-8809, 0888-8809 KW - Enkephalins KW - 0 KW - Peptide Fragments KW - Protein Precursors KW - Recombinant Proteins KW - proenkephalin KW - Pro-Opiomelanocortin KW - 66796-54-1 KW - Proinsulin KW - 9035-68-1 KW - Arginine KW - 94ZLA3W45F KW - Carboxypeptidases KW - EC 3.4.- KW - Carboxypeptidase H KW - EC 3.4.17.10 KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Peptide Fragments -- metabolism KW - Animals KW - Protein Precursors -- metabolism KW - Arginine -- metabolism KW - Proinsulin -- metabolism KW - Models, Molecular KW - Recombinant Proteins -- genetics KW - Lysine -- metabolism KW - Binding Sites KW - Mutagenesis, Site-Directed KW - Baculoviridae -- genetics KW - Insects -- cytology KW - Recombinant Proteins -- metabolism KW - Insects -- virology KW - Enkephalins -- metabolism KW - Recombinant Proteins -- chemistry KW - Cell Membrane -- metabolism KW - Mutation KW - Protein Conformation KW - Carboxypeptidases -- genetics KW - Carboxypeptidases -- metabolism KW - Carboxypeptidases -- chemistry KW - Signal Transduction KW - Pro-Opiomelanocortin -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69679026?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.atitle=Identification+of+a+novel+prohormone+sorting+signal-binding+site+on+carboxypeptidase+E%2C+a+regulated+secretory+pathway-sorting+receptor.&rft.au=Zhang%2C+C+F%3BSnell%2C+C+R%3BLoh%2C+Y+P&rft.aulast=Zhang&rft.aufirst=C&rft.date=1999-04-01&rft.volume=13&rft.issue=4&rft.spage=527&rft.isbn=&rft.btitle=&rft.title=Molecular+endocrinology+%28Baltimore%2C+Md.%29&rft.issn=08888809&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-27 N1 - Date created - 1999-05-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective effect of the type IV phosphodiesterase inhibitor rolipram in EAU: protection is independent of IL-10-inducing activity. AN - 69663603; 10102291 AB - Experimental autoimmune uveoretinitis (EAU) is a cell-mediated model of retinal autoimmunity that is negatively regulated by interleukin (IL)-10. The antidepressant drug rolipram, a type IV phosphodiesterase inhibitor, enhances IL-10 production by monocyte/macrophages. The effect of rolipram on induction of EAU and its associated immunologic responses was investigated. Mice were challenged for EAU induction by immunization with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of uveitogenic T cells and were treated with rolipram. EAU severity and immunologic responses to IRBP were analyzed. In addition, the effect of rolipram added to the culture on antigen-driven responses of primed lymph node cells was tested. Rolipram treatment from days -1 to 7 after immunization (afferent phase) was not protective, but severity of EAU was reduced to 50% by treatment from days 8 to 16 after immunization or when EAU was induced by adoptive transfer (efferent phase). Antigen-specific proliferation and interferon (IFN)-gamma production ex vivo by lymph node cells of protected mice were not reduced. However, the addition of rolipram directly to the culture suppressed IRBP-driven proliferation and IFN-gamma production by primed lymph node cells. Freshly explanted lymph node cells of treated mice showed inhibition of IFN-gamma mRNA but no parallel enhancement of IL-10 mRNA by quantitative polymerase chain reaction. Rolipram inhibited EAU in IL-10 knockout mice equally well compared with controls and suppressed their primed lymph node cells in culture. Rolipram appears to inhibit the expansion and effector function of uveitogenic T cells, raising the possibility that it may be useful for treatment of established disease. Contrary to expectations based on in vitro studies, the protective effects in vivo appear to be independent of IL-10. The observation that suppression of antigen-specific responses is demonstrable only in the physical presence of the drug suggests that, in a clinical setting, continuous administration of rolipram might be needed to sustain its therapeutic effect. JF - Investigative ophthalmology & visual science AU - Xu, H AU - Strassmann, G AU - Chan, C C AU - Rizzo, L V AU - Silver, P B AU - Wiggert, B AU - Caspi, R R AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1858, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 942 EP - 950 VL - 40 IS - 5 SN - 0146-0404, 0146-0404 KW - DNA Primers KW - 0 KW - Eye Proteins KW - Phosphodiesterase Inhibitors KW - Pyrrolidinones KW - RNA, Messenger KW - Retinol-Binding Proteins KW - interstitial retinol-binding protein KW - Interleukin-10 KW - 130068-27-8 KW - Interferon-gamma KW - 82115-62-6 KW - Rolipram KW - K676NL63N7 KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Interferon-gamma -- biosynthesis KW - Mice KW - Reverse Transcriptase Polymerase Chain Reaction KW - Macrophages -- drug effects KW - Lymph Nodes -- cytology KW - Hypersensitivity, Delayed -- immunology KW - Mice, Knockout KW - Lymphocyte Activation -- drug effects KW - Adoptive Transfer KW - RNA, Messenger -- metabolism KW - Monocytes -- metabolism KW - Mice, Inbred C57BL KW - Monocytes -- drug effects KW - T-Lymphocytes -- drug effects KW - T-Lymphocytes -- immunology KW - Female KW - Male KW - DNA Primers -- chemistry KW - Macrophages -- metabolism KW - Uveitis -- prevention & control KW - Autoimmune Diseases -- prevention & control KW - Phosphodiesterase Inhibitors -- pharmacology KW - Uveitis -- pathology KW - Retinitis -- pathology KW - Retinitis -- prevention & control KW - Retinitis -- immunology KW - Uveitis -- immunology KW - Retinitis -- chemically induced KW - Interleukin-10 -- metabolism KW - Autoimmune Diseases -- pathology KW - Autoimmune Diseases -- chemically induced KW - Interleukin-10 -- genetics KW - Pyrrolidinones -- pharmacology KW - Uveitis -- chemically induced KW - Autoimmune Diseases -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69663603?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Investigative+ophthalmology+%26+visual+science&rft.atitle=Protective+effect+of+the+type+IV+phosphodiesterase+inhibitor+rolipram+in+EAU%3A+protection+is+independent+of+IL-10-inducing+activity.&rft.au=Xu%2C+H%3BStrassmann%2C+G%3BChan%2C+C+C%3BRizzo%2C+L+V%3BSilver%2C+P+B%3BWiggert%2C+B%3BCaspi%2C+R+R&rft.aulast=Xu&rft.aufirst=H&rft.date=1999-04-01&rft.volume=40&rft.issue=5&rft.spage=942&rft.isbn=&rft.btitle=&rft.title=Investigative+ophthalmology+%26+visual+science&rft.issn=01460404&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-02 N1 - Date created - 1999-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization. AN - 69656163; 10094966 AB - To search for recurrent and specific genomic alterations in human hepatocellular carcinoma (HCC), we examined 18 cell lines by comparative genomic hybridization (CGH), a molecular cytogenetic approach that allows positional identification of gains and losses of DNA sequences of the entire tumor genome. We report here a distinct pattern of multiple recurrent DNA copy-number gains and losses that include alterations frequently seen in other neoplasias as well as changes potentially specific for HCC. The most frequent gains were localized on 1p34.3-35, 1p33-34.1, 1q21-23, 1q31-32, 6p11-12, 7p21, 7q11.2, 8q24.1-24.2, 11q11-13, 12q11-13, 12q23, 17q11. 2-21, 17q23-24, and 20p11.1-q13.2. Recurrent losses were mapped on 3p12-14, 3q25, 4p12-14, 4q13-34, 5q21, 6q25-26, 8p11.2-23, 9p12-24, 11q23-24, 13q12-33, 14q12-13, 15q25-26, 18q11.2-22.2, and 21q21-22. Seventeen genomic imbalances are novel in HCC, thus extending significantly the map of genetic changes and providing a starting point for the isolation of new genes relevant in pathogenesis of liver neoplasia, as well as providing molecular probes for both diagnosis and monitoring treatment of the disease. JF - Hepatology (Baltimore, Md.) AU - Zimonjic, D B AU - Keck, C L AU - Thorgeirsson, S S AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1208 EP - 1214 VL - 29 IS - 4 SN - 0270-9139, 0270-9139 KW - Index Medicus KW - Karyotyping KW - Tumor Cells, Cultured KW - Humans KW - In Situ Hybridization, Fluorescence KW - Nucleic Acid Hybridization KW - Chromosome Mapping KW - Chromosomes, Human -- genetics KW - Liver -- ultrastructure KW - Carcinoma, Hepatocellular -- genetics KW - Gene Dosage KW - Liver Neoplasms -- genetics KW - Gene Deletion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69656163?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Hepatology+%28Baltimore%2C+Md.%29&rft.atitle=Novel+recurrent+genetic+imbalances+in+human+hepatocellular+carcinoma+cell+lines+identified+by+comparative+genomic+hybridization.&rft.au=Zimonjic%2C+D+B%3BKeck%2C+C+L%3BThorgeirsson%2C+S+S%3BPopescu%2C+N+C&rft.aulast=Zimonjic&rft.aufirst=D&rft.date=1999-04-01&rft.volume=29&rft.issue=4&rft.spage=1208&rft.isbn=&rft.btitle=&rft.title=Hepatology+%28Baltimore%2C+Md.%29&rft.issn=02709139&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-20 N1 - Date created - 1999-05-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers. AN - 69655833; 10098872 AB - Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), may depend on plasma concentrations of the essential amino acid L-tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36-h CSF collection via lumbar drain. Six subjects who were in good health were put on a low-TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP-deficient 15-amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5-HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at approximately 2 h following ingestion of the TRP-free amino acid drink and were lowest approximately 6 h after ATD; CSF TRP and 5-HIAA were decreased at 2.5 h and approximately 4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5-HIAA continued to decrease 14 h after the TRP-deficient amino acid drink was given. JF - Journal of neurochemistry AU - Williams, W A AU - Shoaf, S E AU - Hommer, D AU - Rawlings, R AU - Linnoila, M AD - National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical Studies, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1641 EP - 1647 VL - 72 IS - 4 SN - 0022-3042, 0022-3042 KW - Amino Acids KW - 0 KW - Serotonin KW - 333DO1RDJY KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Tryptophan KW - 8DUH1N11BX KW - Index Medicus KW - Amino Acids -- administration & dosage KW - Serotonin -- biosynthesis KW - Humans KW - Adult KW - Alcoholism -- metabolism KW - Middle Aged KW - Brain -- metabolism KW - Diet KW - Male KW - Female KW - Hydroxyindoleacetic Acid -- blood KW - Brain Chemistry -- drug effects KW - Tryptophan -- cerebrospinal fluid KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Tryptophan -- deficiency KW - Tryptophan -- blood KW - Brain Chemistry -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69655833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurochemistry&rft.atitle=Effects+of+acute+tryptophan+depletion+on+plasma+and+cerebrospinal+fluid+tryptophan+and+5-hydroxyindoleacetic+acid+in+normal+volunteers.&rft.au=Williams%2C+W+A%3BShoaf%2C+S+E%3BHommer%2C+D%3BRawlings%2C+R%3BLinnoila%2C+M&rft.aulast=Williams&rft.aufirst=W&rft.date=1999-04-01&rft.volume=72&rft.issue=4&rft.spage=1641&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurochemistry&rft.issn=00223042&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity. AN - 69638786; 10087053 AB - The purpose of this study was to examine whether intracellular metallothionein (MT) protects against acetaminophen hepatotoxicity. MT-I/II knockout (MT-null) and control mice were given acetaminophen (150-500 mg/kg i.p.), and liver injury was assessed 24 h later. MT-null mice were more susceptible than controls to acetaminophen-induced lethality and hepatotoxicity, as evidenced by elevated serum enzyme activities and histopathology. Zinc pretreatment, a method of MT induction, protected against acetaminophen hepatotoxicity in control mice, but not in MT-null mice. The susceptibility of MT-null mice to acetaminophen hepatotoxicity was not due to the increased acetaminophen bioactivation, as cytochrome P-450 enzymes, and acetaminophen-reactive metabolites in bile and urine were not increased in MT-null mice. Western blots of liver cytosol indicated that acetaminophen covalent binding at 4 h increased with acetaminophen dose, but there was no consistent difference between control and MT-null mice. Acetaminophen injection depleted cellular glutathione similarly in both control and MT-null mice, but produced more lipid peroxidation in MT-null mice, as evidenced by the abundance of thiobarbiturate-reactive substances, and by immunohistochemical localization of 4-hydroxynonenal and malondialdehyde protein adducts. MT-null hepatocytes were more susceptible than control cells to oxidative stress and cytotoxicity produced by N-acetylbenzoquinoneimine, a reactive metabolite of acetaminophen, as determined by oxidation of 2', 7'-dichlorofluorescin diacetate and lactate dehydrogenase leakage. In summary, this study demonstrated that MT deficiency renders animals more vulnerable to acetaminophen-induced hepatotoxicity. The increased sensitivity does not appear to be due to increased acetaminophen activation, glutathione depletion, or covalent binding, but appears to be associated with the antioxidant role of MT. JF - The Journal of pharmacology and experimental therapeutics AU - Liu, J AU - Liu, Y AU - Hartley, D AU - Klaassen, C D AU - Shehin-Johnson, S E AU - Lucas, A AU - Cohen, S D AD - University of Kansas Medical Center, Kansas City, USA. liu6@niehs.nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 580 EP - 586 VL - 289 IS - 1 SN - 0022-3565, 0022-3565 KW - Analgesics, Non-Narcotic KW - 0 KW - Acetaminophen KW - 362O9ITL9D KW - Metallothionein KW - 9038-94-2 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Liver -- pathology KW - Biotransformation KW - Glutathione -- metabolism KW - Oxidative Stress -- drug effects KW - Lipid Peroxidation -- drug effects KW - Mice KW - Mice, Knockout KW - Metallothionein -- deficiency KW - Chemical and Drug Induced Liver Injury -- pathology KW - Chemical and Drug Induced Liver Injury -- genetics KW - Analgesics, Non-Narcotic -- toxicity KW - Metallothionein -- genetics KW - Acetaminophen -- metabolism KW - Acetaminophen -- toxicity KW - Analgesics, Non-Narcotic -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69638786?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Metallothionein-I%2FII+knockout+mice+are+sensitive+to+acetaminophen-induced+hepatotoxicity.&rft.au=Liu%2C+J%3BLiu%2C+Y%3BHartley%2C+D%3BKlaassen%2C+C+D%3BShehin-Johnson%2C+S+E%3BLucas%2C+A%3BCohen%2C+S+D&rft.aulast=Liu&rft.aufirst=J&rft.date=1999-04-01&rft.volume=289&rft.issue=1&rft.spage=580&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-21 N1 - Date created - 1999-04-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of a receptor-binding region within domain 4 of the protective antigen component of anthrax toxin. AN - 69633967; 10085028 AB - Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin, whereas PA is the receptor-binding component. To identify residues of PA that are involved in interaction with the cellular receptor, two solvent-exposed loops of domain 4 of PA (amino acids [aa] 679 to 693 and 704 to 723) were mutagenized, and the altered proteins purified and tested for toxicity in the presence of LF. In addition to the intended substitutions, novel mutations were introduced by errors that occurred during PCR. Substitutions within the large loop (aa 704 to 723) had no effect on PA activity. A mutated protein, LST-35, with three substitutions in the small loop (aa 679 to 693), bound weakly to the receptor and was nontoxic. A mutated protein, LST-8, with changes in three separate regions did not bind to receptor and was nontoxic. Toxicity was greatly decreased by truncation of the C-terminal 3 to 5 aa, but not by their substitution with nonnative residues or the extension of the terminus with nonnative sequences. Comparison of the 28 mutant proteins described here showed that the large loop (aa 704 to 722) is not involved in receptor binding, whereas residues in and near the small loop (aa 679 to 693) play an important role in receptor interaction. Other regions of domain 4, in particular residues at the extreme C terminus, appear to play a role in stabilizing a conformation needed for receptor-binding activity. JF - Infection and immunity AU - Varughese, M AU - Teixeira, A V AU - Liu, S AU - Leppla, S H AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1860 EP - 1865 VL - 67 IS - 4 SN - 0019-9567, 0019-9567 KW - Antigens, Bacterial KW - 0 KW - Bacterial Toxins KW - Receptors, Peptide KW - anthrax toxin KW - anthrax toxin receptors KW - Index Medicus KW - Cytotoxicity, Immunologic KW - Animals KW - Base Sequence KW - Cells, Cultured KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Structure-Activity Relationship KW - Mutagenesis KW - Binding Sites KW - Bacterial Toxins -- genetics KW - Bacillus anthracis -- chemistry KW - Receptors, Peptide -- metabolism KW - Bacterial Toxins -- metabolism KW - Antigens, Bacterial -- metabolism KW - Bacillus anthracis -- genetics KW - Bacillus anthracis -- metabolism KW - Bacterial Toxins -- chemistry KW - Antigens, Bacterial -- genetics KW - Antigens, Bacterial -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69633967?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=Identification+of+a+receptor-binding+region+within+domain+4+of+the+protective+antigen+component+of+anthrax+toxin.&rft.au=Varughese%2C+M%3BTeixeira%2C+A+V%3BLiu%2C+S%3BLeppla%2C+S+H&rft.aulast=Varughese&rft.aufirst=M&rft.date=1999-04-01&rft.volume=67&rft.issue=4&rft.spage=1860&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-26 N1 - Date created - 1999-04-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunochemistry. 1965 Sep;2(3):235-54 [4956917] Mol Microbiol. 1994 Sep;13(6):1093-100 [7854123] J Biol Chem. 1986 Jun 5;261(16):7123-6 [3711080] Infect Immun. 1988 May;56(5):1066-9 [2895741] Infect Immun. 1991 Oct;59(10):3381-6 [1909998] J Biol Chem. 1991 Sep 15;266(26):17446-53 [1894632] J Biol Chem. 1991 Oct 25;266(30):20124-30 [1939073] EMBO J. 1992 Feb;11(2):575-83 [1537336] J Biol Chem. 1992 Aug 25;267(24):16872-7 [1512230] Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277-81 [1438214] Mol Biol Cell. 1992 Nov;3(11):1269-77 [1457831] PCR Methods Appl. 1991 Aug;1(1):17-24 [1842916] Science. 1993 Oct 8;262(5131):244-8 [8211143] Microbiology. 1996 Jul;142 ( Pt 7):1617-24 [8757726] Microbiology. 1996 Mar;142 ( Pt 3):707-15 [8868446] Mol Gen Mikrobiol Virusol. 1996 Jul-Sep;(3):16-20 [8999312] Nature. 1997 Feb 27;385(6619):833-8 [9039918] Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12059-64 [9342362] Mol Med. 1998 Feb;4(2):87-95 [9508786] Science. 1998 May 1;280(5364):734-7 [9563949] Biochem Biophys Res Commun. 1998 Jul 30;248(3):706-11 [9703991] J Gen Microbiol. 1961 Sep;26:49-63 [13916257] Infect Immun. 1988 Jul;56(7):1807-13 [3384478] Gene. 1988 Sep 30;69(2):287-300 [3148491] J Biol Chem. 1989 Nov 15;264(32):19103-7 [2509473] J Gen Microbiol. 1990 Jul;136(7):1211-5 [2121896] Mol Cell Biol. 1991 Apr;11(4):2200-5 [2005905] Science. 1991 Jun 21;252(5013):1703-5 [1904628] J Biol Chem. 1991 Aug 15;266(23):15493-7 [1651334] Infect Immun. 1993 Dec;61(12):5147-56 [8225592] J Biol Chem. 1994 Aug 12;269(32):20607-12 [8051159] J Biol Chem. 1994 Nov 18;269(46):29039-46 [7961869] Nature. 1973 Mar 30;242(5396):330-2 [4633459] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The rgg gene of Streptococcus pyogenes NZ131 positively influences extracellular SPE B production. AN - 69633867; 10085009 AB - Streptococcus pyogenes produces several extracellular proteins, including streptococcal erythrogenic toxin B (SPE B), also known as streptococcal pyrogenic exotoxin B and streptococcal proteinase. Several reports suggest that SPE B contributes to the virulence associated with S. pyogenes; however, little is known about its regulation. Nucleotide sequence data revealed the presence, upstream of the speB gene, of a gene, designated rgg, that was predicted to encode a polypeptide similar to previously described positive regulatory factors. The putative Rgg polypeptide of S. pyogenes NZ131 consisted of 280 amino acids and had a predicted molecular weight of 33,246. To assess the potential role of Rgg in the production of SPE B, the rgg gene was insertionally inactivated in S. pyogenes NZ131, which resulted in markedly decreased SPE B production, as determined both by immunoblotting and caseinolytic activity on agar plates. However, the production of other extracellular products, including streptolysin O, streptokinase, and DNase, was not affected. Complementation of the rgg mutant with an intact rgg gene copy in S. pyogenes NZ131 could restore SPE B production and confirmed that the rgg gene product is involved in the production of SPE B. JF - Infection and immunity AU - Chaussee, M S AU - Ajdic, D AU - Ferretti, J J AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. mchaussee@nih.gov Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1715 EP - 1722 VL - 67 IS - 4 SN - 0019-9567, 0019-9567 KW - Bacterial Proteins KW - 0 KW - DNA, Bacterial KW - DNA-Binding Proteins KW - Exotoxins KW - Membrane Proteins KW - SpeA protein, Streptococcus pyogenes KW - Trans-Activators KW - erythrogenic toxin KW - rgg protein, Streptococcus KW - 147415-86-9 KW - Deoxyribonucleases KW - EC 3.1.- KW - Streptokinase KW - EC 3.4.- KW - Index Medicus KW - Gene Expression Regulation, Bacterial KW - Amino Acid Sequence KW - Deoxyribonucleases -- metabolism KW - Sequence Analysis, DNA KW - Mutagenesis KW - Streptokinase -- metabolism KW - Base Sequence KW - Polymerase Chain Reaction -- methods KW - Genetic Complementation Test KW - Hemolysis KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- biosynthesis KW - Exotoxins -- biosynthesis KW - Streptococcus pyogenes -- genetics KW - Streptococcus pyogenes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69633867?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+immunity&rft.atitle=The+rgg+gene+of+Streptococcus+pyogenes+NZ131+positively+influences+extracellular+SPE+B+production.&rft.au=Chaussee%2C+M+S%3BAjdic%2C+D%3BFerretti%2C+J+J&rft.aulast=Chaussee&rft.aufirst=M&rft.date=1999-04-01&rft.volume=67&rft.issue=4&rft.spage=1715&rft.isbn=&rft.btitle=&rft.title=Infection+and+immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-26 N1 - Date created - 1999-04-26 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF091252; GENBANK N1 - SuppNotes - Cited By: J Mol Biol. 1975 Nov 5;98(3):503-17 [1195397] Can J Microbiol. 1994 Nov;40(11):930-6 [7804905] Mol Gen Genet. 1981;184(1):115-20 [6278245] Zentralbl Bakteriol Mikrobiol Hyg A. 1983 Sep;255(2-3):221-33 [6359775] Anal Biochem. 1984 Jan;136(1):89-92 [6424504] J Bacteriol. 1986 Mar;165(3):831-6 [3005240] Proc Natl Acad Sci U S A. 1987 Dec;84(23):8677-81 [2446327] Biochimie. 1988 Apr;70(4):559-66 [2844302] Infect Immun. 1988 Nov;56(11):2851-5 [2459063] Am Rev Respir Dis. 1988 Dec;138(6 Pt 2):S45-8 [2904779] Infect Immun. 1989 Feb;57(2):502-6 [2643572] Proc Natl Acad Sci U S A. 1989 Apr;86(7):2172-5 [2648393] N Engl J Med. 1989 Jul 6;321(1):1-7 [2659990] J Bacteriol. 1990 Aug;172(8):4536-42 [2198264] Lancet. 1990 Nov 10;336(8724):1167-71 [1978035] Infect Immun. 1995 Jan;63(1):9-20 [7806389] J Biol Chem. 1995 Apr 28;270(17):9862-7 [7730368] J Infect Dis. 1996 Apr;173(4):901-8 [8603969] J Exp Med. 1996 Aug 1;184(2):665-73 [8760820] J Bacteriol. 1996 Oct;178(19):5826-30 [8824637] Mol Microbiol. 1996 Sep;21(5):1087-99 [8885277] Infect Immun. 1996 Nov;64(11):4744-50 [8890235] Nature. 1965 Apr 3;206:33-4 [14334353] J Bacteriol. 1963 Dec;86:1270-4 [14086100] J Bacteriol. 1969 Sep;99(3):737-44 [5370276] Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Gen Microbiol. 1974 Jul;83(0):191-6 [4606912] Med Microbiol Immunol. 1996 Nov;185(3):171-81 [9007823] DNA Seq. 1997;7(2):83-95 [9063645] Infect Immun. 1997 May;65(5):1956-9 [9125588] J Clin Invest. 1997 Jun 1;99(11):2574-80 [9169486] Clin Infect Dis. 1997 Aug;25(2):260-6 [9332521] Mol Microbiol. 1998 Jan;27(2):299-310 [9484886] J Clin Microbiol. 1998 May;36(5):1428-9 [9574721] Infect Immun. 1998 Aug;66(8):3931-5 [9673282] Mol Microbiol. 1998 Jun;28(6):1323-34 [9680220] J Clin Invest. 1998 Aug 1;102(3):550-60 [9691092] EMBO J. 1998 Nov 2;17(21):6263-75 [9799235] J Infect Dis. 1954 Jul-Aug;95(1):1-12 [13184164] Infect Immun. 1991 Jan;59(1):211-5 [1987034] FEMS Microbiol Lett. 1991 Aug 1;66(2):219-24 [1936949] J Bacteriol. 1992 Jun;174(11):3577-86 [1534326] FEMS Microbiol Lett. 1992 Dec 15;100(1-3):313-22 [1478466] Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7676-80 [7689226] Infect Immun. 1993 Sep;61(9):3719-23 [8359893] Mol Gen Genet. 1993 Dec;241(5-6):685-93 [7505389] FEMS Microbiol Lett. 1994 Feb 1;116(1):107-12 [8132150] Microb Pathog. 1993 Nov;15(5):327-46 [7516997] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations. AN - 69630438; 10082584 AB - Loss of DNA mismatch repair due to mutation or diminished expression of the MLH1 gene is associated with genome instability and cancer. In this study, we used a yeast model system to examine three circumstances relevant to modulation of MLH1 function. First, overexpression of wild-type MLH1 was found to cause a strong elevation of mutation rates at three different loci, similar to the mutator effect of MLH1 gene inactivation. Second, haploid yeast strains with any of six mlh1 missense mutations that mimic germ line mutations found in human cancer patients displayed a strong mutator phenotype consistent with loss of mismatch repair function. Five of these mutations affect amino acids that are homologous to residues suggested by recent crystal structure and biochemical analysis of Escherichia coli MutL to participate in ATP binding and hydrolysis. Finally, using a highly sensitive reporter gene, we detected a mutator phenotype of diploid yeast strains that are heterozygous for mlh1 mutations. Evidence suggesting that this mutator effect results not from reduced mismatch repair in the MLH1/mlh1 cells but rather from loss of the wild-type MLH1 allele in a fraction of cells is presented. Exposure to bleomycin or to UV irradiation strongly enhanced mutagenesis in the heterozygous strain but had little effect on the mutation rate in the wild-type strain. This damage-induced hypermutability may be relevant to cancer in humans with germ line mutations in only one MLH1 allele. JF - Molecular and cellular biology AU - Shcherbakova, P V AU - Kunkel, T A AD - Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 3177 EP - 3183 VL - 19 IS - 4 SN - 0270-7306, 0270-7306 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - Fungal Proteins KW - MLH1 protein, S cerevisiae KW - Mutagens KW - Saccharomyces cerevisiae Proteins KW - MutL Protein Homolog 1 KW - EC 3.6.1.3 KW - Index Medicus KW - Phenotype KW - Models, Molecular KW - DNA Damage KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagens -- pharmacology KW - Mutation, Missense KW - Diploidy KW - Saccharomyces cerevisiae -- genetics KW - Fungal Proteins -- chemistry KW - Loss of Heterozygosity KW - DNA Repair KW - Fungal Proteins -- biosynthesis KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69630438?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Mutator+phenotypes+conferred+by+MLH1+overexpression+and+by+heterozygosity+for+mlh1+mutations.&rft.au=Shcherbakova%2C+P+V%3BKunkel%2C+T+A&rft.aulast=Shcherbakova&rft.aufirst=P&rft.date=1999-04-01&rft.volume=19&rft.issue=4&rft.spage=3177&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-20 N1 - Date created - 1999-04-20 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nat Genet. 1998 Aug;19(4):384-9 [9697702] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8698-702 [9671741] Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13759-64 [9811874] Cell. 1998 Nov 13;95(4):541-52 [9827806] Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2970-5 [10077621] Mutat Res. 1978 Jun;53(3):309-16 [79138] Mutat Res. 1978 Sep;58(1):41-9 [82205] Gene. 1988 Dec 30;74(2):527-34 [3073106] Genetics. 1989 May;122(1):19-27 [2659436] Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160-4 [1831267] Proc Natl Acad Sci U S A. 1992 May 1;89(9):3785-9 [1315039] Mol Cell Biol. 1994 Jan;14(1):407-15 [8264608] Science. 1994 Mar 18;263(5153):1625-9 [8128251] Science. 1994 Aug 19;265(5175):1091-3 [8066446] Carcinogenesis. 1994 Dec;15(12):2695-9 [8001223] Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1950-4 [7892206] Carcinogenesis. 1995 Aug;16(8):1717-22 [7634395] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Cancer Res. 1995 Dec 15;55(24):6092-6 [8521398] Nat Med. 1996 Feb;2(2):169-74 [8574961] Genes Dev. 1996 Feb 15;10(4):407-20 [8600025] Genes Dev. 1996 Jun 15;10(12):1433-42 [8666228] Eur J Biochem. 1996 Jun 1;238(2):297-307 [8681938] J Natl Cancer Inst. 1996 Sep 18;88(18):1317-9 [8797773] Annu Rev Biochem. 1996;65:101-33 [8811176] Cell. 1996 Oct 4;87(1):65-73 [8858149] Cancer Res. 1996 Dec 15;56(24):5728-33 [8971183] Cell. 1997 Jan 24;88(2):253-63 [9008166] Carcinogenesis. 1997 Jan;18(1):1-8 [9054582] Nature. 1997 Mar 27;386(6623):414-7 [9121560] Mol Cell Biol. 1997 May;17(5):2859-65 [9111358] Proc Natl Acad Sci U S A. 1997 May 27;94(11):5831-6 [9159160] Nat Struct Biol. 1997 Jun;4(6):477-82 [9187656] Genes Chromosomes Cancer. 1997 Jul;19(3):135-42 [9218993] Cell. 1997 Jul 11;90(1):65-75 [9230303] Mol Cell Biol. 1997 Aug;17(8):4465-73 [9234704] Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10144-9 [9294177] Hum Mutat. 1997;10(3):241-4 [9298827] Gastroenterology. 1997 Oct;113(4):1146-58 [9322509] Curr Biol. 1997 Oct 1;7(10):790-3 [9368761] Mutat Res. 1997 Dec;385(3):173-93 [9506887] J Biol Chem. 1998 Apr 17;273(16):9837-41 [9545323] Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5 [9618505] Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8568-73 [9671718] Mol Cell. 1998 Jul;2(1):9-22 [9702187] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Antifolates: the next millennium. AN - 69354968; 10598548 JF - Seminars in oncology AU - Allegra, C J AD - National Institutes of Health, Bethesda MD 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 1 EP - 2 VL - 26 IS - 2 Suppl 6 SN - 0093-7754, 0093-7754 KW - Antimetabolites, Antineoplastic KW - 0 KW - Enzyme Inhibitors KW - Folic Acid Antagonists KW - Glutamates KW - Pemetrexed KW - 04Q9AIZ7NO KW - Guanine KW - 5Z93L87A1R KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - Index Medicus KW - Animals KW - Humans KW - Thymidylate Synthase -- antagonists & inhibitors KW - Folic Acid Antagonists -- therapeutic use KW - Folic Acid Antagonists -- pharmacology KW - Enzyme Inhibitors -- therapeutic use KW - Glutamates -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Guanine -- analogs & derivatives KW - Glutamates -- therapeutic use KW - Antimetabolites, Antineoplastic -- therapeutic use KW - Guanine -- pharmacology KW - Guanine -- therapeutic use KW - Antimetabolites, Antineoplastic -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69354968?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Seminars+in+oncology&rft.atitle=Antifolates%3A+the+next+millennium.&rft.au=Allegra%2C+C+J&rft.aulast=Allegra&rft.aufirst=C&rft.date=1999-04-01&rft.volume=26&rft.issue=2+Suppl+6&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Seminars+in+oncology&rft.issn=00937754&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-12-21 N1 - Date created - 1999-12-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cancer Immunotherapy: Is There Real Progress at Last? AN - 19889183; 7478553 AB - This review summarises the evolution of recent major advances in cancer immunotherapy, using metastatic melanoma as a model. The first true clinical progress with immunotherapy developed from the application of recombinant DNA technology for the large scale production of immunostimulant cytokines. Clinical trials demonstrated that the systemic administration of recombinant high-dose bolus intravenous interleukin-2 (IL-2; 720 000 IU/kg every 8 hours) mediated objective tumour progression in 20% of patients with metastatic renal cancer and in 17% of patients with metastatic melanoma, with complete responses of 9% and 7%, respectively. The use of adoptive immunotherapy (the transfer of immune cells with anti-tumour activity to the tumour- bearing host) focused interest on T lymphocyte-mediated tumour recognition. Clinical trials described the systemic administration of lymphokine activated killer (LAK) cells and subsequently tumour infiltrating lymphocytes (TIL) to patients with advanced cancer. Although able to kill tumour targets in vitro, LAK cells did not prove useful for the treatment of patients with metastatic melanoma and renal cancer. A randomised trial, in which IL-2 was administered alone or with LAK cells, failed to show a difference in response rate or survival. In contrast, the treatment of 86 patients with metastatic melanoma using TIL plus IL-2 resulted in a 34% objective response rate, which included patients who had previously failed treatment with high-dose IL-2 alone. The focus on cellular immune responses, combined with rapid biotechnological advances, resulted in the identification of tumour specific antigens, such as MART-1 and gp100, that could be recognised by autologous TIL. This provided fundamental evidence of the existence of melanoma-associated antigens that were recognised in vivo by effector cells of the immune system. In vitro studies demonstrated immunodominant epitopes from MART-1 and gp100 that could induce in vitro-specific cytotoxic T lymphocyte reactivity. To enhance in vitro immunogenicity, single amino acid substitutions were made to identify peptides with higher affinity for HLA- A*0201. Modified peptides from gp100 were compared with the parental peptide for increased immunogenicity based on their ability to induce anti-tumour lymphocytes in vitro. From these studies, a candidate peptide was identified (G9-209-2M) which had increased immunogenic reactivity in vitro. Clinical trials demonstrated that the modified G9-209-2M peptide was more effective. Unfortunately, objective tumour regression was still low. However, when high-dose IL-2 was combined with G9-209-2M objective clinical responses increased to 42%. Efforts to find better ways to immunise against self antigens are ongoing and involve further peptide immunisations, as well as recombinant viral vectors, adjuvant cytokine therapy and cellular adjuvants such as dendritic cells. JF - BioDrugs AU - Kammula, U S AU - Marincola, F M AD - Surgery Branch, Division of Clinical Sciences, National Institutes of Health, Bethesda, Maryland, USA Y1 - 1999/04/01/ PY - 1999 DA - 1999 Apr 01 SP - 249 EP - 260 PB - Adis International Ltd., 41 Centorian Drive Private Bay 65901, Mairangi Bay Auckland 10 New Zealand, [mailto:sportsmed@adis.co.nz], [URL:http://www.adis.com] VL - 11 IS - 4 SN - 1173-8804, 1173-8804 KW - Virology & AIDS Abstracts; Immunology Abstracts; Biotechnology and Bioengineering Abstracts KW - Reviews-on-treatment KW - Immunotherapies, therapeutic-use KW - Aldesleukin, therapeutic-use KW - Cancer, treatment KW - Malignant-melanoma, treatment KW - Melanoma-vaccine-Genzyme-Molecular-Oncology, thera KW - Tumour-infiltrating-lymphocytes, therapeutic-use KW - Research-and-development KW - Melanoma-vaccine, therapeutic-use KW - Antineoplastics, therapeutic-use KW - Biotechnology KW - Anticancer-vaccines, therapeutic-use KW - Histocompatibility antigen HLA KW - Cell survival KW - Lymphokine-activated killer cells KW - Amino acid substitution KW - Interleukin 2 KW - Immunotherapy KW - Immune system KW - Adjuvants KW - Clinical trials KW - Melanoma KW - Metastases KW - Dendritic cells KW - Melanoma-associated antigen KW - Glycoprotein gp100 KW - Lymphocytes T KW - Immunostimulants KW - Epitopes KW - Intravenous administration KW - Immunization KW - Autoantigens KW - Cancer KW - Effector cells KW - Cytotoxicity KW - MART-1 antigen KW - Immunogenicity KW - Adoptive immunotherapy KW - Kidney KW - DNA KW - Lymphokines KW - Evolution KW - V 22350:Immunology KW - F 06955:Immunomodulation & Immunopharmacology KW - W 30915:Pharmaceuticals & Vaccines UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19889183?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=BioDrugs&rft.atitle=Cancer+Immunotherapy%3A+Is+There+Real+Progress+at+Last%3F&rft.au=Kammula%2C+U+S%3BMarincola%2C+F+M&rft.aulast=Kammula&rft.aufirst=U&rft.date=1999-04-01&rft.volume=11&rft.issue=4&rft.spage=249&rft.isbn=&rft.btitle=&rft.title=BioDrugs&rft.issn=11738804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2007-07-01 N1 - Last updated - 2015-04-01 N1 - SubjectsTermNotLitGenreText - Lymphokine-activated killer cells; Cell survival; Histocompatibility antigen HLA; Amino acid substitution; Interleukin 2; Immune system; Immunotherapy; Adjuvants; Clinical trials; Melanoma; Metastases; Dendritic cells; Melanoma-associated antigen; Glycoprotein gp100; Lymphocytes T; Immunostimulants; Epitopes; Intravenous administration; Cancer; Autoantigens; Immunization; Effector cells; Cytotoxicity; MART-1 antigen; Immunogenicity; Adoptive immunotherapy; DNA; Kidney; Lymphokines; Evolution ER - TY - JOUR T1 - Tea drinking and cancer risk: epidemiologic evidence AN - 1859304340; 10202387 AB - Tea and tea compounds have been shown to inhibit carcinogenic processes in experimental animals, raising the possibility that tea drinking may lower cancer risk in humans. However, epidemiologic studies have produced inconsistent evidence on the relation between tea drinking and cancer risk. Ecological data show considerable international variation in tea consumption but relatively small differences in cancer rates. Results from case-control and cohort studies also are inconclusive. Nevertheless, high consumption of tea has been linked to a reduced risk of digestive tract cancers in a number of epidemiologic studies. A lack of detailed information on duration and amount of tea drinking, a narrow range of tea intake in some study populations, inadequate control for confounding, and potential biases in recall and reporting of tea drinking patterns in case-control studies may have contributed to the diverse findings. Further research is needed before definitive conclusions on tea's impact upon cancer risk in humans can be reached. JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) AU - Chow AU - Blot AU - McLaughlin AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/04// PY - 1999 DA - April 1999 SP - 197 VL - 220 IS - 4 SN - 0037-9727, 0037-9727 UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/1859304340?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.atitle=Tea+drinking+and+cancer+risk%3A+epidemiologic+evidence&rft.au=Chow%3BBlot%3BMcLaughlin&rft.aulast=Chow&rft.aufirst=&rft.date=1999-04-01&rft.volume=220&rft.issue=4&rft.spage=197&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Society+for+Experimental+Biology+and+Medicine.+Society+for+Experimental+Biology+and+Medicine+%28New+York%2C+N.Y.%29&rft.issn=00379727&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date created - 1999-04-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative stress AN - 17287069; 4525217 AB - Much has been learnt about oxidative stress from studies of Escherichia coli. Key regulators of the adaptive responses in this organism are the SoxRS and OxyR transcription factors, which induce the expression of antioxidant activities in response to O sub(2) times super(-) and H sub(2)O sub(2) stress, respectively. Recently, a variety of biochemical assays together with the characterization of strains carrying mutations affecting the antioxidant activities and the regulators have given general insights into the sources of oxidative stress, the damage caused by oxidative stress, defenses against the oxidative stress, and the mechanisms by which the stress is perceived. These studies have also shown that the oxidative stress responses are intimately coupled to other regulatory networks in the cell. JF - Current Opinion in Microbiology AU - Storz, G AU - Imlay, JA AD - Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA, storz@helix.nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 188 EP - 194 VL - 2 IS - 2 SN - 1369-5274, 1369-5274 KW - Microbiology Abstracts B: Bacteriology KW - Oxidative stress KW - Transcription factors KW - Regulators KW - Escherichia coli KW - Mutation KW - J 02812:Antibacterial Agents: Others UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17287069?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=Oxidative+stress&rft.au=Storz%2C+G%3BImlay%2C+JA&rft.aulast=Storz&rft.aufirst=G&rft.date=1999-04-01&rft.volume=2&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2FS1369-5274%2899%2980033-2 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Mutation; Regulators; Oxidative stress; Transcription factors DO - http://dx.doi.org/10.1016/S1369-5274(99)80033-2 ER - TY - JOUR T1 - Proteoglycan receptor binding by Neisseria gonorrhoeae MS11 is determined by the HV-1 region of OpaA AN - 17284094; 4514801 AB - The interaction of the OpaA protein of Neisseria gonorrhoeae MS11mk with heparan sulphate-containing proteoglycan receptors on Chang conjunctiva epithelial cells was examined using isolated receptor binding and cell adherence/internalization assays. OpaA deletion proteins, in which the four surface-exposed regions of the protein were deleted individually, and chimeric OpaA/B proteins, in which the surface-exposed regions of the OpaA and OpaB proteins were exchanged, were expressed in N. gonorrhoeae. The recombinant deletion proteins and the chimeric OpaA/B proteins were surface exposed in the outer membrane of N. gonorrhoeae. Isolated receptor-binding assays and Chang cell infection assays with OpaA deletion variants indicated that hypervariable region 1 was essential for the interaction of N. gonorrhoeae with the proteoglycan receptor. Expression of chimeric OpaA/B proteins confirmed the central role of hypervariable region 1 in receptor binding and demonstrated that this domain alone confers the invasive biological phenotype in a non-heparan sulphate proteoglycan-binding Opa protein. The other variable regions of OpaA enhanced receptor binding in the presence of region 1, but did not constitute binding domains on their own. The results indicate that proteoglycan receptor binding results from a hierarchical interaction between the variable domains of the OpaA protein of MS11mk. JF - Molecular Microbiology AU - Grant, CCR AU - Bos, M P AU - Belland, R J AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South 4th Street, Hamilton, MT 59840-2999, USA, rb11p@nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 233 EP - 242 VL - 32 IS - 2 SN - 0950-382X, 0950-382X KW - OpaA protein KW - Microbiology Abstracts B: Bacteriology KW - Proteoglycans KW - Conjunctiva KW - Epithelium KW - Heparin KW - Binding KW - Neisseria gonorrhoeae KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17284094?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Proteoglycan+receptor+binding+by+Neisseria+gonorrhoeae+MS11+is+determined+by+the+HV-1+region+of+OpaA&rft.au=Grant%2C+CCR%3BBos%2C+M+P%3BBelland%2C+R+J&rft.aulast=Grant&rft.aufirst=CCR&rft.date=1999-04-01&rft.volume=32&rft.issue=2&rft.spage=233&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae; Binding; Epithelium; Heparin; Proteoglycans; Conjunctiva ER - TY - JOUR T1 - Regulation by proteolysis: developmental switches AN - 17282702; 4525209 AB - The energy-dependent proteases originally defined in Escherichia coli have proven to have particularly important roles in bacterial developmental systems, including sporulation in Bacillus subtilis and cell cycle in Caulobacter. Degradation of key regulatory proteins participates, with regulation of synthesis and activity of the regulators, to ensure tight control and, where required, irreversible commitment of the cell to specific developmental pathways. JF - Current Opinion in Microbiology AU - Gottesman, S AD - Building 37, Room 2E18, Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA, susang@helix.nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 142 EP - 147 VL - 2 IS - 2 SN - 1369-5274, 1369-5274 KW - pathways KW - Microbiology Abstracts B: Bacteriology KW - Proteolysis KW - Caulobacter KW - Bacillus subtilis KW - Degradation KW - Cell cycle KW - Regulation KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17282702?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Current+Opinion+in+Microbiology&rft.atitle=Regulation+by+proteolysis%3A+developmental+switches&rft.au=Gottesman%2C+S&rft.aulast=Gottesman&rft.aufirst=S&rft.date=1999-04-01&rft.volume=2&rft.issue=2&rft.spage=142&rft.isbn=&rft.btitle=&rft.title=Current+Opinion+in+Microbiology&rft.issn=13695274&rft_id=info:doi/10.1016%2FS1369-5274%2899%2980025-3 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus subtilis; Caulobacter; Regulation; Proteolysis; Cell cycle; Degradation DO - http://dx.doi.org/10.1016/S1369-5274(99)80025-3 ER - TY - JOUR T1 - High frequency of codon 61 K-ras A[rarr]T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene AN - 17268172; 4542507 AB - Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras proto-oncogenes in chloroprene-induced lung and HG neoplasms. K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82). Both K- and H-ras codon 61 A[rarr]T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A[rarr]T transversion at K-ras codon 61. This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A[rarr]T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A[rarr]T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A[rarr]T transversion at K-ras codon 61. This differed from 1,3-butadiene, where K-ras codon 13 G[rarr]C transitions and H-ras codon 61 A[rarr]G transitions were the predominant mutations. The major finding of K-ras A[rarr]T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens. JF - Carcinogenesis AU - Sills, R S AU - Hong, H L AU - Melnick, R L AU - Boorman, G A AU - Devereux, T R AD - Environmental Toxicology Program, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA, sills@niehs.nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 657 EP - 662 VL - 20 IS - 4 SN - 0143-3334, 0143-3334 KW - chloroprene KW - chloroprene(-2chloro-1,3-butadiene) KW - isoprene KW - mice KW - Oncogenes & Growth Factors Abstracts; Toxicology Abstracts KW - Ras protein KW - 1,3-Butadiene KW - Lung KW - Harderian gland KW - X 24155:Biochemistry KW - B 26130:Ras and Ras related oncogenes (Rho/Rac/Ral) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17268172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Carcinogenesis&rft.atitle=High+frequency+of+codon+61+K-ras+A%5Brarr%5DT+transversions+in+lung+and+Harderian+gland+neoplasms+of+B6C3F1+mice+exposed+to+chloroprene+%282-chloro-1%2C3-butadiene%29+for+2+years%2C+and+comparisons+with+the+structurally+related+chemicals+isoprene+and+1%2C3-butadiene&rft.au=Sills%2C+R+S%3BHong%2C+H+L%3BMelnick%2C+R+L%3BBoorman%2C+G+A%3BDevereux%2C+T+R&rft.aulast=Sills&rft.aufirst=R&rft.date=1999-04-01&rft.volume=20&rft.issue=4&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Carcinogenesis&rft.issn=01433334&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Harderian gland; Ras protein; 1,3-Butadiene; Lung ER - TY - JOUR T1 - Serial levels of serum organochlorines during pregnancy and postpartum AN - 17257091; 4525415 AB - In utero exposure to dichlorodiphenyldichloroethene and polychlorinated biphenyls, within the range found in the general U.S. population, may produce detectable effects in offspring. To design studies of the effects of in utero organochlorine exposure, we obtained data on the relationship between gestational and perinatal maternal levels in females on several occasions. We studied 67 pregnant women in the United States who agreed to have their blood drawn once during each trimester and once postpartum. We examined the Pearson correlation coefficient between the natural logarithm of levels ( mu g/g serum lipid). The correlation, r, among levels in the first and third trimester was .86 and .77 for dichlorodiphenyldichloroethene and for polychlorinated biphenyls. Correlations among levels determined at other times (i.e., second trimester and postpartum) were similar. On the basis of these results, we suggest that in studies of the effects of in utero or perinatal exposure to the aforementioned compounds, the time when specimens are collected is not critical. JF - Archives of Environmental Health AU - Longnecker, M P AU - Klebanoff, MA AU - Gladen, B C AU - Berendes, H W AD - NIEHS Epidemiology Branch, P.O. Box 12233, MD A3-05, Research Triangle Park, NC 27709, USA Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 110 EP - 114 VL - 54 IS - 2 SN - 0003-9896, 0003-9896 KW - USA KW - dichlorodiphenyldichloroethene KW - man KW - Toxicology Abstracts KW - Organochlorine compounds KW - Intrauterine exposure KW - Neonates KW - PCB KW - Pregnancy KW - X 24153:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17257091?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+Environmental+Health&rft.atitle=Serial+levels+of+serum+organochlorines+during+pregnancy+and+postpartum&rft.au=Longnecker%2C+M+P%3BKlebanoff%2C+MA%3BGladen%2C+B+C%3BBerendes%2C+H+W&rft.aulast=Longnecker&rft.aufirst=M&rft.date=1999-04-01&rft.volume=54&rft.issue=2&rft.spage=110&rft.isbn=&rft.btitle=&rft.title=Archives+of+Environmental+Health&rft.issn=00039896&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Pregnancy; Neonates; Organochlorine compounds; Intrauterine exposure; PCB ER - TY - JOUR T1 - Calculation of population attributable risk for alcohol and breast cancer (United States) AN - 17254268; 4548124 AB - Objectives: Because of increasing evidence that alcohol may be causally associated with breast cancer, we reconsider the population attributable risk (PAR) for alcohol and breast cancer for the US adult female population using an effect estimate from a meta-analysis and incorporating a revised perspective on measurement error correction. Methods: To estimate PAR, we employed a formula appropriate to use with an adjusted effect estimate. To estimate intermediate quantities needed to apply that formula, we used adjusted relative risk estimates from a previously published meta-analysis, as well as SEER cancer statistics and general population data from the third National Health and Nutrition Examination Survey. We used relative risk estimates uncorrected for measurement error. Results: The estimated age-adjusted PAR for alcohol and breast cancer was 2.1%. Conclusions: Because of the modest association between alcohol and breast cancer and the generally moderate level of alcohol intake among US women, the proportion of breast cancer attributable to alcohol intake is small. Widespread efforts to reduce alcohol consumption would not have a substantial impact on breast cancer rates in this population. While selected subgroups of women might benefit from decreasing alcohol consumption, specific profiles for such women have yet to be defined and defended. JF - Cancer Causes & Control AU - Tseng, M AU - Weinberg, C R AU - Umbach, D M AU - Longnecker, M P AD - National Institute of Environmental Health Sciences Epidemiology Branch, Research Triangle Park, P.O. Box 12233 MD A3-05, Research Triangle Park, NC 27709, USA Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 119 EP - 123 VL - 10 IS - 2 SN - 0957-5243, 0957-5243 KW - USA KW - population studies KW - Risk Abstracts; Health & Safety Science Abstracts KW - Risk assessment KW - Alcohol KW - Breast cancer KW - Females KW - H 11000:Diseases/Injuries/Trauma KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17254268?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Causes+%26+Control&rft.atitle=Calculation+of+population+attributable+risk+for+alcohol+and+breast+cancer+%28United+States%29&rft.au=Tseng%2C+M%3BWeinberg%2C+C+R%3BUmbach%2C+D+M%3BLongnecker%2C+M+P&rft.aulast=Tseng&rft.aufirst=M&rft.date=1999-04-01&rft.volume=10&rft.issue=2&rft.spage=119&rft.isbn=&rft.btitle=&rft.title=Cancer+Causes+%26+Control&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Breast cancer; Alcohol; Risk assessment; Females ER - TY - JOUR T1 - Physical mapping of an origin of bidirectional replication at the centre of the Borrelia burgdorferi linear chromosome AN - 17238983; 4514818 AB - The Borrelia burgdorferi chromosome is linear, with telomeres characterized by terminal inverted repeats and covalently closed single-stranded hairpin loops. The replication mechanism of these unusual molecules is unknown. Previous analyses of bacterial chromosomes for which the complete sequence has been determined, including that of B. burgdorferi, revealed an abrupt switch in polarity of CG skew at known or putative origins of replication. We used nascent DNA strand analysis to physically map the B. burgdorferi origin to within a 2 kb region at the centre of the linear chromosome, and to show that replication proceeds bidirectionally from this origin. The results are consistent with replication models in which termination occurs at the telomeres after bidirectional, symmetrical elongation from the central origin. Sequences typical of origins of other bacterial chromosomes were not found at the origin of this spirochete. The most likely location of the replication origin of the linear chromosome is the 240 bp sequence between dnaA and dnaN where the switch in CG skew occurs. JF - Molecular Microbiology AU - Picardeau, M AU - Lobry, J R AU - Hinnebusch, B J AD - NIH, NIAID, Rocky Mountain Laboratories, Laboratory of Microbial Structure and Function, 903 S. 4th St., Hamilton, MT 59840, USA, joe_hinnebusch@nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 437 EP - 445 VL - 32 IS - 2 SN - 0950-382X, 0950-382X KW - dnaA gene KW - dnaN gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Telomeres KW - Chromosomes KW - Borrelia burgdorferi KW - Physical mapping KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17238983?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Microbiology&rft.atitle=Physical+mapping+of+an+origin+of+bidirectional+replication+at+the+centre+of+the+Borrelia+burgdorferi+linear+chromosome&rft.au=Picardeau%2C+M%3BLobry%2C+J+R%3BHinnebusch%2C+B+J&rft.aulast=Picardeau&rft.aufirst=M&rft.date=1999-04-01&rft.volume=32&rft.issue=2&rft.spage=437&rft.isbn=&rft.btitle=&rft.title=Molecular+Microbiology&rft.issn=0950382X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Borrelia burgdorferi; Physical mapping; Telomeres; Chromosomes ER - TY - JOUR T1 - Mapping of staphylococcal enterotoxin A functional binding sites and presentation by monoclonal antibodies and fusion proteins AN - 17229113; 4503730 AB - Staphylococal enterotoxins (SE) bind with high affinity to major histocompatibility complex (MHC) class II proteins and stimulate large number of T cells via the V beta region of the T-cell receptor (TCR). To map the epitopes of SE type A (SEA) involved in MHC binding and cell proliferation, 20 specific anti-SEA monoclonal antibodies (MAbs) and two large glutathione S-transferase fusion proteins corresponding to the amino and carboxy termini, respectively, of SEA were used. The functionality of these antibodies was tested, by MHC binding inhibition, interleukin-2 production, and T-cell proliferation assays. Moreover, I studied the ability of the MAbs to present SEA in vitro to human and murine cells and their reactivity with the two fusion proteins. This study showed that all of the MAbs have a defined effect on one or both immunological properties of SEA and were able to present SEA to human and murine cells. However, one MAb (4H8) recognized SEA but without any interference with its biological activities. When the MAbs were tested to react with the two fusion proteins representing the SEA molecule, all of the MAbs were negative except for two. These results confirmed the presence of two functionally different binding sites of SEA with MHC class II molecules and the importance of the disulfide loop for the mitogenic activity of SEA. I further demonstrated that MAbs can present SEA to immune cells independent of the site recognized by the antibody and that the integrity of the SEA molecule is very important for its functions. JF - Infection and Immunity AU - Mahana, W AD - NIAID Twinbrook II Facility, 12441 Parklawn Dr., Rockville, MD 20852, USA, wmahana@atlas.niaid.nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 1894 EP - 1900 VL - 67 IS - 4 SN - 0019-9567, 0019-9567 KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Interleukin 2 KW - Major histocompatibility complex KW - Antigen presentation KW - Glutathione transferase KW - Monoclonal antibodies KW - Staphylococcus KW - Enterotoxins KW - Fusion protein KW - F 06776:Cell cooperation (antigen presentation) KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17229113?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Mapping+of+staphylococcal+enterotoxin+A+functional+binding+sites+and+presentation+by+monoclonal+antibodies+and+fusion+proteins&rft.au=Mahana%2C+W&rft.aulast=Mahana&rft.aufirst=W&rft.date=1999-04-01&rft.volume=67&rft.issue=4&rft.spage=1894&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Staphylococcus; Enterotoxins; Glutathione transferase; Antigen presentation; Major histocompatibility complex; Monoclonal antibodies; Fusion protein; Interleukin 2 ER - TY - JOUR T1 - Carcinogenicity of dermally administered 1,2-dihydro-2,2,4-trimethylquinoline monomer in F344 rats and B6C3F sub(1) mice AN - 17228145; 4506523 AB - 1,2-Dihydro-2,2,4-trimethylquinoline (TMQ) was evaluated in a 2-year study in which groups of 60 male or female F344 rats received 0, 36 or 60 mg kg super(-1) (0, 0.022, or 0.037 mg cm super(-2)) and groups of 60 male or female B6C3F sub(1) mice received 0, 3.6 or 10 mg kg super(-1) (0, 0.00136, 0.00435 mg cm super(-2)) in acetone by topical administration. Survival of all treated groups was comparable to survival of controls. Mean body weights of female rats were lower than those of controls throughout the study but mean body weights of male rats and male and female mice were comparable to the mean body weights of controls. No neoplasms of the skin were observed in any group of rats or mice. Acanthosis at the site of application was increased in male and female rats that received 60 or 100 mg kg super(-1) and hyperkeratosis was increased in female rats that received 60 mg kg super(-1). The incidences of renal tubule adenoma and renal tubule adenoma or carcinoma were increased significantly in the 60 and 100 mg kg super(-1) groups of male rats. There were no neoplastic or non-neoplastic lesions in mice associated with exposure to 1,2-dihydro-2,2,4-trimethylquinoline. In a 1-year initiation-promotion study, groups of 30 female SENCAR mice received an initiating dose of 50 mg kg super(-1) 1,2-dihydro-2,2,4-trimethylquinoline followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), or an initiating dose of 7,12-dimethylbenzanthracene (DMBA) followed by promotion with 5, 10 or 25 mg kg super(-1) 1,2-dihydro-2,2,4-trimethylquinoline. Other groups served as initiator control, promoter control, vehicle control and positive control (DMBA initiation, TPA promotion). In this system, 1,2-dihydro-2,2,4-trimethylquinoline-initiated skin was not promoted by TPA, and DMBA-initiated skin was not promoted by 1,2-dihydro-2,2,4-trimethylquinoline. JF - Journal of Applied Toxicology AU - Irwin, R D AU - French, JE AU - Elwell, M AU - Haseman, J AU - Braun, A G AU - Voelker, F A AD - National Institute of Health, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709, USA Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 125 EP - 132 VL - 19 IS - 2 SN - 0260-437X, 0260-437X KW - 1,2-Dihydro-2,2,4-trimethylquinoline KW - mice KW - rats KW - Toxicology Abstracts KW - Carcinogenicity KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17228145?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Applied+Toxicology&rft.atitle=Carcinogenicity+of+dermally+administered+1%2C2-dihydro-2%2C2%2C4-trimethylquinoline+monomer+in+F344+rats+and+B6C3F+sub%281%29+mice&rft.au=Irwin%2C+R+D%3BFrench%2C+JE%3BElwell%2C+M%3BHaseman%2C+J%3BBraun%2C+A+G%3BVoelker%2C+F+A&rft.aulast=Irwin&rft.aufirst=R&rft.date=1999-04-01&rft.volume=19&rft.issue=2&rft.spage=125&rft.isbn=&rft.btitle=&rft.title=Journal+of+Applied+Toxicology&rft.issn=0260437X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Carcinogenicity ER - TY - JOUR T1 - The p47 super(phox-/-) mouse model of chronic granulomatous disease has normal granuloma formation and cytokine responses to Mycobacterium avium and Schistosoma mansoni eggs AN - 17225541; 4503699 AB - Chronic granulomatous disease (CGD) is a genetic disorder of NADPH oxidase in which phagocytes are defective in generating reactive oxidants. CGD patients suffer from recurrent infections and exuberant and persistent tissue granuloma formation. We hypothesized that abnormal granulomata in CGD may result from aberrant T-cell-mediated cytokine responses. To assess Th-1-type cytokine responses and granulomata, we challenged p47 super(phox-/-) and wild-type mice with avirulent (SmD) or virulent (SmT) variants of Mycobacterium avium 2-151. To assess Th-2-type cytokine responses and granulomata, we used Schistosoma mansoni eggs (SME). Mononuclear cells were harvested, and cytokine responses were determined by enzyme-linked immunosorbent assay or reverse transcriptase PCR. Following SmD or SmT challenge, splenocytes from p47 super(phox-/-) and wild-type mice generated similar polar Th-1 responses (increased levels of gamma interferon and basal levels of interleukin 4 [IL-4] and IL-5). By 8 weeks after SmT challenge, exuberant splenic granulomata developed in p47 super(phox-/-) and wild-type mice. After SME challenge, thoracic lymph node mononuclear cells from p47 super(phox-/-) and wild-type mice generated similar mixed Th-1 and Th-2 cytokine responses to SME antigen and concanavalin A. Peak lung granuloma sizes and rates of regression were similar in p47 super(phox-/-) and wild-type mice. These results suggest that exuberant granulomatous inflammation in CGD is probably not the result of skewing of T-cell responses toward the Th-1 or Th-2 pole. Appropriate regression of established tissue granulomata in p47 super(phox-/-) mice challenged with SME suggests that abnormal granuloma formation in CGD is stimulus dependent and is not an invariant feature of the disease. JF - Infection and Immunity AU - Segal, B H AU - Doherty, T M AU - Wynn, T A AU - Cheever, A W AU - Sher, A AU - Holland, S M AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Dr. MSc. 1886, Bethesda, MD 20892, USA, smh@nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 1659 EP - 1665 VL - 67 IS - 4 SN - 0019-9567, 0019-9567 KW - Concanavalin A KW - Mycobacterium avium KW - NADPH oxidase KW - SME antigen KW - Schistosoma mansoni KW - mice KW - p47phox protein KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Interleukin 4 KW - Interleukin 5 KW - Animal models KW - Granuloma KW - Phagocytes KW - Immune response KW - Chronic granulomatous disease KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17225541?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=The+p47+super%28phox-%2F-%29+mouse+model+of+chronic+granulomatous+disease+has+normal+granuloma+formation+and+cytokine+responses+to+Mycobacterium+avium+and+Schistosoma+mansoni+eggs&rft.au=Segal%2C+B+H%3BDoherty%2C+T+M%3BWynn%2C+T+A%3BCheever%2C+A+W%3BSher%2C+A%3BHolland%2C+S+M&rft.aulast=Segal&rft.aufirst=B&rft.date=1999-04-01&rft.volume=67&rft.issue=4&rft.spage=1659&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium avium; Immune response; Interleukin 4; Interleukin 5; Animal models; Chronic granulomatous disease; Phagocytes; Granuloma ER - TY - JOUR T1 - Oligomerization of anthrax toxin protective antigen and binding of lethal factor during endocytic uptake into mammalian cells AN - 17224317; 4503724 AB - The protective antigen (PA) protein of anthrax toxin binds to a cellular receptor and is cleaved by cell surface furin to produce a 63-kDa fragment (PA63). The receptor-bound PA63 oligomerizes to a heptamer and acts to translocate the catalytic moieties of the toxin, lethal factor (LF) and edema factor (EF), from endosomes to the cytosol. In this report, we used nondenaturing gel electrophoresis to show that each PA63 subunit in the heptamer can bind one LF molecule. Studies using PA immobilized on a plastic surface showed that monomeric PA63 is also able to bind LF. The internalization of PA and LF by cells was studied with radiolabeled and biotinylated proteins. Uptake was relatively slow, with a half-time of 30 min. The number of moles of LF internalized was nearly equal to the number of moles of PA subunit internalized. The essential role of PA oligomerization in LF translocation was shown with PA protein cleaved at residues 313-314. The oligomers formed by these proteins during uptake into cells were not as stable when subjected to heat and detergent as were those formed by native PA. The results show that the structure of the toxin proteins and the kinetics of proteolytic activation, LF binding, and internalization are balanced in a way that allows each PA63 subunit to internalize an LF molecule. This set of proteins has evolved to achieve highly efficient internalization and membrane translocation of the catalytic components, LF and EF. JF - Infection and Immunity AU - Singh, Y AU - Klimpel, K R AU - Goel, S AU - Swain, P K AU - Leppla, SH AD - Oral Infection and Immunity Branch, National Institute of Dental and Craniofactial Research, Bldg. 30, Rm. 309, NIH, Bethesda, MD 20892, USA, Leppla@nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 1853 EP - 1859 VL - 67 IS - 4 SN - 0019-9567, 0019-9567 KW - PA63 protein KW - double prime EF protein KW - double prime LF protein KW - double prime PA protein KW - lethal factor KW - protective antigen KW - Toxicology Abstracts; Microbiology Abstracts B: Bacteriology KW - Oligomerization KW - Anthrax KW - Bacillus anthracis KW - Gel electrophoresis KW - Toxins KW - J 02822:Biosynthesis and physicochemical properties KW - X 24171:Microbial UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17224317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Oligomerization+of+anthrax+toxin+protective+antigen+and+binding+of+lethal+factor+during+endocytic+uptake+into+mammalian+cells&rft.au=Singh%2C+Y%3BKlimpel%2C+K+R%3BGoel%2C+S%3BSwain%2C+P+K%3BLeppla%2C+SH&rft.aulast=Singh&rft.aufirst=Y&rft.date=1999-04-01&rft.volume=67&rft.issue=4&rft.spage=1853&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Bacillus anthracis; Oligomerization; Anthrax; Toxins; Gel electrophoresis ER - TY - JOUR T1 - The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1. A meta-analysis of 15 prospective cohort studies AN - 17221251; 4506186 AB - To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine. JF - New England Journal of Medicine AU - The International Perinatal HIV Group AD - The International Perinatal HIV Group; Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Executive Bldg., Rm. 4B11F, 6100 Executive Blvd. MSC 7510, Bethesda, MD 20892-7510, USA Y1 - 1999/04/01/ PY - 1999 DA - 1999 Apr 01 SP - 977 EP - 987 VL - 340 IS - 13 SN - 0028-4793, 0028-4793 KW - Cesarean section KW - HIV-1 KW - disease transmission KW - Risk Abstracts; Virology & AIDS Abstracts KW - Human immunodeficiency virus KW - Transmission (vertical) KW - Human immunodeficiency virus 1 KW - Disease transmission KW - V 22005:AIDS: Epidemiological aspects KW - R2 23060:Medical and environmental health UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17221251?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ariskabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=New+England+Journal+of+Medicine&rft.atitle=The+mode+of+delivery+and+the+risk+of+vertical+transmission+of+human+immunodeficiency+virus+type+1.+A+meta-analysis+of+15+prospective+cohort+studies&rft.au=The+International+Perinatal+HIV+Group&rft.aulast=The+International+Perinatal+HIV+Group&rft.aufirst=&rft.date=1999-04-01&rft.volume=340&rft.issue=13&rft.spage=977&rft.isbn=&rft.btitle=&rft.title=New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Disease transmission; Human immunodeficiency virus; Cesarean section; Transmission (vertical) ER - TY - JOUR T1 - Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons AN - 17175705; 4474397 AB - To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain. AmB was effective against both 263K and DY and prevented death in 18% of DY-infected animals. The AmB effect against strain 263K was more prominent in mice whose endogenous PrP gene had been inactivated by homologous recombination. It was unclear whether this difference was due to a change in the duration of the disease or to possible interactive effects between the mouse PrP gene and the drugs themselves. The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs. JF - Journal of Virology AU - Demaimay, R AU - Race, R AU - Chesebro, B AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840 USA, bchesebro@nih.gov Y1 - 1999/04// PY - 1999 DA - Apr 1999 SP - 3511 EP - 3513 VL - 73 IS - 4 SN - 0022-538X, 0022-538X KW - PrP protein KW - Syrian hamsters KW - amphotericin B KW - mice KW - polyene antibiotics KW - transmissible spongiform encephalopathy KW - treatment KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Animal models KW - Antibiotics KW - Scrapie KW - Transgenic mice KW - Neurons KW - Prion protein KW - W3 33056:Animal models of human disease KW - V 22130:Diseases associated with slow viruses KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17175705?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Virology&rft.atitle=Effectiveness+of+polyene+antibiotics+in+treatment+of+transmissible+spongiform+encephalopathy+in+transgenic+mice+expressing+Syrian+hamster+PrP+only+in+neurons&rft.au=Demaimay%2C+R%3BRace%2C+R%3BChesebro%2C+B&rft.aulast=Demaimay&rft.aufirst=R&rft.date=1999-04-01&rft.volume=73&rft.issue=4&rft.spage=3511&rft.isbn=&rft.btitle=&rft.title=Journal+of+Virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Scrapie; Antibiotics; Transgenic mice; Animal models; Prion protein; Neurons ER - TY - JOUR T1 - Complete regression of human B-cell lymphoma xenografts in mice treated with recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 at doses tolerated by cynomolgus monkeys. AN - 69619167; 10077166 AB - RFB4(dsFv)-PE38 is a recombinant immunotoxin in which the variable light domain (V(L)) is disulfide bonded via cysteine residues to the variable heavy domain (V(H)), which in turn is fused to PE38, a mutant form of Pseudomonas exotoxin A. RFB4 binds to CD22, which is a differentiation antigen expressed on the majority of B-cell leukemias and lymphomas. To examine the potential efficacy of RFB4(dsFv)-PE38 when administered at a dose schedule appropriate for phase I testing, mice bearing CA46 human CD22+ Burkitt's lymphoma xenografts were treated on alternate days i.v. for 3 doses (QOD x 3). Complete regressions were observed in 80% and 100% of mice treated with 200 and 275 microg/kg QOD x 3, respectively. The higher dose was 27% of the LD50 and 34% of the LD10 in mice. Because RFB4(dsFv)-PE38 is stable at 37 degrees C, it could also be given by continuous infusion using pumps placed in the peritoneal cavity; complete regressions also resulted from this mode of administration. To study toxicology, a pilot toxicology study of RFB4(dsFv)-PE38 was undertaken in cynomolgus monkeys, which like humans but unlike mice have CD22, which binds RFB4. Doses of 100 and 500 microg/kg i.v. QOD x 3 were well tolerated, indicating that a dose that cured tumors in mice was tolerated by primates. Based on these preclinical results, RFB4(dsFv)-PE38 is being developed for the treatment of patients with CD22-positive leukemias and lymphomas. JF - International journal of cancer AU - Kreitman, R J AU - Wang, Q C AU - FitzGerald, D J AU - Pastan, I AD - Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03/31/ PY - 1999 DA - 1999 Mar 31 SP - 148 EP - 155 VL - 81 IS - 1 SN - 0020-7136, 0020-7136 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Antigens, Differentiation, B-Lymphocyte KW - Bacterial Toxins KW - CD22 protein, human KW - Cd22 protein, mouse KW - Cell Adhesion Molecules KW - Exotoxins KW - Immunoglobulin Heavy Chains KW - Immunoglobulin Light Chains KW - Immunoglobulin Variable Region KW - Immunotoxins KW - Lectins KW - Recombinant Proteins KW - Sialic Acid Binding Ig-like Lectin 2 KW - Virulence Factors KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - toxA protein, Pseudomonas aeruginosa KW - EC 2.4.2.31 KW - Index Medicus KW - Immunoglobulin Light Chains -- metabolism KW - Animals KW - Immunoglobulin Heavy Chains -- immunology KW - Immunoglobulin Light Chains -- immunology KW - Recombinant Proteins -- pharmacology KW - Macaca fascicularis KW - Antibodies, Monoclonal -- metabolism KW - Humans KW - Immunoglobulin Variable Region -- immunology KW - Mice, Nude KW - Mice KW - Antibodies, Monoclonal -- pharmacology KW - Immunoglobulin Heavy Chains -- metabolism KW - Antibodies, Monoclonal -- immunology KW - Burkitt Lymphoma -- therapy KW - Neoplasm Transplantation KW - Immunoglobulin Variable Region -- metabolism KW - Transplantation, Heterologous KW - Immunotoxins -- pharmacokinetics KW - Exotoxins -- pharmacology KW - Lymphoma, B-Cell -- therapy KW - Immunotoxins -- toxicity KW - Antigens, Differentiation, B-Lymphocyte -- metabolism KW - Lymphoma, B-Cell -- immunology KW - Antigens, Differentiation, B-Lymphocyte -- immunology KW - Graft Survival -- immunology KW - Lymphoma, B-Cell -- pathology KW - Antigens, CD -- metabolism KW - Immunotoxins -- pharmacology KW - Antigens, CD -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69619167?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Complete+regression+of+human+B-cell+lymphoma+xenografts+in+mice+treated+with+recombinant+anti-CD22+immunotoxin+RFB4%28dsFv%29-PE38+at+doses+tolerated+by+cynomolgus+monkeys.&rft.au=Kreitman%2C+R+J%3BWang%2C+Q+C%3BFitzGerald%2C+D+J%3BPastan%2C+I&rft.aulast=Kreitman&rft.aufirst=R&rft.date=1999-03-31&rft.volume=81&rft.issue=1&rft.spage=148&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-31 N1 - Date created - 1999-03-31 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits. AN - 69663039; 10097188 AB - Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism-antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Kittles, R A AU - Long, J C AU - Bergen, A W AU - Eggert, M AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - Section on Population Genetics and Linkage, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD. 20852, USA. Y1 - 1999/03/30/ PY - 1999 DA - 1999 Mar 30 SP - 4204 EP - 4209 VL - 96 IS - 7 SN - 0027-8424, 0027-8424 KW - Genetic Markers KW - 0 KW - Index Medicus KW - Microsatellite Repeats KW - Genetic Variation KW - Reward KW - Haplotypes KW - Sex Characteristics KW - Finland KW - Humans KW - Exploratory Behavior KW - Dependency (Psychology) KW - Avoidance Learning KW - Male KW - Models, Genetic KW - Y Chromosome KW - Point Mutation KW - Personality -- genetics KW - Genetic Predisposition to Disease KW - Alcoholism -- genetics KW - Alcoholism -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69663039?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Cladistic+association+analysis+of+Y+chromosome+effects+on+alcohol+dependence+and+related+personality+traits.&rft.au=Kittles%2C+R+A%3BLong%2C+J+C%3BBergen%2C+A+W%3BEggert%2C+M%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Kittles&rft.aufirst=R&rft.date=1999-03-30&rft.volume=96&rft.issue=7&rft.spage=4204&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-12 N1 - Date created - 1999-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Science. 1973 Jan 12;179(4069):139-50 [4264585] Lancet. 1974 Apr 6;1(7858):626-7 [4132289] Science. 1976 Aug 13;193(4253):547-55 [959813] Proc Natl Acad Sci U S A. 1978 Jun;75(6):2868-72 [275857] Arch Gen Psychiatry. 1978 Aug;35(8):941-51 [354554] Behav Genet. 1979 May;9(3):219-26 [574005] Arch Gen Psychiatry. 1981 Aug;38(8):861-8 [7259422] Arch Gen Psychiatry. 1981 Sep;38(9):965-9 [7283667] J Clin Psychiatry. 1982 Oct;43(10):400-3 [7118833] Arch Gen Psychiatry. 1985 Feb;42(2):161-7 [3977542] Arch Gen Psychiatry. 1986 Dec;43(12):1131-6 [3778110] Psychiatr Dev. 1986 Autumn;4(3):167-226 [3809156] Science. 1987 Apr 24;236(4800):410-6 [2882604] J Mol Biol. 1987 Jun 5;195(3):457-70 [2821279] Genetics. 1987 Oct;117(2):343-51 [2822535] Arch Gen Psychiatry. 1989 Jul;46(7):613-6 [2472125] Behav Genet. 1990 Jan;20(1):137-56 [2189399] Genomics. 1990 Jul;7(3):325-30 [1973137] Arch Gen Psychiatry. 1991 Jan;48(1):19-28 [1984758] Ann Hum Genet. 1990 Oct;54(Pt 4):315-20 [2285219] J Abnorm Psychol. 1992 Feb;101(1):18-25 [1537964] J Subst Abuse. 1991;3(2):205-19 [1668227] JAMA. 1992 Oct 14;268(14):1877-82 [1404711] Genetics. 1993 Mar;133(3):737-49 [8454213] Genetics. 1993 Jul;134(3):959-69 [8349118] J Med Genet. 1993 Oct;30(10):857-65 [8230163] Arch Gen Psychiatry. 1994 Jan;51(1):20-7 [7506515] Arch Gen Psychiatry. 1994 Jan;51(1):28-33 [7506516] Nat Genet. 1993 Dec;5(4):368-75 [8298645] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3166-70 [8159720] Hum Mol Genet. 1994 Jan;3(1):115-23 [7909247] Nat Genet. 1992 Nov;2(3):204-11 [1345170] Mol Phylogenet Evol. 1994 Jun;3(2):102-13 [8075830] Science. 1994 Sep 30;265(5181):2037-48 [8091226] Genetics. 1995 May;140(1):403-9 [7635303] Behav Genet. 1995 Jul;25(4):357-60 [7575365] Nat Med. 1995 Jul;1(7):623-5 [7585135] Trends Genet. 1995 Nov;11(11):449-56 [8578602] Mol Biol Evol. 1995 Sep;12(5):914-20 [7476137] Gene. 1995 Nov 20;165(2):191-8 [8522174] Mol Biol Evol. 1996 Sep;13(7):943-53 [8752003] Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):12035-9 [8876258] Am J Hum Genet. 1996 Nov;59(5):983-9 [8900224] Am J Hum Genet. 1998 May;62(5):1171-9 [9545401] Am J Phys Anthropol. 1999 Apr;108(4):381-99 [10229384] Hereditas. 1972;71(2):195-236 [4680662] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis. AN - 69662646; 10097113 AB - At high concentrations, the tubule poison paclitaxel is able to kill cancer cells that express Bcl-2; it inhibits the antiapoptotic activity of Bcl-2 by inducing its phosphorylation. To localize the site on Bcl-2 regulated by phosphorylation, mutant forms of Bcl-2 were constructed. Mutant forms of Bcl-2 with an alteration in serine at amino acid 70 (S70A) or with deletion of a 60-aa loop region between the alpha1 and alpha2 helices (Deltaloop Bcl-2, which also deletes amino acid 70) were unable to be phosphorylated by paclitaxel treatment of MDA-MB-231 cells into which the genes for the mutant proteins were transfected. The Deltaloop mutant completely inhibited paclitaxel-induced apoptosis. In cells expressing the S70A mutant, paclitaxel induced about one-third the level of apoptosis seen with wild-type Bcl-2. To evaluate the role of mitogen-activated protein kinases (MAPKs) in Bcl-2 phosphorylation, the activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 was examined. Paclitaxel-induced apoptosis was associated with phosphorylation of Bcl-2 and activation of ERK and JNK MAPKs. If JNK activation was blocked by transfections with either a stress-activated protein kinase kinase dominant-negative (K-->R) gene (which prevents the activation of a kinase upstream of JNK) or MAPK phosphatase-1 gene (which dephosphorylates and inactivates JNK), Bcl-2 phosphorylation did not occur, and the cells were not killed by paclitaxel. By contrast, neither an ERK inhibitor (PD098059) nor p38 inhibitors (SB203580 and SB202190) had an effect on Bcl-2 phosphorylation. Thus, our data show that the antiapoptotic effects of Bcl-2 can be overcome by phosphorylation of Ser-70; forms of Bcl-2 lacking the loop region are much more effective at preventing apoptosis than wild-type Bcl-2 because they cannot be phosphorylated. JNK, but not ERK or p38 MAPK, appear to be involved in the phosphorylation of Bcl-2 induced by paclitaxel. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Srivastava, R K AU - Mi, Q S AU - Hardwick, J M AU - Longo, D L AD - Laboratory of Immunology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224-6825, USA. Y1 - 1999/03/30/ PY - 1999 DA - 1999 Mar 30 SP - 3775 EP - 3780 VL - 96 IS - 7 SN - 0027-8424, 0027-8424 KW - Proto-Oncogene Proteins c-bcl-2 KW - 0 KW - Recombinant Proteins KW - Serine KW - 452VLY9402 KW - Vincristine KW - 5J49Q6B70F KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - JNK Mitogen-Activated Protein Kinases KW - EC 2.7.11.24 KW - Mitogen-Activated Protein Kinases KW - Alanine KW - OF5P57N2ZX KW - Paclitaxel KW - P88XT4IS4D KW - Index Medicus KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Cytosol -- metabolism KW - Humans KW - Breast Neoplasms KW - Vincristine -- toxicity KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Phosphorylation KW - Transfection KW - Recombinant Proteins -- metabolism KW - Point Mutation KW - Mitochondria -- metabolism KW - Recombinant Proteins -- chemistry KW - Signal Transduction KW - Amino Acid Substitution KW - Female KW - Sequence Deletion KW - Proto-Oncogene Proteins c-bcl-2 -- chemistry KW - Paclitaxel -- toxicity KW - Apoptosis -- physiology KW - Proto-Oncogene Proteins c-bcl-2 -- metabolism KW - Apoptosis -- drug effects KW - Proto-Oncogene Proteins c-bcl-2 -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69662646?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Deletion+of+the+loop+region+of+Bcl-2+completely+blocks+paclitaxel-induced+apoptosis.&rft.au=Srivastava%2C+R+K%3BMi%2C+Q+S%3BHardwick%2C+J+M%3BLongo%2C+D+L&rft.aulast=Srivastava&rft.aufirst=R&rft.date=1999-03-30&rft.volume=96&rft.issue=7&rft.spage=3775&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-12 N1 - Date created - 1999-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Neuron. 1995 May;14(5):927-39 [7748560] Mol Cell Biol. 1998 Jun;18(6):3509-17 [9584191] Science. 1995 Nov 24;270(5240):1326-31 [7481820] EMBO J. 1995 Dec 1;14(23):5957-64 [8846788] Genes Dev. 1996 Jan 1;10(1):1-15 [8557188] Nature. 1996 Mar 7;380(6569):75-9 [8598911] Cancer Res. 1996 Jun 1;56(11):2506-9 [8653686] Blood. 1996 Jul 15;88(2):386-401 [8695785] J Cell Biochem. 1996 Jan;60(1):12-7 [8825410] J Cell Biochem. 1996 Jan;60(1):23-32 [8825412] Science. 1996 Nov 15;274(5290):1194-7 [8895468] Cancer Res. 1997 Jan 15;57(2):229-33 [9000560] Br J Cancer. 1993 Feb;67(2):205-8 [8431353] Cell. 1993 Oct 22;75(2):241-51 [7503812] Science. 1993 Nov 19;262(5137):1274-7 [8235659] J Cell Biol. 1994 Jan;124(1-2):1-6 [8294493] Cell. 1994 Mar 25;76(6):1025-37 [8137421] Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3309-13 [8159744] Nature. 1994 May 12;369(6476):156-60 [8177321] Cell. 1994 Jun 17;77(6):841-52 [7911739] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6569-73 [8022822] Nature. 1994 Sep 22;371(6495):346-7 [8090205] J Biol Chem. 1998 Jul 24;273(30):18984-91 [9668078] Cancer Res. 1998 Aug 1;58(15):3202-8 [9699642] Blood. 1998 Sep 1;92(5):1768-75 [9716607] Int J Oncol. 1998 Oct;13(4):659-64 [9735392] J Biol Chem. 1998 Sep 25;273(39):25436-42 [9738012] Mol Cell Biol. 1994 Dec;14(12):8376-84 [7969172] Genes Dev. 1994 Dec 15;8(24):2996-3007 [8001819] Science. 1995 Jan 20;267(5196):389-93 [7824938] Trends Biochem Sci. 1994 Nov;19(11):470-3 [7855889] Science. 1995 Mar 10;267(5203):1456-62 [7878464] J Bioenerg Biomembr. 1994 Oct;26(5):509-17 [7896766] J Biol Chem. 1995 Mar 31;270(13):7420-6 [7535770] J Biol Chem. 1995 Apr 14;270(15):8377-80 [7721728] Science. 1997 Feb 21;275(5303):1132-6 [9027315] EMBO J. 1997 Mar 3;16(5):968-77 [9118958] J Biol Chem. 1997 May 2;272(18):11671-3 [9115213] Cell. 1997 Aug 8;90(3):405-13 [9267021] J Biol Chem. 1997 Oct 3;272(40):25238-42 [9312139] Cancer Res. 1998 Apr 15;58(8):1609-15 [9563469] DNA Cell Biol. 1994 Jul;13(7):679-92 [7772249] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - GADD45 induction of a G2/M cell cycle checkpoint. AN - 69661150; 10097101 AB - G1/S and G2/M cell cycle checkpoints maintain genomic stability in eukaryotes in response to genotoxic stress. We report here both genetic and functional evidence of a Gadd45-mediated G2/M checkpoint in human and murine cells. Increased expression of Gadd45 via microinjection of an expression vector into primary human fibroblasts arrests the cells at the G2/M boundary with a phenotype of MPM2 immunopositivity, 4n DNA content and, in 15% of the cells, centrosome separation. The Gadd45-mediated G2/M arrest depends on wild-type p53, because no arrest was observed either in p53-null Li-Fraumeni fibroblasts or in normal fibroblasts coexpressed with p53 mutants. Increased expression of cyclin B1 and Cdc25C inhibited the Gadd45-mediated G2/M arrest in human fibroblasts, indicating that the mechanism of Gadd45-mediated G2/M checkpoint is at least in part through modulation of the activity of the G2-specific kinase, cyclin B1/p34(cdc2). Genetic and physiological evidence of a Gadd45-mediated G2/M checkpoint was obtained by using GADD45-deficient human or murine cells. Human cells with endogenous Gadd45 expression reduced by antisense GADD45 expression have an impaired G2/M checkpoint after exposure to either ultraviolet radiation or methyl methanesulfonate but are still able to undergo G2 arrest after ionizing radiation. Lymphocytes from gadd45-knockout mice (gadd45 -/-) also retained a G2/M checkpoint initiated by ionizing radiation and failed to arrest at G2/M after exposure to ultraviolet radiation. Therefore, the mammalian genome is protected by a multiplicity of G2/M checkpoints in response to specific types of DNA damage. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Wang, X W AU - Zhan, Q AU - Coursen, J D AU - Khan, M A AU - Kontny, H U AU - Yu, L AU - Hollander, M C AU - O'Connor, P M AU - Fornace, A J AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03/30/ PY - 1999 DA - 1999 Mar 30 SP - 3706 EP - 3711 VL - 96 IS - 7 SN - 0027-8424, 0027-8424 KW - CDKN1A protein, human KW - 0 KW - Cdkn1a protein, mouse KW - Cell Cycle Proteins KW - Cyclin-Dependent Kinase Inhibitor p21 KW - Cyclins KW - DNA-Binding Proteins KW - GADD45 protein KW - Intracellular Signaling Peptides and Proteins KW - Proteins KW - Recombinant Proteins KW - Tumor Suppressor Proteins KW - ATM protein, human KW - EC 2.7.11.1 KW - Ataxia Telangiectasia Mutated Proteins KW - Atm protein, mouse KW - Protein-Serine-Threonine Kinases KW - Index Medicus KW - Animals KW - Spleen -- cytology KW - DNA Damage KW - Humans KW - Mice KW - Fibroblasts -- cytology KW - Fibroblasts -- physiology KW - Mice, Inbred Strains KW - Tumor Cells, Cultured KW - Genes, p53 KW - Transfection KW - Recombinant Proteins -- metabolism KW - Mitosis KW - G2 Phase KW - Colonic Neoplasms KW - Cell Line KW - Cyclins -- genetics KW - Cell Cycle -- physiology KW - Lymphocytes -- cytology KW - Lymphocytes -- physiology KW - Proteins -- genetics KW - Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69661150?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=GADD45+induction+of+a+G2%2FM+cell+cycle+checkpoint.&rft.au=Wang%2C+X+W%3BZhan%2C+Q%3BCoursen%2C+J+D%3BKhan%2C+M+A%3BKontny%2C+H+U%3BYu%2C+L%3BHollander%2C+M+C%3BO%27Connor%2C+P+M%3BFornace%2C+A+J%3BHarris%2C+C+C&rft.aulast=Wang&rft.aufirst=X&rft.date=1999-03-30&rft.volume=96&rft.issue=7&rft.spage=3706&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-12 N1 - Date created - 1999-05-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Bioessays. 1995 Jun;17(6):501-8 [7575491] Genes Dev. 1994 Oct 15;8(20):2401-15 [7958905] Oncogene. 1995 Nov 16;11(10):1931-7 [7478510] Science. 1996 Mar 22;271(5256):1744-7 [8596939] Genes Dev. 1996 May 1;10(9):1054-72 [8654922] Proc Natl Acad Sci U S A. 1996 May 14;93(10):4827-32 [8643488] Genes Dev. 1996 May 15;10(10):1219-32 [8675009] Nature. 1996 Jun 20;381(6584):713-6 [8649519] Biochim Biophys Acta. 1996 Jun 7;1287(2-3):77-102 [8672531] J Cell Sci. 1996 May;109 ( Pt 5):1105-12 [8743957] Genes Dev. 1996 Oct 1;10(19):2438-51 [8843196] Oncogene. 1996 Nov 21;13(10):2255-63 [8950993] Science. 1989 Nov 3;246(4930):629-34 [2683079] Mol Cell Biol. 1989 Oct;9(10):4196-203 [2573827] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766-70 [2141171] Oncogene. 1990 Jun;5(6):795-81 [2141683] Science. 1994 Nov 25;266(5189):1376-80 [7973727] Science. 1994 Dec 16;266(5192):1821-8 [7997877] Oncogene. 1995 Jan 5;10(1):109-15 [7529916] Science. 1995 Mar 3;267(5202):1353-6 [7871434] Oncogene. 1995 Mar 16;10(6):1053-9 [7700629] Cancer Res. 1995 Apr 15;55(8):1643-8 [7712468] Oncogene. 1995 Jun 1;10(11):2263-70 [7784074] Oncogene. 1995 Jun 15;10(12):2427-33 [7784094] Science. 1995 Jun 23;268(5218):1749-53 [7792600] Cell. 1995 Aug 25;82(4):675-84 [7664346] Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8493-7 [7667317] Cell. 1995 Sep 8;82(5):831-40 [7545545] Oncogene. 1995 Oct 19;11(8):1427-35 [7478567] Cell. 1997 Feb 7;88(3):315-21 [9039258] Cell. 1997 Feb 7;88(3):323-31 [9039259] Science. 1997 Sep 5;277(5331):1495-7 [9278510] Science. 1997 Sep 5;277(5331):1497-501 [9278511] Science. 1997 Sep 5;277(5331):1501-5 [9278512] Nature. 1998 Jan 15;391(6664):295-8 [9440695] Mol Cell. 1997 Dec;1(1):3-11 [9659898] Science. 1998 Nov 20;282(5393):1497-501 [9822382] EMBO J. 1990 Sep;9(9):2885-9 [2167834] Mol Cell Biol. 1991 Feb;11(2):1009-16 [1990262] Nature. 1991 Jun 6;351(6326):453-6 [2046748] Science. 1991 Jul 5;253(5015):49-53 [1905840] Nature. 1991 Jul 25;352(6333):345-7 [1852210] Cancer Res. 1991 Dec 1;51(23 Pt 1):6304-11 [1933891] Cell Motil Cytoskeleton. 1991;20(2):121-35 [1751966] Nature. 1992 Mar 19;356(6366):215-21 [1552940] EMBO J. 1992 Apr;11(4):1343-50 [1563350] Cell. 1992 Apr 17;69(2):367-74 [1348971] Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495-9 [1584781] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491-5 [1323840] Cell. 1992 Sep 18;70(6):937-48 [1525830] J Cell Biol. 1992 Nov;119(3):493-501 [1400587] Cell. 1992 Nov 13;71(4):587-97 [1423616] Cell. 1993 Nov 19;75(4):653-60 [8242741] Cell. 1993 Nov 19;75(4):765-78 [8242748] Cell. 1993 Nov 19;75(4):805-16 [8242751] Cell. 1993 Nov 19;75(4):817-25 [8242752] Nature. 1993 Dec 16;366(6456):701-4 [8259214] Int J Radiat Biol. 1994 Feb;65(2):175-84 [7907115] Exp Cell Res. 1994 Mar;211(1):90-8 [8125163] Mol Cell Biol. 1994 Apr;14(4):2361-71 [8139541] Genes Dev. 1994 Mar 15;8(6):652-65 [7926756] Blood. 1994 Dec 1;84(11):3781-4 [7949134] Cell. 1994 Nov 18;79(4):563-71 [7954823] Oncogene. 1995 Nov 2;11(9):1675-83 [7478594] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Strict conservation of the retroviral nucleocapsid protein zinc finger is strongly influenced by its role in viral infection processes: characterization of HIV-1 particles containing mutant nucleocapsid zinc-coordinating sequences. AN - 69640864; 10087230 AB - The retroviral nucleocapsid (NC) protein contains highly conserved amino acid sequences (-Cys-X2-Cys-X4-His-X4-Cys-) designated retroviral (CCHC) Zn2+ fingers. The NC protein of murine leukemia viruses contains one NC Zn2+ finger and mutants that were competent in metal binding (CCCC and CCHH) packaged wild-type levels of full-length viral RNA but were not infectious. These studies were extended to human immunodeficiency virus type 1 (HIV-1), a virus with two NC Zn2+ fingers. Viruses with combinations of CCHC, CCCC, and CCHH Zn2+ fingers in each position of HIV-1 NC were characterized. Mutant particles contained the normal complement of processed viral proteins. Four mutants packaged roughly wild-type levels of genomic RNA, whereas the remaining mutants packaged reduced levels. Virions with mutated C-terminal position NC fingers were replication competent. One interesting mutant, containing a CCCC Zn2+ finger in the N-terminal position of NC, packaged wild-type levels of viral RNA and showed approximately 5% wild-type levels of infectivity when examined in CD4-expressing HeLa cells containing an HIV-1 LTR/beta-galactosidase construct. However, this particular mutant was replication defective in H9 cells; all other mutants were replication defective over the 8-week course of the assay. Two long terminal repeat viral DNA species could be detected in the CCCC mutant but not in any of the other replication-defective mutants. These studies show that the N-terminal Zn2+ finger position is more sensitive to alterations than the C-terminal position with respect to replication. Additionally, the retroviral (CCHC) NC Zn2+ finger is required for early infection processes. The evolutionary pressure to maintain CCHC NC Zn2+ fingers depends mainly on its function in infection processes, in addition to its function in genome packaging. JF - Virology AU - Gorelick, R J AU - Gagliardi, T D AU - Bosche, W J AU - Wiltrout, T A AU - Coren, L V AU - Chabot, D J AU - Lifson, J D AU - Henderson, L E AU - Arthur, L O AD - SAIC Frederick, National Cancer Institute, Frederick, Maryland, 21702-1201, USA.gorelick@avpaxp1.ncifcrf.gov Y1 - 1999/03/30/ PY - 1999 DA - 1999 Mar 30 SP - 92 EP - 104 VL - 256 IS - 1 SN - 0042-6822, 0042-6822 KW - DNA Primers KW - 0 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - HeLa Cells KW - Humans KW - Amino Acid Sequence KW - Mutagenesis, Site-Directed KW - HIV Long Terminal Repeat KW - Polymerase Chain Reaction KW - Base Sequence KW - Conserved Sequence KW - Transfection KW - Molecular Sequence Data KW - Zinc Fingers KW - Amino Acid Substitution KW - Cell Line KW - HIV-1 -- genetics KW - Nucleocapsid -- metabolism KW - Nucleocapsid -- genetics KW - HIV-1 -- pathogenicity KW - Nucleocapsid -- chemistry KW - HIV-1 -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69640864?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Strict+conservation+of+the+retroviral+nucleocapsid+protein+zinc+finger+is+strongly+influenced+by+its+role+in+viral+infection+processes%3A+characterization+of+HIV-1+particles+containing+mutant+nucleocapsid+zinc-coordinating+sequences.&rft.au=Gorelick%2C+R+J%3BGagliardi%2C+T+D%3BBosche%2C+W+J%3BWiltrout%2C+T+A%3BCoren%2C+L+V%3BChabot%2C+D+J%3BLifson%2C+J+D%3BHenderson%2C+L+E%3BArthur%2C+L+O&rft.aulast=Gorelick&rft.aufirst=R&rft.date=1999-03-30&rft.volume=256&rft.issue=1&rft.spage=92&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-04 N1 - Date created - 1999-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Deduction of consensus binding sequences on proteins that bind IIA super(Glc) of the phosphoenolpyruvate:sugar phosphotransferase system by cysteine scanning mutagenesis of Escherichia coli lactose permease AN - 17209275; 4493017 AB - Mediated by the protein IIA super(Glc), the phosphoenolpyruvate:sugar phosphotransferase system plays a role in the regulation of activity of other sugar transport systems in Escherichia coli. By using a direct binding assay, a collection of single-Cys replacement mutants in cytoplasmic loops of lactose permease were evaluated for their capacity to bind IIA super(Glc). Selected Cys replacements in loops IV/V or VI/VII result in loss of binding activity. Analysis of the mutagenesis results together with multiple sequence alignments of a family of proteins that interacts with IIA super(Glc) provides the basis for developing two regions of consensus sequence in those partner proteins necessary for binding to IIA super(Glc). The requirement for two interaction regions is interpreted in the regulatory framework of a substrate-dependent conformational change that brings those two regions into an orientation optimal for binding IIA super(Glc). JF - Proceedings of the National Academy of Sciences, USA AU - Sondej, M AU - Sun, J AU - Seok, Y AU - Kaback, H R AU - Peterkofsky, A AD - Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, alan@codon.nih.gov Y1 - 1999/03/30/ PY - 1999 DA - 1999 Mar 30 SP - 3525 EP - 3530 VL - 96 IS - 07 SN - 0027-8424, 0027-8424 KW - IIA super(Glc) protein KW - cysteine scanning mutagenesis KW - lactose permease KW - nucleotide sequence KW - phospho-enol-pyruvate:sugar phosphotransferase KW - phosphoenolpyruvate-carbohydrate phosphotransferase KW - Biochemistry Abstracts 2: Nucleic Acids; Microbiology Abstracts B: Bacteriology KW - Escherichia coli KW - Substrate specificity KW - Conformation KW - Mutagenesis KW - J 02728:Enzymes KW - N 14681:Mutagenesis techniques UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17209275?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Deduction+of+consensus+binding+sequences+on+proteins+that+bind+IIA+super%28Glc%29+of+the+phosphoenolpyruvate%3Asugar+phosphotransferase+system+by+cysteine+scanning+mutagenesis+of+Escherichia+coli+lactose+permease&rft.au=Sondej%2C+M%3BSun%2C+J%3BSeok%2C+Y%3BKaback%2C+H+R%3BPeterkofsky%2C+A&rft.aulast=Sondej&rft.aufirst=M&rft.date=1999-03-30&rft.volume=96&rft.issue=07&rft.spage=3525&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Substrate specificity; Mutagenesis; Conformation ER - TY - JOUR T1 - Brain-derived and glial cell line-derived neurotrophic factors protect a catecholaminergic cell line from dopamine-induced cell death. AN - 69702032; 10213158 AB - Brain-derived neurotrophic factor (BDNF) promotes the survival of dopaminergic neurons in primary cultures and protects these neurons from the neurotoxic effects of 6-hydroxydopamine. The protective mechanism of BDNF on neurotoxicity was evaluated using CATH.a cells, a clonal catecholaminergic cell line derived from the central nervous system. Dopamine produced a dose-dependent cell death in CATH.a cells. Treatment of CATH.a cells with BDNF or glia cell line-derived neurotrophic factor (GDNF) reduced dopamine-induced cell death by approximately 60-70%. Nerve growth factor, basic fibroblast growth factor, neurotrophin-4/5 and insulin had no protective effect on dopamine-induced cell death. Dopamine decreased the activity of superoxide dismutase and the levels of glutathione in the CATH.a cells and these decreases were reversed by BDNF. In addition, BDNF treatment alone increased superoxide dismutase activity by 108%. These results suggest that BDNF may safeguard CATH.a cells from dopamine-induced cell death by maintaining or enhancing components of the cell, which protect from oxidative stress. JF - Neuroscience letters AU - Gong, L AU - Wyatt, R J AU - Baker, I AU - Masserano, J M AD - National Institute of Mental Health, Neuropsychiatry Branch, Bethesda, MD 20892-2668, USA. Y1 - 1999/03/26/ PY - 1999 DA - 1999 Mar 26 SP - 153 EP - 156 VL - 263 IS - 2-3 SN - 0304-3940, 0304-3940 KW - Brain-Derived Neurotrophic Factor KW - 0 KW - Glial Cell Line-Derived Neurotrophic Factor KW - Insulin KW - Nerve Growth Factors KW - Nerve Tissue Proteins KW - Neuroprotective Agents KW - Fibroblast Growth Factor 2 KW - 103107-01-3 KW - Superoxide Dismutase KW - EC 1.15.1.1 KW - Glutathione KW - GAN16C9B8O KW - neurotrophin 4 KW - P658DCA9XD KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Fibroblast Growth Factor 2 -- pharmacology KW - Animals KW - Nerve Growth Factors -- pharmacology KW - Kinetics KW - Glutathione -- metabolism KW - Superoxide Dismutase -- metabolism KW - Insulin -- pharmacology KW - Central Nervous System KW - Cell Line KW - Nerve Tissue Proteins -- physiology KW - Brain-Derived Neurotrophic Factor -- physiology KW - Brain-Derived Neurotrophic Factor -- pharmacology KW - Cell Death -- drug effects KW - Nerve Tissue Proteins -- pharmacology KW - Neuroprotective Agents -- pharmacology KW - Dopamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69702032?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+letters&rft.atitle=Brain-derived+and+glial+cell+line-derived+neurotrophic+factors+protect+a+catecholaminergic+cell+line+from+dopamine-induced+cell+death.&rft.au=Gong%2C+L%3BWyatt%2C+R+J%3BBaker%2C+I%3BMasserano%2C+J+M&rft.aulast=Gong&rft.aufirst=L&rft.date=1999-03-26&rft.volume=263&rft.issue=2-3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Neuroscience+letters&rft.issn=03043940&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-10 N1 - Date created - 1999-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - SecA Is Required for the Insertion of Inner Membrane Proteins Targeted by the Escherichia coli Signal Recognition Particle AN - 17197159; 4482216 AB - Recent work has demonstrated that the signal recognition particle (SRP) is required for the efficient insertion of many proteins into the Escherichia coli inner membrane (IM). Based on an analogy to eukaryotic SRP, it is likely that bacterial SRP binds to inner membrane proteins (IMPs) co-translationally and then targets them to protein transport channels ("translocons"). Here we present evidence that SecA, which has previously been shown to facilitate the export of proteins targeted in a post-translational fashion, is also required for the membrane insertion of proteins targeted by SRP. The introduction of SecA mutations into strains that have modest SRP deficiencies produced a synthetic lethal effect, suggesting that SecA and SRP might function in the same biochemical pathway. Consistent with this explanation depletion of SecA by inactivating a temperature- sensitive amber suppressor in a secAam strain completely blocked the membrane insertion of AcrB, a protein that is targeted by SRP. In the absence of substantial SecA, pulse-labeled AcrB was retained in the cytoplasm even after a prolonged chase period and was eventually degraded. Although protein export was also severely impaired by SecA depletion, the observation that more than 20% of the OmpA molecules were translocated properly showed that translocons were still active. Taken together, these results imply that SecA plays a much broader role in the transport of proteins across the E. coli IM than has been previously recognized. JF - Journal of Biological Chemistry AU - Qi, H AU - Bernstein, H D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892- 1810 Y1 - 1999/03/26/ PY - 1999 DA - 1999 Mar 26 SP - 8993 EP - 8997 VL - 274 IS - 13 SN - 0021-9258, 0021-9258 KW - SecA protein KW - signal recognition particle KW - translocons KW - Microbiology Abstracts B: Bacteriology KW - Inner membranes KW - Escherichia coli KW - Membrane proteins KW - J 02727:Amino acids, peptides and proteins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17197159?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=SecA+Is+Required+for+the+Insertion+of+Inner+Membrane+Proteins+Targeted+by+the+Escherichia+coli+Signal+Recognition+Particle&rft.au=Qi%2C+H%3BBernstein%2C+H+D&rft.aulast=Qi&rft.aufirst=H&rft.date=1999-03-26&rft.volume=274&rft.issue=13&rft.spage=8993&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Inner membranes; Membrane proteins ER - TY - JOUR T1 - Role of the extracellular loops of G protein-coupled receptors in ligand recognition: a molecular modeling study of the human P2Y1 receptor. AN - 69650733; 10090736 AB - The P2Y1 receptor is a G protein-coupled receptor (GPCR) and is stimulated by extracellular ADP and ATP. Site-directed mutagenesis of the three extracellular loops (ELs) of the human P2Y1 receptor indicates the existence of two essential disulfide bridges (Cys124 in EL1 and Cys202 in EL2; Cys42 in the N-terminal segment and Cys296 in EL3) and several specific ionic and H-bonding interactions (involving Glu209 and Arg287). Through molecular modeling and molecular dynamics simulations, an energetically sound conformational hypothesis for the receptor has been calculated that includes transmembrane (TM) domains (using the electron density map of rhodopsin as a template), extracellular loops, and a truncated N-terminal region. ATP may be docked in the receptor, both within the previously defined TM cleft and within two other regions of the receptor, termed meta-binding sites, defined by the extracellular loops. The first meta-binding site is located outside of the TM bundle, between EL2 and EL3, and the second higher energy site is positioned immediately underneath EL2. Binding at both the principal TM binding site and the lower energy meta-binding sites potentially affects the observed ligand potency. In meta-binding site I, the side chain of Glu209 (EL2) is within hydrogen-bonding distance (2.8 A) of the ribose O3', and Arg287 (EL3) coordinates both alpha- and beta-phosphates of the triphosphate chain, consistent with the insensitivity in potency of the 5'-monophosphate agonist, HT-AMP, to mutation of Arg287 to Lys. Moreover, the selective reduction in potency of 3'NH2-ATP in activating the E209R mutant receptor is consistent with the hypothesis of direct contact between EL2 and nucleotide ligands. Our findings support ATP binding to at least two distinct domains of the P2Y1 receptor, both outside and within the TM core. The two disulfide bridges present in the human P2Y1 receptor play a major role in the structure and stability of the receptor, to constrain the loops within the receptor, specifically stretching the EL2 over the opening of the TM cleft and thus defining the path of access to the binding site. JF - Biochemistry AU - Moro, S AU - Hoffmann, C AU - Jacobson, K A AD - Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0810, USA. Y1 - 1999/03/23/ PY - 1999 DA - 1999 Mar 23 SP - 3498 EP - 3507 VL - 38 IS - 12 SN - 0006-2960, 0006-2960 KW - Ligands KW - 0 KW - P2RY1 protein, human KW - Receptors, Purinergic P2 KW - Receptors, Purinergic P2Y1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Models, Molecular KW - Humans KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Protein Binding KW - Protein Conformation KW - Binding Sites KW - Receptors, Purinergic P2 -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Receptors, Purinergic P2 -- chemistry KW - GTP-Binding Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69650733?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Role+of+the+extracellular+loops+of+G+protein-coupled+receptors+in+ligand+recognition%3A+a+molecular+modeling+study+of+the+human+P2Y1+receptor.&rft.au=Moro%2C+S%3BHoffmann%2C+C%3BJacobson%2C+K+A&rft.aulast=Moro&rft.aufirst=S&rft.date=1999-03-23&rft.volume=38&rft.issue=12&rft.spage=3498&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-19 N1 - Date created - 1999-04-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phosphorothioate oligodeoxyribonucleotides inhibit ribonuclease L thereby disabling a mechanism of interferon action. AN - 69694049; 10206556 AB - Phosphorothioate oligodeoxyribonucleotides were found to be inhibitors of the 2-5A-dependent RNase L. Inhibitory potency depended upon the chain length of the phosphorothioate oligonucleotide and was dependent on the phosphorothioate substitution pattern, but was not substantially base-dependent. JF - Bioorganic & medicinal chemistry letters AU - Player, M R AU - Torrence, P F AD - Section on Biomedical Chemistry, Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0805, USA. Y1 - 1999/03/22/ PY - 1999 DA - 1999 Mar 22 SP - 891 EP - 894 VL - 9 IS - 6 SN - 0960-894X, 0960-894X KW - Oligodeoxyribonucleotides KW - 0 KW - Thionucleotides KW - Endoribonucleases KW - EC 3.1.- KW - 2-5A-dependent ribonuclease KW - EC 3.1.26.- KW - Index Medicus KW - Oligodeoxyribonucleotides -- chemistry KW - Humans KW - Oligodeoxyribonucleotides -- chemical synthesis KW - Models, Chemical KW - Inhibitory Concentration 50 KW - Thionucleotides -- pharmacology KW - Endoribonucleases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69694049?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Bioorganic+%26+medicinal+chemistry+letters&rft.atitle=Phosphorothioate+oligodeoxyribonucleotides+inhibit+ribonuclease+L+thereby+disabling+a+mechanism+of+interferon+action.&rft.au=Player%2C+M+R%3BTorrence%2C+P+F&rft.aulast=Player&rft.aufirst=M&rft.date=1999-03-22&rft.volume=9&rft.issue=6&rft.spage=891&rft.isbn=&rft.btitle=&rft.title=Bioorganic+%26+medicinal+chemistry+letters&rft.issn=0960894X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-22 N1 - Date created - 1999-06-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Reduced capacitative calcium entry correlates with vesicle accumulation and apoptosis. AN - 69622361; 10075732 AB - A preneoplastic variant of Syrian hamster embryo cells, sup(+), exhibits decreased endoplasmic reticulum calcium levels and subsequently undergoes apoptosis in low serum conditions (Preston, G. A., Barrett, J. C., Biermann, J. A., and Murphy, E. (1997) Cancer Res. 57, 537-542). This decrease in endoplasmic reticulum calcium appears to be due, at least in part, to reduced capacitative calcium entry at the plasma membrane. Thus we investigated whether inhibition of capacitative calcium entry per se could reduce endoplasmic reticulum calcium and induce apoptosis of cells. We find that treatment with either SKF96365 (30-100 microM) or cell-impermeant 1,2-bis(o-amino-5-bromophenoxy)ethane-N,N,N', N'-tetraacetic acid (5-10 mM) is able to induce apoptosis of cells in conditions where apoptosis does not normally occur. Because previous work has implicated vesicular trafficking as a mechanism of regulating capacitative calcium entry, we investigated whether disruption of vesicular trafficking could lead to decreased capacitative calcium entry and subsequent apoptosis of cells. Coincident with low serum-induced apoptosis, we observed an accumulation of vesicles within the cell, suggesting deregulated vesicle trafficking. Treatment of cells with bafilomycin (30-100 nM), an inhibitor of the endosomal proton ATPase, produced an accumulation of vesicles, decreased capacitative entry, and induced apoptosis. These data suggest that deregulation of vesicular transport results in reduced capacitative calcium entry which in turn results in apoptosis. JF - The Journal of biological chemistry AU - Jayadev, S AU - Petranka, J G AU - Cheran, S K AU - Biermann, J A AU - Barrett, J C AU - Murphy, E AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. jayadev@niehs.nih.gov Y1 - 1999/03/19/ PY - 1999 DA - 1999 Mar 19 SP - 8261 EP - 8268 VL - 274 IS - 12 SN - 0021-9258, 0021-9258 KW - Anti-Bacterial Agents KW - 0 KW - Calcium Channel Blockers KW - Calcium Channels KW - Imidazoles KW - Macrolides KW - bafilomycin A KW - 116764-51-3 KW - 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole KW - I61V87164A KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Organelles -- metabolism KW - Animals KW - Calcium Channels -- metabolism KW - Imidazoles -- pharmacology KW - Calcium Channel Blockers -- pharmacology KW - Cytoplasm -- metabolism KW - Hydrogen-Ion Concentration KW - Anti-Bacterial Agents -- pharmacology KW - Mesocricetus KW - DNA Fragmentation KW - Cell Line KW - Cricetinae KW - Calcium -- metabolism KW - Apoptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69622361?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Reduced+capacitative+calcium+entry+correlates+with+vesicle+accumulation+and+apoptosis.&rft.au=Jayadev%2C+S%3BPetranka%2C+J+G%3BCheran%2C+S+K%3BBiermann%2C+J+A%3BBarrett%2C+J+C%3BMurphy%2C+E&rft.aulast=Jayadev&rft.aufirst=S&rft.date=1999-03-19&rft.volume=274&rft.issue=12&rft.spage=8261&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The two amino acid substitutions in the L protein of cpts530/1009, a live-attenuated respiratory syncytial virus candidate vaccine, are independent temperature-sensitive and attenuation mutations. AN - 69674420; 10195777 AB - cpts530/1009 is a live-attenuated, temperature-sensitive (ts) RSV vaccine candidate that was shown previously to be attenuated for seronegative humans. It was generated by two rounds of chemical mutagenesis: first, a partially attenuated, cold-passaged (cp), non-ts RSV mutant (cpRSV) was mutagenized to yield the ts derivative cpts530, and then cpts530 was mutagenized to yield cpts530/1009, which is more ts. Previous nucleotide (nt) sequence analysis of cpts530 showed that it has a single nt change compared to cpRSV that results in an amino acid substitution at residue 521 in the L protein. Reverse genetics confirmed that this mutation is responsible for the ts phenotype of cpts530. Here, determination of the complete 15,222-nt sequence of cpts530/ 1009 identified a single change compared to cpts530, namely a point mutation at nt 12002, which results in a methionine-tovaline substitution at amino acid 1169 in the L protein. The contribution of the 1009 mutation to the level of temperature sensitivity and attenuation exhibited by cpts530/1009 was evaluated by its introduction alone or with the 530 and cp mutations into the full-length cDNA clone of wild-type (wt) RSV. Subsequent analysis of infectious viruses recovered from the mutant cDNAs indicated that (i) the 1009 mutation indeed was a ts mutation and the level of temperature sensitivity specified by the 1009 mutation was less than that specified by the 530 mutation, (ii) the 530 and 1009 mutations each contributed to attenuation in the upper respiratory tract of mice and their effects were additive, (iii) viruses bearing the 1009 mutation were more attenuated in the lower respiratory tract of mice than viruses bearing the 530 mutation and (iv) the combination of the 530 and 1009 mutations in the cpRSV background resulted in the same level of temperature sensitivity and attenuation in mice as that observed for the biologically-derived cpts530/1009 mutant. These data show that the genetic basis of the attenuation and temperature sensitivity of the cpts530/1009 candidate vaccine virus is the sum of the contributions of seven identified amino acid substitutions, i.e. the 5 cpRSV mutations, the 530 mutation and the 1009 mutation. JF - Vaccine AU - Juhasz, K AU - Whitehead, S S AU - Boulanger, C A AU - Firestone, C Y AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-0720, USA. Y1 - 1999/03/17/ PY - 1999 DA - 1999 Mar 17 SP - 1416 EP - 1424 VL - 17 IS - 11-12 SN - 0264-410X, 0264-410X KW - HN Protein KW - 0 KW - RNA, Viral KW - Vaccines, Attenuated KW - Viral Envelope Proteins KW - Viral Proteins KW - Viral Vaccines KW - attachment protein G KW - Index Medicus KW - Animals KW - Humans KW - Respiratory Syncytial Viruses KW - Temperature KW - Mice KW - Mice, Inbred BALB C KW - Structure-Activity Relationship KW - Mutagenesis, Site-Directed KW - Phenotype KW - Transfection KW - Sequence Analysis KW - Cercopithecus aethiops KW - RNA, Viral -- chemistry KW - Vero Cells KW - Amino Acid Substitution KW - Viral Proteins -- immunology KW - Viral Proteins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69674420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=The+two+amino+acid+substitutions+in+the+L+protein+of+cpts530%2F1009%2C+a+live-attenuated+respiratory+syncytial+virus+candidate+vaccine%2C+are+independent+temperature-sensitive+and+attenuation+mutations.&rft.au=Juhasz%2C+K%3BWhitehead%2C+S+S%3BBoulanger%2C+C+A%3BFirestone%2C+C+Y%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Juhasz&rft.aufirst=K&rft.date=1999-03-17&rft.volume=17&rft.issue=11-12&rft.spage=1416&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-08 N1 - Date created - 1999-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Methionine residues may protect proteins from critical oxidative damage. AN - 69803363; 10360685 AB - Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they form disulfide bonds which contribute to protein structure. In contrast, the key functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, providing for efficient scavenging of oxidants. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the sixteen methionine residues could be oxidized with little effect on activity. The oxidizable methionine residues were found to be relatively surface exposed while the intact residues were generally buried within the core of the protein. Further, the susceptible residues were physically arranged in an array which guarded the entrance to the active site. Methionine sulfoxide can be reduced back to methionine by the enzyme methionine sulfoxide reductase, providing a catalytic amplification of the antioxidant potential of each methionine residue. Given the importance of oxidative stress during aging, the potential function of methionine residues as antioxidants during aging should be investigated experimentally. JF - Mechanisms of ageing and development AU - Levine, R L AU - Berlett, B S AU - Moskovitz, J AU - Mosoni, L AU - Stadtman, E R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-0320, USA. rlevine@nih.gov Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 323 EP - 332 VL - 107 IS - 3 SN - 0047-6374, 0047-6374 KW - Antioxidants KW - 0 KW - Oxidants KW - Proteins KW - Methionine KW - AE28F7PNPL KW - Hydrogen Peroxide KW - BBX060AN9V KW - Oxidoreductases KW - EC 1.- KW - Methionine Sulfoxide Reductases KW - EC 1.8.4.- KW - methionine sulfoxide reductase KW - EC 1.8.4.11 KW - Endopeptidases KW - EC 3.4.- KW - Glutamate-Ammonia Ligase KW - EC 6.3.1.2 KW - methionine sulfoxide KW - XN1XVI4B2C KW - Index Medicus KW - Oxidation-Reduction KW - Glutamate-Ammonia Ligase -- metabolism KW - Oxidoreductases -- metabolism KW - Oxidants -- pharmacology KW - Hydrogen Peroxide -- metabolism KW - Hydrogen Peroxide -- pharmacology KW - Endopeptidases -- metabolism KW - Oxidants -- metabolism KW - Antioxidants -- metabolism KW - Methionine -- metabolism KW - Methionine -- analogs & derivatives KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69803363?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Mechanisms+of+ageing+and+development&rft.atitle=Methionine+residues+may+protect+proteins+from+critical+oxidative+damage.&rft.au=Levine%2C+R+L%3BBerlett%2C+B+S%3BMoskovitz%2C+J%3BMosoni%2C+L%3BStadtman%2C+E+R&rft.aulast=Levine&rft.aufirst=R&rft.date=1999-03-15&rft.volume=107&rft.issue=3&rft.spage=323&rft.isbn=&rft.btitle=&rft.title=Mechanisms+of+ageing+and+development&rft.issn=00476374&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-03 N1 - Date created - 1999-08-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Fas-mediated suicide of tumor-reactive T cells following activation by specific tumor: selective rescue by caspase inhibition. AN - 69646730; 10092779 AB - CD8+ T lymphocytes that specifically recognize tumor cells can be isolated and expanded ex vivo. While the lytic properties of these cells have been well described, their fate upon encounter with cognate tumor is not known. We performed reverse 51Cr release assays in which the lymphocyte effectors rather than the tumor cell targets were radioactively labeled. We found that melanoma tumor cells caused the apoptotic death of tumor-specific T cells only upon specific MHC class I-restricted recognition. This death was entirely blockable by the addition of an Ab directed against the Fas death receptor (APO-1, CD95). Contrary to the prevailing view that tumor cells cause the death of anti-tumor T cells by expressing Fas ligand (FasL), our data suggested that FasL was instead expressed by T lymphocytes upon activation. While the tumor cells did not express FasL by any measure (including RT-PCR), functional FasL (as well as FasL mRNA) was consistently found on activated anti-tumor T cells. We could successfully block the activation-induced cell death with z-VAD-fmk, a tripeptide inhibitor of IL-1 beta-converting enzyme homologues, or with anti-Fas mAbs. Most importantly, these interventions did not inhibit T cell recognition as measured by IFN-gamma release, nor did they adversely affect the specific lysis of tumor cell targets. These results imply that Fas-mediated activation-induced cell death could be a limiting factor in the in vivo efficacy of adoptive transfer of class I-restricted CD8+ T cells and provide a means of potentially enhancing their growth in vitro as well as their function in vivo. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Zaks, T Z AU - Chappell, D B AU - Rosenberg, S A AU - Restifo, N P AD - Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA. zakst@nih.gov Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 3273 EP - 3279 VL - 162 IS - 6 SN - 0022-1767, 0022-1767 KW - Antigens, CD95 KW - 0 KW - Caspase Inhibitors KW - Cysteine Proteinase Inhibitors KW - Epitopes, T-Lymphocyte KW - FASLG protein, human KW - Fas Ligand Protein KW - Membrane Glycoproteins KW - Receptors, Antigen, T-Cell KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Cysteine Proteinase Inhibitors -- pharmacology KW - Cytotoxicity, Immunologic KW - CD8-Positive T-Lymphocytes -- pathology KW - Tumor Cells, Cultured KW - Membrane Glycoproteins -- physiology KW - CD8-Positive T-Lymphocytes -- metabolism KW - CD8-Positive T-Lymphocytes -- immunology KW - Humans KW - Receptors, Antigen, T-Cell -- metabolism KW - Cytotoxicity Tests, Immunologic KW - Epitopes, T-Lymphocyte -- biosynthesis KW - Lymphocytes, Tumor-Infiltrating -- immunology KW - Lymphocyte Activation -- immunology KW - Melanoma -- enzymology KW - Antigens, CD95 -- physiology KW - Antigens, CD95 -- biosynthesis KW - Lymphocytes, Tumor-Infiltrating -- pathology KW - Apoptosis -- immunology KW - Melanoma -- immunology KW - Melanoma -- metabolism KW - Lymphocytes, Tumor-Infiltrating -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69646730?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Fas-mediated+suicide+of+tumor-reactive+T+cells+following+activation+by+specific+tumor%3A+selective+rescue+by+caspase+inhibition.&rft.au=Zaks%2C+T+Z%3BChappell%2C+D+B%3BRosenberg%2C+S+A%3BRestifo%2C+N+P&rft.aulast=Zaks&rft.aufirst=T&rft.date=1999-03-15&rft.volume=162&rft.issue=6&rft.spage=3273&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Immunol. 1998 Aug 1;161(3):1220-30 [9686582] Cancer Res. 1999 Jan 1;59(1):59-62 [9892185] EMBO J. 1997 Jul 1;16(13):3805-12 [9233790] J Immunol Methods. 1987 Aug 24;102(1):127-41 [3305708] Nature. 1991 Oct 31;353(6347):858-61 [1944559] J Exp Med. 1993 Jan 1;177(1):195-200 [7678113] Cancer. 1994 Mar 15;73(6):1731-7 [8156501] J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66 [8028037] Nature. 1995 Feb 2;373(6513):438-41 [7530335] Nature. 1995 Feb 2;373(6513):441-4 [7530336] Nature. 1995 Feb 2;373(6513):444-8 [7530337] Br J Cancer. 1995 Feb;71(2):240-5 [7841036] J Immunol. 1995 Apr 15;154(8):3961-8 [7706734] Cell. 1995 Jun 16;81(6):935-46 [7540117] Nature. 1995 Oct 5;377(6548):446-8 [7566124] Curr Biol. 1996 Jul 1;6(7):897-9 [8805307] Science. 1996 Nov 22;274(5291):1363-6 [8910274] J Exp Med. 1996 Nov 1;184(5):2067-72 [8920897] J Exp Med. 1996 Dec 1;184(6):2445-50 [8976202] Br J Haematol. 1997 Jan;96(1):147-57 [9012700] Immunity. 1997 Feb;6(2):209-15 [9047242] Cancer Res. 1997 Mar 15;57(6):1007-12 [9067260] Semin Immunol. 1997 Feb;9(1):1-5 [9106302] Semin Immunol. 1997 Feb;9(1):35-49 [9106306] Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6420-5 [9177233] J Exp Med. 1997 Dec 1;186(11):1939-44 [9382892] J Exp Med. 1998 Feb 16;187(4):587-600 [9463409] J Exp Med. 1998 Apr 20;187(8):1205-13 [9547332] J Immunol. 1998 May 1;160(9):4159-60 [9574514] Cancer J Sci Am. 1998 Mar-Apr;4(2):86-93 [9532410] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Integrity of human YACs during propagation in recombination-deficient yeast strains. AN - 69641953; 10087193 AB - Several isogenic strains with defects in recombination/repair genes (RAD1, RAD50, RAD51, RAD52, RAD54, and RAD55) were examined for their ability to propagate accurately a variety of linear and circular yeast artificial chromosomes (YACs) containing human DNA inserts. To assess YAC stability, the human DNA inserts were internally marked by an ADE2-pBR-URA3 cassette. Following selection for Ura- clones on 5-fluoroorotic acid containing medium, the following types of YAC deletions were identified: (i) those caused by homologous recombination with a telomeric pBR sequence; (ii) internal deletions, presumed to occur by recombination between commonly occurring DNA repeats such as Alu and LINE sequences; and (iii) deletions leading to loss of part of a YAC arm. rad52 host strains, but not other recombination-deficient strains, decreased the rate of all types of YAC deletions 25- to 400-fold. We have also developed and tested kar1 strains with a conditional RAD52 gene that allow transfer of a YAC from any host into a recombination-deficient background. These strains provide an efficient tool for stabilization of YACs and are useful for allowing additional recombinational modification of YACs. Copyright 1999 Academic Press. JF - Genomics AU - Kouprina, N AU - Nikolaishvili, N AU - Graves, J AU - Koriabine, M AU - Resnick, M A AU - Larionov, V AD - Laboratory of Molecular Genetics, NIEHS, Research Triangle Park, North Carolina, 27709, USA. Kouprina@niehs.nih.gov Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 262 EP - 273 VL - 56 IS - 3 SN - 0888-7543, 0888-7543 KW - DNA Primers KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - RAD50 protein, S cerevisiae KW - RAD55 protein, S cerevisiae KW - Rad52 DNA Repair and Recombination Protein KW - Saccharomyces cerevisiae Proteins KW - RAD51 protein, human KW - EC 2.7.7.- KW - Rad51 Recombinase KW - Endonucleases KW - EC 3.1.- KW - RAD1 protein, S cerevisiae KW - RAD54 protein, S cerevisiae KW - EC 3.6.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - DNA Repair Enzymes KW - EC 6.5.1.- KW - Glucose KW - IY9XDZ35W2 KW - Galactose KW - X2RN3Q8DNE KW - Index Medicus KW - Endonucleases -- physiology KW - Fungal Proteins -- physiology KW - Glucose -- metabolism KW - Humans KW - Yeasts -- genetics KW - Galactose -- metabolism KW - Fungal Proteins -- genetics KW - Models, Biological KW - Chromosome Mapping KW - Gene Deletion KW - Genotype KW - Transformation, Genetic KW - Mitosis -- genetics KW - Mutagenesis, Insertional KW - Chromosomes, Artificial, Yeast -- physiology KW - DNA-Binding Proteins -- genetics KW - DNA-Binding Proteins -- physiology KW - Chromosomes, Artificial, Yeast -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69641953?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Genomics&rft.atitle=Integrity+of+human+YACs+during+propagation+in+recombination-deficient+yeast+strains.&rft.au=Kouprina%2C+N%3BNikolaishvili%2C+N%3BGraves%2C+J%3BKoriabine%2C+M%3BResnick%2C+M+A%3BLarionov%2C+V&rft.aulast=Kouprina&rft.aufirst=N&rft.date=1999-03-15&rft.volume=56&rft.issue=3&rft.spage=262&rft.isbn=&rft.btitle=&rft.title=Genomics&rft.issn=08887543&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-24 N1 - Date created - 1999-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conserved bipartite motifs in yeast eIF5 and eIF2Bepsilon, GTPase-activating and GDP-GTP exchange factors in translation initiation, mediate binding to their common substrate eIF2. AN - 69624570; 10075937 AB - In the initiation phase of eukaryotic translation, eIF5 stimulates the hydrolysis of GTP bound to eIF2 in the 40S ribosomal pre-initiation complex, and the resultant GDP on eIF2 is replaced with GTP by the complex nucleotide exchange factor, eIF2B. Bipartite motifs rich in aromatic and acidic residues are conserved at the C-termini of eIF5 and the catalytic (epsilon) subunit of eIF2B. Here we show that these bipartite motifs are important for the binding of these factors, both in vitro and in vivo, to the beta subunit of their common substrate eIF2. We also find that three lysine-rich boxes in the N-terminal segment of eIF2beta mediate the binding of eIF2 to both eIF5 and eIF2B. Thus, eIF5 and eIF2Bepsilon employ the same sequence motif to facilitate interaction with the same segment of their common substrate. In agreement with this, archaea appear to lack eIF5, eIF2B and the lysine-rich binding domain for these factors in their eIF2beta homolog. The eIF5 bipartite motif is also important for its interaction with the eIF3 complex through the NIP1-encoded subunit of eIF3. Thus, the bipartite motif in eIF5 appears to be multifunctional, stimulating its recruitment to the 40S pre-initiation complex through interaction with eIF3 in addition to binding of its substrate eIF2. JF - The EMBO journal AU - Asano, K AU - Krishnamoorthy, T AU - Phan, L AU - Pavitt, G D AU - Hinnebusch, A G AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 1673 EP - 1688 VL - 18 IS - 6 SN - 0261-4189, 0261-4189 KW - Eukaryotic Initiation Factor-2 KW - 0 KW - Eukaryotic Initiation Factor-2B KW - Eukaryotic Initiation Factor-5 KW - GTPase-Activating Proteins KW - Guanine Nucleotide Exchange Factors KW - Macromolecular Substances KW - Peptide Initiation Factors KW - Proteins KW - Recombinant Proteins KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine Triphosphate KW - 86-01-1 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Index Medicus KW - Animals KW - Guanosine Diphosphate -- metabolism KW - Humans KW - Amino Acid Sequence KW - Cloning, Molecular KW - Guanosine Triphosphate -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Recombinant Proteins -- chemistry KW - Sequence Homology, Amino Acid KW - Drosophila -- genetics KW - Peptide Initiation Factors -- metabolism KW - Peptide Initiation Factors -- genetics KW - Proteins -- chemistry KW - Peptide Chain Initiation, Translational KW - GTP-Binding Proteins -- metabolism KW - GTP-Binding Proteins -- chemistry KW - Eukaryotic Initiation Factor-2 -- metabolism KW - Peptide Initiation Factors -- chemistry KW - Eukaryotic Initiation Factor-2 -- chemistry KW - Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69624570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+EMBO+journal&rft.atitle=Conserved+bipartite+motifs+in+yeast+eIF5+and+eIF2Bepsilon%2C+GTPase-activating+and+GDP-GTP+exchange+factors+in+translation+initiation%2C+mediate+binding+to+their+common+substrate+eIF2.&rft.au=Asano%2C+K%3BKrishnamoorthy%2C+T%3BPhan%2C+L%3BPavitt%2C+G+D%3BHinnebusch%2C+A+G&rft.aulast=Asano&rft.aufirst=K&rft.date=1999-03-15&rft.volume=18&rft.issue=6&rft.spage=1673&rft.isbn=&rft.btitle=&rft.title=The+EMBO+journal&rft.issn=02614189&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-25 N1 - Date created - 1999-05-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1970 Aug 15;227(5259):680-5 [5432063] J Biol Chem. 1982 Sep 25;257(18):10846-51 [7050121] Proc Natl Acad Sci U S A. 1987 Jul;84(14):4767-71 [3474623] Methods Enzymol. 1987;154:164-75 [3323810] Cell. 1988 Aug 26;54(5):621-32 [3136928] Cell. 1988 Aug 26;54(5):633-9 [3044606] Gene. 1988 Jul 15;67(1):31-40 [3047011] Gene. 1988 Dec 30;74(2):527-34 [3073106] Genetics. 1989 May;122(1):19-27 [2659436] Methods Enzymol. 1991;194:428-53 [2005802] Mol Cell Biol. 1991 Jun;11(6):3217-28 [2038327] Mol Cell Biol. 1992 Jan;12(1):248-60 [1729602] Gene. 1992 Jan 2;110(1):119-22 [1544568] Mol Cell Biol. 1993 Jan;13(1):506-20 [8417348] Mol Cell Biol. 1993 Mar;13(3):1920-32 [8441423] Mol Cell Biol. 1993 Aug;13(8):4618-31 [8336705] Biochemistry. 1994 Apr 26;33(16):4794-9 [8161539] J Biol Chem. 1994 Dec 23;269(51):32286-92 [7798228] J Biol Chem. 1995 Mar 3;270(9):4288-92 [7876188] FEBS Lett. 1995 May 22;365(1):47-50 [7774713] J Biol Chem. 1995 Sep 15;270(37):21975-83 [7665619] Mol Cell Biol. 1995 Nov;15(11):6351-63 [7565788] Protein Sci. 1995 Aug;4(8):1608-17 [8520487] Mol Cell Biol. 1996 May;16(5):2307-13 [8628297] Science. 1996 Aug 23;273(5278):1058-73 [8688087] Mol Cell Biol. 1996 Nov;16(11):6603-16 [8887689] Mol Cell Biol. 1997 Mar;17(3):1298-313 [9032257] Mol Cell Biol. 1997 Jul;17(7):4146-58 [9199350] J Biol Chem. 1997 Jul 18;272(29):18333-40 [9218474] J Biol Chem. 1997 Aug 29;272(35):21661-4 [9268289] Genes Dev. 1997 Sep 15;11(18):2396-413 [9308967] J Biol Chem. 1997 Oct 24;272(43):27042-52 [9341143] EMBO J. 1997 Nov 17;16(22):6812-22 [9362495] J Bacteriol. 1997 Nov;179(22):7135-55 [9371463] Mol Cell Biol. 1997 Dec;17(12):6940-7 [9372926] Nature. 1997 Nov 27;390(6658):364-70 [9389475] J Biol Chem. 1997 Dec 12;272(50):31712-8 [9395514] Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):224-8 [9419357] J Biol Chem. 1998 Jan 30;273(5):3039-44 [9446619] Genes Dev. 1998 Feb 15;12(4):514-26 [9472020] Mol Cell Biol. 1998 May;18(5):2697-711 [9566889] Science. 1998 Jun 12;280(5370):1757-60 [9624054] J Biol Chem. 1998 Jul 17;273(29):18573-85 [9660829] Mol Cell Biol. 1998 Aug;18(8):4935-46 [9671501] J Biol Chem. 1998 Sep 4;273(36):23485-94 [9722586] Nature. 1998 Aug 27;394(6696):854-9 [9732867] Genes Dev. 1998 Dec 1;12(23):3650-62 [9851972] Erratum In: EMBO J 1999 May 4;18(9):2670 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Hepatitis B virus X protein inhibits nucleotide excision repair. AN - 69615371; 10074921 AB - Human hepatitis B virus (HBV) is a major risk factor of human hepatocellular carcinoma. Both in vivo and in vitro studies have shown that HBV X protein (HBx) can bind to the p53 tumor-suppressor protein and interfere with the role that p53 plays in the cellular response to DNA damage. Our previous work has shown that HBx protein inhibits p53 sequence-specific transcriptional activation, p53-mediated apoptosis and p53 binding to the TFIIH transcription-nucleotide excision repair (NER) factors, including XPB and XPD. To investigate whether HBx interferes with the NER pathway, we utilized cell-proliferation and colony-formation assays to determine if cells expressing HBx are more sensitive to UVC-induced DNA damage. NER was also measured by a plasmid host cell re-activation assay using a vector containing a luciferase reporter gene. UV-irradiated plasmids were transfected into a human RKO colon carcinoma cell line that contains wild-type (wt) p53 as well as its derivatives, either mutant p53-143ala (RKO-143ala) or human papillomavirus E6 (RKO-E6, a wt p53 protein that is rapidly degraded and non-functional). We found that cells expressing HBx are more sensitive to UVC-induced killing. Moreover, expression of HBx resulted in a reduction of NER efficiency in RKO cells to 52 +/- 2% (compared with control), RKO-143a1a cells to 46 +/- 3% and RKO-E6 cells to 60 +/- 3%. Similar results were also obtained with a HepG2 hepatoblastoma cell line carrying wt p53. In addition, we found that HBx bound directly to either XPB or XPD DNA helicase in vitro. Thus, our data indicate that HBx may interfere with the NER pathway through both p53-dependent and p53-independent mechanisms. Because HBx binds to TFIIH-associated proteins, we propose that HBx may interfere with the NER pathway also through binding to and altering the activities of helicases necessary for NER and, thereby, increase the mutation rate induced by chemical carcinogens, such as aflatoxin B1, during human liver carcinogenesis. JF - International journal of cancer AU - Jia, L AU - Wang, X W AU - Harris, C C AD - Laboratory of Human Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 875 EP - 879 VL - 80 IS - 6 SN - 0020-7136, 0020-7136 KW - Carcinogens KW - 0 KW - DNA-Binding Proteins KW - Proteins KW - Recombinant Fusion Proteins KW - Trans-Activators KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - hepatitis B virus X protein KW - XPBC-ERCC-3 protein KW - 146045-44-5 KW - DNA Helicases KW - EC 3.6.4.- KW - Xeroderma Pigmentosum Group D Protein KW - EC 3.6.4.12 KW - ERCC2 protein, human KW - EC 5.99.- KW - Index Medicus KW - Ultraviolet Rays KW - Apoptosis KW - DNA Damage KW - DNA Helicases -- antagonists & inhibitors KW - Humans KW - Radiation Tolerance KW - Transcription, Genetic KW - Mutagenesis KW - Recombinant Fusion Proteins -- physiology KW - Genes, p53 KW - Genes, Reporter KW - Colonic Neoplasms -- pathology KW - Tumor Stem Cell Assay KW - Cell Division KW - Carcinoma -- genetics KW - DNA-Binding Proteins -- metabolism KW - Tumor Suppressor Protein p53 -- biosynthesis KW - Colonic Neoplasms -- genetics KW - Cocarcinogenesis KW - DNA Helicases -- metabolism KW - Carcinogens -- pharmacokinetics KW - Proteins -- metabolism KW - Tumor Cells, Cultured -- radiation effects KW - Proteins -- antagonists & inhibitors KW - Carcinoma -- pathology KW - Transfection KW - DNA-Binding Proteins -- antagonists & inhibitors KW - Carcinogens -- adverse effects KW - DNA Repair KW - Hepatitis B virus -- genetics KW - Hepatitis B virus -- physiology KW - Hepatitis B -- complications KW - Liver Neoplasms -- pathology KW - Carcinoma, Hepatocellular -- etiology KW - Trans-Activators -- genetics KW - Carcinoma, Hepatocellular -- genetics KW - Carcinoma, Hepatocellular -- pathology KW - Trans-Activators -- physiology KW - Liver Neoplasms -- etiology KW - Liver Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69615371?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+journal+of+cancer&rft.atitle=Hepatitis+B+virus+X+protein+inhibits+nucleotide+excision+repair.&rft.au=Jia%2C+L%3BWang%2C+X+W%3BHarris%2C+C+C&rft.aulast=Jia&rft.aufirst=L&rft.date=1999-03-15&rft.volume=80&rft.issue=6&rft.spage=875&rft.isbn=&rft.btitle=&rft.title=International+journal+of+cancer&rft.issn=00207136&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Role of protein kinase A in the maintenance of inflammatory pain. AN - 69607946; 10066271 AB - Although the initiation of inflammatory pain (hyperalgesia) has been demonstrated to require the cAMP second messenger signaling cascade, whether this mechanism and/or other mechanisms underlie the continued maintenance of the induced hyperalgesia is unknown. We report that injection of adenylyl cyclase inhibitors before but not after injection of direct-acting hyperalgesic agents (prostaglandin E2 and purine and serotonin receptor agonists) resulted in reduction in hyperalgesia, evaluated by the Randall-Selitto paw-withdrawal test. In contrast, injection of protein kinase A (PKA) inhibitors either before or after these hyperalgesic agents resulted in reduced hyperalgesia, suggesting that hyperalgesia after its activation was maintained by persistent PKA activity but not by adenylyl cyclase activity. To evaluate further the role of PKA activity in the maintenance of hyperalgesia, we injected the catalytic subunit of PKA (PKACS) that resulted in hyperalgesia similar in magnitude to that induced by the direct-acting hyperalgesic agents but much longer in duration (>48 vs 2 hr). Injection of WIPTIDE (a PKA inhibitor) at 24 hr after PKACS reduced hyperalgesia, suggesting that PKACS hyperalgesia is not independently maintained by steps downstream from PKA. In summary, our results indicate that, once established, inflammatory mediator-induced hyperalgesia is no longer maintained by adenylyl cyclase activity but rather is dependent on ongoing PKA activity. An understanding of the mechanism maintaining hyperalgesia may provide important insight into targets for the treatment of persistent pain. JF - The Journal of neuroscience : the official journal of the Society for Neuroscience AU - Aley, K O AU - Levine, J D AD - Departments of Anatomy, Medicine, and Oral Surgery, Neuroscience and Biomedical Sciences Graduate Programs, National Institutes of Health Pain Center, University of California, San Francisco, California 94143-0440, USA. Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 2181 EP - 2186 VL - 19 IS - 6 SN - 0270-6474, 0270-6474 KW - Adenylyl Cyclase Inhibitors KW - 0 KW - Enzyme Inhibitors KW - Phenethylamines KW - Serotonin Receptor Agonists KW - 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine KW - 120225-54-9 KW - 8-Hydroxy-2-(di-n-propylamino)tetralin KW - 78950-78-4 KW - Cyclic AMP-Dependent Protein Kinases KW - EC 2.7.11.11 KW - Adenosine KW - K72T3FS567 KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Serotonin Receptor Agonists -- pharmacology KW - Animals KW - Dinoprostone -- pharmacology KW - Drug Administration Schedule KW - Enzyme Inhibitors -- administration & dosage KW - Adenosine -- analogs & derivatives KW - Hindlimb -- drug effects KW - Nociceptors -- drug effects KW - Rats KW - Injections, Intradermal KW - Rats, Sprague-Dawley KW - Adenosine -- pharmacology KW - 8-Hydroxy-2-(di-n-propylamino)tetralin -- pharmacology KW - Pain Threshold -- drug effects KW - Enzyme Inhibitors -- pharmacology KW - Phenethylamines -- pharmacology KW - Male KW - Dinoprostone -- antagonists & inhibitors KW - Cyclic AMP-Dependent Protein Kinases -- physiology KW - Hyperalgesia -- physiopathology KW - Cyclic AMP-Dependent Protein Kinases -- antagonists & inhibitors KW - Hyperalgesia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607946?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.atitle=Role+of+protein+kinase+A+in+the+maintenance+of+inflammatory+pain.&rft.au=Aley%2C+K+O%3BLevine%2C+J+D&rft.aulast=Aley&rft.aufirst=K&rft.date=1999-03-15&rft.volume=19&rft.issue=6&rft.spage=2181&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+neuroscience+%3A+the+official+journal+of+the+Society+for+Neuroscience&rft.issn=02706474&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Differential Sensitivity of Distinct Chlamydia trachomatis Isolates to IFN- gamma -Mediated Inhibition AN - 17201436; 4495144 AB - Resistance to the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis has been mapped to MHC class II-restricted, IL-12-dependent CD4 super(+) T cells that secrete a type 1 profile of proinflammatory cytokines, which includes IFN- gamma and TNF- alpha . The relative contribution of IFN- gamma is controversial, however, due to variation in results presented by different laboratories. To determine whether C. trachomatis strain differences contributed to this apparent conflict, the relative resistance of IFN- gamma -deficient mice to murine and human strains of C. trachomatis was compared. All human serovars were much more sensitive to the direct inhibitory actions of IFN- gamma than the MoPn strain. Furthermore, genital clearance of human serovar D in the C57BL/6 mouse was mediated by class II-independent mechanisms that probably involved local production of IFN- gamma by cells of the innate immune system. TNF- alpha also contributed indirectly to host resistance against all strains tested. The differential susceptibility of distinct C. trachomatis strains to effector cytokines such as IFN gamma could not have been predicted by interstrain biologic variation or by the profile of cytokines stimulated during infection. These findings indicate that strain variation should be considered in situations where related isolates of a given parasite produce conflicting data in models of infection and immunity. They also suggest that stimulation of mucosal IFN- gamma activity is a relevant goal for a human chlamydial vaccine. JF - Journal of Immunology AU - Perry, L L AU - Su, H AU - Feilzer, K AU - Messer, R AU - Hughes, S AU - Whitmire, W AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratory, 903 South 4th Street, Hamilton, MT 59840, USA, hcaldwell@atlas.niaid.nih.gov Y1 - 1999/03/15/ PY - 1999 DA - 1999 Mar 15 SP - 3541 EP - 3548 VL - 162 IS - 6 SN - 0022-1767, 0022-1767 KW - Chlamydia trachomatis KW - mice KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Mucosal immunity KW - Pneumonitis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17201436?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Differential+Sensitivity+of+Distinct+Chlamydia+trachomatis+Isolates+to+IFN-+gamma+-Mediated+Inhibition&rft.au=Perry%2C+L+L%3BSu%2C+H%3BFeilzer%2C+K%3BMesser%2C+R%3BHughes%2C+S%3BWhitmire%2C+W%3BCaldwell%2C+H+D&rft.aulast=Perry&rft.aufirst=L&rft.date=1999-03-15&rft.volume=162&rft.issue=6&rft.spage=3541&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Mucosal immunity; Pneumonitis ER - TY - JOUR T1 - Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits. AN - 69609011; 10064831 AB - Sensitization of striatal N-methyl-d-aspartate (NMDA) receptors has been implicated in the pathogenesis of the response alterations associated with dopaminomimetic treatment of parkinsonian animals and patients. To determine whether serine phosphorylation of NMDA receptor subunits by activation of Ca2+/calmodulin-dependent protein-kinase II (CaMKII) contributes to this process, we examined the effects of unilateral nigrostriatal ablation with 6-hydroxydopamine and subsequent treatment with levodopa, SKF 38393 (D1-preferring dopamine agonist), or quinpirole (D2-preferring agonist) on motor responses and phosphorylation states. Three weeks of twice-daily levodopa administration to rats shortened the duration of their rotational response to levodopa or SKF 38393 challenge, but prolonged the duration of quinpirole-induced rotation. At the same time, levodopa treatment elevated serine phosphorylation of striatal NR2A (p<0.02), but not that of NR2B subunits, without associated changes in subunit protein levels. Chronic treatment with SKF 38393 increased NR2A (p<0.0001) but decreased NR2B (p<0.004) serine phosphorylation. In contrast, chronic quinpirole treatment had no effect on NR2A but increased NR2B phosphorylation (p<0.0001). The acute intrastriatal injection of the CaMKII inhibitor KN93 (1.0 micrograms) not only normalized the levodopa-induced motor response alterations but also attenuated the D1 and D2 receptor-mediated serine phosphorylation of NR2A and NR2B subunits, respectively (p<0.02). These results suggest that a CaMKII-mediated rise in serine phosphorylation of NMDA receptor subunits induced by intermittent stimulation of D1 or D2 dopaminergic receptors contributes to the apparent enhancement in striatal NMDA receptor sensitivity and thus to the dopaminergic response plasticity in levodopa-treated parkinsonian rats. Copyright 1999 Elsevier Science B.V. JF - Brain research AU - Oh, J D AU - Vaughan, C L AU - Chase, T N AD - Experimental Therapeutics Branch, Building 10, Room 5C103, National Institute of Neurological Disorders and Stroke, NIH, 90900 Rockville Pike, Bethesda, MD 20892, USA. Y1 - 1999/03/13/ PY - 1999 DA - 1999 Mar 13 SP - 433 EP - 442 VL - 821 IS - 2 SN - 0006-8993, 0006-8993 KW - Antibodies KW - 0 KW - Antiparkinson Agents KW - Benzylamines KW - Dopamine Agonists KW - Enzyme Inhibitors KW - Receptors, N-Methyl-D-Aspartate KW - Sulfonamides KW - Sympatholytics KW - KN 93 KW - 139298-40-1 KW - Phosphoserine KW - 17885-08-4 KW - Serine KW - 452VLY9402 KW - Levodopa KW - 46627O600J KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine KW - 67287-49-4 KW - Oxidopamine KW - 8HW4YBZ748 KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2 KW - EC 2.7.11.17 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Benzylamines -- pharmacology KW - Phosphoserine -- immunology KW - Parkinson Disease, Secondary -- chemically induced KW - Animals KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Motor Neurons -- enzymology KW - Phosphoserine -- analysis KW - Phosphoserine -- metabolism KW - Serine -- metabolism KW - Motor Neurons -- chemistry KW - Parkinson Disease, Secondary -- drug therapy KW - Rats KW - Levodopa -- pharmacology KW - Parkinson Disease, Secondary -- metabolism KW - Rats, Sprague-Dawley KW - Phosphorylation KW - Sulfonamides -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Antiparkinson Agents -- pharmacology KW - Male KW - Corpus Striatum -- cytology KW - Corpus Striatum -- chemistry KW - Nerve Degeneration -- metabolism KW - Dopamine Agonists -- pharmacology KW - Corpus Striatum -- metabolism KW - Dopamine -- physiology KW - Receptors, N-Methyl-D-Aspartate -- metabolism KW - 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69609011?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Effect+of+dopamine+denervation+and+dopamine+agonist+administration+on+serine+phosphorylation+of+striatal+NMDA+receptor+subunits.&rft.au=Oh%2C+J+D%3BVaughan%2C+C+L%3BChase%2C+T+N&rft.aulast=Oh&rft.aufirst=J&rft.date=1999-03-13&rft.volume=821&rft.issue=2&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Up-regulation of the Pit-2 phosphate transporter/retrovirus receptor by protein kinase C epsilon. AN - 69605165; 10066763 AB - The membrane receptors for the gibbon ape leukemia retrovirus and the amphotropic murine retrovirus serve normal cellular functions as sodium-dependent phosphate transporters (Pit-1 and Pit-2, respectively). Our earlier studies established that activation of protein kinase C (PKC) by treatment of cells with phorbol 12-myristate 13-acetate (PMA) enhanced sodium-dependent phosphate (Na/Pi) uptake. Studies now have been carried out to determine which type of Na/Pi transporter (Pit-1 or Pit-2) is regulated by PKC and which PKC isotypes are involved in the up-regulation of Na/Pi uptake by the Na/Pi transporter/viral receptor. It was found that the activation of short term (2-min) Na/Pi uptake by PMA is abolished when cells are infected with amphotropic murine retrovirus (binds Pit-2 receptor) but not with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating that Pit-2 is the form of Na/Pi transporter/viral receptor regulated by PKC. The PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan-PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype inhibitor Gö 6976, suggesting that a novel PKC isotype is required to regulate Pit-2. Overexpression of PKCepsilon, but not of PKCalpha, -delta, or -zeta, was found to mimic the activation of Na/Pi uptake. To further establish that PKCepsilon is involved in the regulation of Pit-2, cells were treated with PKCepsilon-selective antisense oligonucleotides. Treatment with PKCepsilon antisense oligonucleotides decreased the PMA-induced activation of Na/Pi uptake. These results indicate that PMA-induced stimulation of Na/Pi uptake by Pit-2 is specifically mediated through activation of PKCepsilon. JF - The Journal of biological chemistry AU - Jobbagy, Z AU - Olah, Z AU - Petrovics, G AU - Eiden, M V AU - Leverett, B D AU - Dean, N M AU - Anderson, W B AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892, USA. Y1 - 1999/03/12/ PY - 1999 DA - 1999 Mar 12 SP - 7067 EP - 7071 VL - 274 IS - 11 SN - 0021-9258, 0021-9258 KW - Carrier Proteins KW - 0 KW - Isoenzymes KW - Oligonucleotides, Antisense KW - Phosphates KW - Receptors, Virus KW - Slc20a1 protein, mouse KW - Slc20a2 protein, mouse KW - Sodium-Phosphate Cotransporter Proteins KW - Sodium-Phosphate Cotransporter Proteins, Type III KW - Symporters KW - Prkce protein, mouse KW - EC 2.7.1.- KW - Protein Kinase C KW - EC 2.7.11.13 KW - Protein Kinase C-epsilon KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Phosphates -- metabolism KW - Animals KW - 3T3 Cells KW - Enzyme Activation KW - Biological Transport KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Oligonucleotides, Antisense -- pharmacology KW - Mice KW - Protein Kinase C -- metabolism KW - Retroviridae -- metabolism KW - Carrier Proteins -- metabolism KW - Receptors, Virus -- metabolism KW - Up-Regulation KW - Isoenzymes -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69605165?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Up-regulation+of+the+Pit-2+phosphate+transporter%2Fretrovirus+receptor+by+protein+kinase+C+epsilon.&rft.au=Jobbagy%2C+Z%3BOlah%2C+Z%3BPetrovics%2C+G%3BEiden%2C+M+V%3BLeverett%2C+B+D%3BDean%2C+N+M%3BAnderson%2C+W+B&rft.aulast=Jobbagy&rft.aufirst=Z&rft.date=1999-03-12&rft.volume=274&rft.issue=11&rft.spage=7067&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. AN - 69595496; 10072411 AB - In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P=0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity. JF - The New England journal of medicine AU - Walsh, T J AU - Finberg, R W AU - Arndt, C AU - Hiemenz, J AU - Schwartz, C AU - Bodensteiner, D AU - Pappas, P AU - Seibel, N AU - Greenberg, R N AU - Dummer, S AU - Schuster, M AU - Holcenberg, J S AD - Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/03/11/ PY - 1999 DA - 1999 Mar 11 SP - 764 EP - 771 VL - 340 IS - 10 SN - 0028-4793, 0028-4793 KW - Antifungal Agents KW - 0 KW - Drug Carriers KW - Liposomes KW - Amphotericin B KW - 7XU7A7DROE KW - Abridged Index Medicus KW - Index Medicus KW - Double-Blind Method KW - Infusions, Intravenous KW - Humans KW - Kidney -- drug effects KW - Aged KW - Child KW - Child, Preschool KW - Aged, 80 and over KW - Adult KW - Treatment Outcome KW - Middle Aged KW - Antibiotic Prophylaxis KW - Adolescent KW - Male KW - Female KW - Antifungal Agents -- adverse effects KW - Mycoses -- prevention & control KW - Amphotericin B -- adverse effects KW - Amphotericin B -- administration & dosage KW - Mycoses -- drug therapy KW - Antifungal Agents -- administration & dosage KW - Fever -- drug therapy KW - Neutropenia -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69595496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Liposomal+amphotericin+B+for+empirical+therapy+in+patients+with+persistent+fever+and+neutropenia.+National+Institute+of+Allergy+and+Infectious+Diseases+Mycoses+Study+Group.&rft.au=Walsh%2C+T+J%3BFinberg%2C+R+W%3BArndt%2C+C%3BHiemenz%2C+J%3BSchwartz%2C+C%3BBodensteiner%2C+D%3BPappas%2C+P%3BSeibel%2C+N%3BGreenberg%2C+R+N%3BDummer%2C+S%3BSchuster%2C+M%3BHolcenberg%2C+J+S&rft.aulast=Walsh&rft.aufirst=T&rft.date=1999-03-11&rft.volume=340&rft.issue=10&rft.spage=764&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-11 N1 - Date created - 1999-03-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: N Engl J Med. 2005 Jan 27;352(4):410-4; author reply 410-4 [15675091] N Engl J Med. 2002 May 30;346(22):1745-7; author reply 1745-7 [12041526] N Engl J Med. 1999 Oct 7;341(15):1152-3; author reply 1154-5 [10515751] N Engl J Med. 2004 Sep 30;351(14):1445-7 [15459307] N Engl J Med. 1999 Oct 7;341(15):1154-5 [10515755] N Engl J Med. 1999 Oct 7;341(15):1153-4; author reply 1154-5 [10515754] N Engl J Med. 1999 Oct 7;341(15):1153; author reply 1154-5 [10515753] N Engl J Med. 1999 Oct 7;341(15):1152; author reply 1154-5 [10515750] N Engl J Med. 1999 Oct 7;341(15):1153; author reply 1154-5 [10515752] N Engl J Med. 2002 May 30;346(22):1745-7; author reply 1745-7 [12041527] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Postexposure Chemoprophylaxis for Occupational Exposures to the Human Immunodeficiency Virus AN - 17237035; 4515369 AB - Postexposure chemoprophylaxis is now recommended for health care workers who experience certain kinds of occupational exposures to the human immunodeficiency virus (HIV) in the workplace. Substantial information has emerged that supports but does not prove the efficacy of antiretroviral agents in preventing HIV infection after occupational exposure. This article reviews the data that have accrued in the past 8 years that bear directly on this question and describes a systematic approach to the clinical management of health care workers occupationally exposed to HIV. JF - Journal of the American Medical Association AU - Henderson, D K AD - Bldg 10, Room 2C146, National Institutes of Health, 10 Center Dr, MSC-1504, Bethesda, MD 20892-1504, USA, dkh@nih.gov Y1 - 1999/03/10/ PY - 1999 DA - 1999 Mar 10 SP - 931 EP - 936 VL - 281 IS - 10 SN - 0098-7484, 0098-7484 KW - HIV-1 KW - antiviral agents KW - chemotherapy KW - prophylaxis KW - Health & Safety Science Abstracts; Virology & AIDS Abstracts KW - Chemotherapy KW - Medical personnel KW - Antiviral agents KW - Human immunodeficiency virus KW - Human immunodeficiency virus 1 KW - Occupational exposure KW - H 1000:Occupational Safety and Health KW - V 22004:AIDS: Clinical aspects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17237035?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthsafetyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Medical+Association&rft.atitle=Postexposure+Chemoprophylaxis+for+Occupational+Exposures+to+the+Human+Immunodeficiency+Virus&rft.au=Henderson%2C+D+K&rft.aulast=Henderson&rft.aufirst=D&rft.date=1999-03-10&rft.volume=281&rft.issue=10&rft.spage=931&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Medical+Association&rft.issn=00987484&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Medical personnel; Occupational exposure; Chemotherapy; Human immunodeficiency virus; Antiviral agents ER - TY - JOUR T1 - Genomic organization and regulation by dietary fat of the uncoupling protein 3 and 2 genes. AN - 69606693; 10066417 AB - Uncoupling protein-1 (UCP1) dissipates the transmitochondrial proton gradient as heat. UCP2 and UCP3 are two recently discovered homologues that also have uncoupling activity and thus presumably have a role in energy homeostasis. We now report the genomic structure of murine UCP3 (7 exons) and UCP2 (8 exons). UCP3 is approximately 8 kilobases upstream of UCP2. An UCP3 variant mRNA, UCP3S, was also found and characterized. The effect of a high fat diet (45% versus 10%) on UCP3 and UCP2 mRNA levels was measured. Eating the 45% fat diet for eight weeks caused greater weight gain in AKR and C57BL/6J mice than in the obesity-resistant A/J mice. The high fat diet increased muscle UCP3 expression twofold in C57BL/6J animals. UCP2 expression increased slightly on the 45% fat diet in white adipose of AKR mice, but not in A/J or C57BL/6J mice. In skeletal muscle, UCP2 expression showed little variation with diet. Thus, UCP2 and UCP3 expression levels change in response to diet-induced obesity, but the changes are modest and depend on the tissue and genotype. The data suggest that it is not a reduction in UCP2 or UCP3 expression that causes obesity in the susceptible mice. Copyright 1999 Academic Press. JF - Biochemical and biophysical research communications AU - Gong, D W AU - He, Y AU - Reitman, M L AD - Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, 20892-1770, USA. dwg@helix.nih.gov Y1 - 1999/03/05/ PY - 1999 DA - 1999 Mar 05 SP - 27 EP - 32 VL - 256 IS - 1 SN - 0006-291X, 0006-291X KW - Carrier Proteins KW - 0 KW - Dietary Fats KW - Ion Channels KW - Membrane Transport Proteins KW - Mitochondrial Proteins KW - Protein Isoforms KW - Proteins KW - RNA, Messenger KW - UCP2 protein, human KW - UCP3 protein, human KW - Ucp2 protein, mouse KW - Ucp3 protein, mouse KW - Uncoupling Protein 2 KW - Uncoupling Protein 3 KW - Index Medicus KW - Animals KW - Disease Susceptibility KW - Humans KW - Amino Acid Sequence KW - Mice KW - RNA, Messenger -- genetics KW - Cloning, Molecular KW - Exons -- genetics KW - Polymerase Chain Reaction KW - Mice, Inbred Strains KW - Adipose Tissue -- metabolism KW - RNA, Messenger -- metabolism KW - Obesity -- genetics KW - Alternative Splicing KW - Molecular Sequence Data KW - Sequence Homology, Amino Acid KW - Protein Isoforms -- genetics KW - Obesity -- chemically induced KW - Muscle, Skeletal -- metabolism KW - Carrier Proteins -- genetics KW - Dietary Fats -- administration & dosage KW - Gene Expression Regulation KW - Proteins -- genetics KW - Dietary Fats -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69606693?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Genomic+organization+and+regulation+by+dietary+fat+of+the+uncoupling+protein+3+and+2+genes.&rft.au=Gong%2C+D+W%3BHe%2C+Y%3BReitman%2C+M+L&rft.aulast=Gong&rft.aufirst=D&rft.date=1999-03-05&rft.volume=256&rft.issue=1&rft.spage=27&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF053352; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of amino insertion mutations in the fingers subdomain of HIV-1 reverse transcriptase. AN - 69599489; 10047477 AB - In response to dideoxy inosine/hydroxyurea dual therapy, HIV-1 (human immunodeficiency virus type-1) variants were isolated that had a small amino acid insertion and flanking amino acid substitutions in the fingers subdomain of HIV-1. We have analyzed the reverse transcriptase variants for their effects on HIV-1 reverse transcriptase activity. The data suggests that the inserted amino acid residues are responsible for low-level resistance to the nucleoside analog ddITP, while the role of the flanking amino acid substitutions is to compensate for the deleterious effects of the insertion. Copyright 1999 Academic Press. JF - Journal of molecular biology AU - Boyer, P L AU - Lisziewicz, J AU - Lori, F AU - Hughes, S H AD - ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD, 21702-1201, USA. Y1 - 1999/03/05/ PY - 1999 DA - 1999 Mar 05 SP - 995 EP - 1008 VL - 286 IS - 4 SN - 0022-2836, 0022-2836 KW - Anti-HIV Agents KW - 0 KW - Deoxyadenine Nucleotides KW - Dideoxynucleotides KW - 2',3'-dideoxyadenosine triphosphate KW - 24027-80-3 KW - HIV Reverse Transcriptase KW - EC 2.7.7.49 KW - Didanosine KW - K3GDH6OH08 KW - Index Medicus KW - AIDS/HIV KW - HIV Infections -- virology KW - Kinetics KW - Humans KW - Anti-HIV Agents -- pharmacology KW - Drug Resistance, Microbial -- genetics KW - Mutagenesis, Insertional KW - Didanosine -- pharmacology KW - Deoxyadenine Nucleotides -- pharmacology KW - Protein Conformation KW - HIV Reverse Transcriptase -- genetics KW - HIV-1 -- genetics KW - HIV Reverse Transcriptase -- metabolism KW - HIV-1 -- enzymology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69599489?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Analysis+of+amino+insertion+mutations+in+the+fingers+subdomain+of+HIV-1+reverse+transcriptase.&rft.au=Boyer%2C+P+L%3BLisziewicz%2C+J%3BLori%2C+F%3BHughes%2C+S+H&rft.aulast=Boyer&rft.aufirst=P&rft.date=1999-03-05&rft.volume=286&rft.issue=4&rft.spage=995&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Saturation mutagenesis of the E. coli RecA loop L2 homologous DNA pairing region reveals residues essential for recombination and recombinational repair. AN - 69598685; 10047484 AB - The disordered mobile loop L2 of the Escherichia coli RecA protein is known to play a central role in DNA binding and pairing. To investigate the local chemical environment in relation to function we performed saturation mutagenesis of the loop L2 region (amino acid positions 193-212) using a site-directed mutagenesis procedure, and determined the recombinational proficiency of the 380 mutants using genetic assays for homologous recombination and recombinational repair. Residues Asn193, Gln194, Arg196, Glu207, Thr209, Gly211, and Gly212 were identified as stringently required for recombinational events in bacterial cells. In addition, our findings suggest the involvement of loop L2 in the ATPase activity of RecA, and a role for residues Gln194, Arg196, Lys198 and Thr209 in the DNA-dependent hydrolysis of ATP. Finally, since 20 residue peptides that comprise this region can pair homologous DNAs by forming filamentous beta-structures, we propose how the information from the mutant analysis might facilitate the use of a simplified amino acid alphabet to design beta-structure forming L2 peptides with improved RecA-like activities. Copyright 1999 Academic Press. JF - Journal of molecular biology AU - Hörtnagel, K AU - Voloshin, O N AU - Kinal, H H AU - Ma, N AU - Schaffer-Judge, C AU - Camerini-Otero, R D AD - Genetics and Biochemistry Branch, NIDDK, National Institutes of Health, Bethesda, MD, 20892-1810, USA. Y1 - 1999/03/05/ PY - 1999 DA - 1999 Mar 05 SP - 1097 EP - 1106 VL - 286 IS - 4 SN - 0022-2836, 0022-2836 KW - Rec A Recombinases KW - EC 2.7.7.- KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Nucleic Acid Conformation KW - Protein Conformation KW - Rec A Recombinases -- genetics KW - DNA Repair KW - Recombination, Genetic KW - Rec A Recombinases -- chemistry KW - Escherichia coli -- genetics KW - Rec A Recombinases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69598685?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Saturation+mutagenesis+of+the+E.+coli+RecA+loop+L2+homologous+DNA+pairing+region+reveals+residues+essential+for+recombination+and+recombinational+repair.&rft.au=H%C3%B6rtnagel%2C+K%3BVoloshin%2C+O+N%3BKinal%2C+H+H%3BMa%2C+N%3BSchaffer-Judge%2C+C%3BCamerini-Otero%2C+R+D&rft.aulast=H%C3%B6rtnagel&rft.aufirst=K&rft.date=1999-03-05&rft.volume=286&rft.issue=4&rft.spage=1097&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Synergistic effects of retinoic acid and 8-Cl-cAMP on apoptosis require caspase-3 activation in human ovarian cancer cells. AN - 69704994; 10208436 AB - We investigated the intracellular mechanisms of retinoic acid (9-cis-RA, 13-cis-RA or all-trans-RA) and a cyclic AMP analog 8-Cl-cAMP on growth-inhibition and apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. The cyclic AMP analog, 8-Cl-cAMP, acted synergistically with RA in inducing and activating retinoic acid receptor beta (RARbeta) which correlated with the growth inhibition, cell cycle arrest, and apoptosis in both cell types. In addition, combined treatment of cells with RA plus 8-Cl-cAMP resulted in the release of cytochrome c, loss in mitochondrial membrane potential and activation of caspase-3 followed by cleavage of anti-poly(ADP-ribose)polymerase and DNA-dependent protein kinase (catalytic subunit). Interestingly, inhibition of caspase-3 activation blocked RA plus 8-Cl-cAMP induced apoptosis. Furthermore, mutations in a CRE-related motif within the RARbeta promoter resulted in loss of both transcriptional activation of RARbeta and synergy between RA and 8-Cl-cAMP. Thus, RARbeta can mediate RA and/or cyclic AMP action in ovarian cancer cells by promoting apoptosis. Loss of RARbeta expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. These findings suggest that RA and 8-Cl-cAMP act in a synergistic fashion in inducing apoptosis via caspase-3 activation, and may have potential for combination biotherapy for the treatment of malignant disease such as ovarian cancer. JF - Oncogene AU - Srivastava, R K AU - Srivastava, A R AU - Cho-Chung, Y S AU - Longo, D L AD - Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224-6825, USA. Y1 - 1999/03/04/ PY - 1999 DA - 1999 Mar 04 SP - 1755 EP - 1763 VL - 18 IS - 9 SN - 0950-9232, 0950-9232 KW - Cytochrome c Group KW - 0 KW - DNA-Binding Proteins KW - Nuclear Proteins KW - Receptors, Retinoic Acid KW - retinoic acid receptor beta KW - 8-Bromo Cyclic Adenosine Monophosphate KW - 23583-48-4 KW - 8-chloro-cyclic adenosine monophosphate KW - 41941-56-4 KW - Tretinoin KW - 5688UTC01R KW - Poly(ADP-ribose) Polymerases KW - EC 2.4.2.30 KW - DNA-Activated Protein Kinase KW - EC 2.7.11.1 KW - PRKDC protein, human KW - Protein-Serine-Threonine Kinases KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Index Medicus KW - Receptors, Retinoic Acid -- metabolism KW - Protein-Serine-Threonine Kinases -- metabolism KW - Ovarian Neoplasms KW - Enzyme Activation KW - Humans KW - Amino Acid Sequence KW - Poly(ADP-ribose) Polymerases -- metabolism KW - Tumor Cells, Cultured KW - Cell Survival -- drug effects KW - Molecular Sequence Data KW - Cytochrome c Group -- metabolism KW - Drug Synergism KW - Cell Cycle -- drug effects KW - Female KW - Tretinoin -- pharmacology KW - 8-Bromo Cyclic Adenosine Monophosphate -- analogs & derivatives KW - Apoptosis KW - 8-Bromo Cyclic Adenosine Monophosphate -- metabolism KW - Tretinoin -- metabolism KW - 8-Bromo Cyclic Adenosine Monophosphate -- pharmacology KW - Caspases -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69704994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Synergistic+effects+of+retinoic+acid+and+8-Cl-cAMP+on+apoptosis+require+caspase-3+activation+in+human+ovarian+cancer+cells.&rft.au=Srivastava%2C+R+K%3BSrivastava%2C+A+R%3BCho-Chung%2C+Y+S%3BLongo%2C+D+L&rft.aulast=Srivastava&rft.aufirst=R&rft.date=1999-03-04&rft.volume=18&rft.issue=9&rft.spage=1755&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1. AN - 69697728; 10208427 AB - Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291-2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region. JF - Oncogene AU - Rojas, J M AU - Subleski, M AU - Coque, J J AU - Guerrero, C AU - Saez, R AU - Li, B Q AU - Lopez, E AU - Zarich, N AU - Aroca, P AU - Kamata, T AU - Santos, E AD - Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/03/04/ PY - 1999 DA - 1999 Mar 04 SP - 1651 EP - 1661 VL - 18 IS - 9 SN - 0950-9232, 0950-9232 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - GRB2 Adaptor Protein KW - GRB2 protein, human KW - Grb2 protein, mouse KW - Guanine Nucleotide Exchange Factors KW - Protein Isoforms KW - Proteins KW - ras Guanine Nucleotide Exchange Factors KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Binding Sites KW - Transfection KW - Transformation, Genetic KW - Molecular Sequence Data KW - ras Proteins -- metabolism KW - Mutagenesis, Insertional KW - Proteins -- metabolism KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69697728?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=Isoform-specific+insertion+near+the+Grb2-binding+domain+modulates+the+intrinsic+guanine+nucleotide+exchange+activity+of+hSos1.&rft.au=Rojas%2C+J+M%3BSubleski%2C+M%3BCoque%2C+J+J%3BGuerrero%2C+C%3BSaez%2C+R%3BLi%2C+B+Q%3BLopez%2C+E%3BZarich%2C+N%3BAroca%2C+P%3BKamata%2C+T%3BSantos%2C+E&rft.aulast=Rojas&rft.aufirst=J&rft.date=1999-03-04&rft.volume=18&rft.issue=9&rft.spage=1651&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-01 N1 - Date created - 1999-06-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. AN - 69601707; 10051580 AB - CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Buters, J T AU - Sakai, S AU - Richter, T AU - Pineau, T AU - Alexander, D L AU - Savas, U AU - Doehmer, J AU - Ward, J M AU - Jefcoate, C R AU - Gonzalez, F J AD - National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03/02/ PY - 1999 DA - 1999 Mar 02 SP - 1977 EP - 1982 VL - 96 IS - 5 SN - 0027-8424, 0027-8424 KW - Carcinogens KW - 0 KW - Polychlorinated Dibenzodioxins KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cyp1b1 protein, mouse KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Animals KW - Fibroblasts -- enzymology KW - Polychlorinated Dibenzodioxins -- pharmacology KW - Organ Specificity KW - Mice KW - Genomic Library KW - Mice, Knockout KW - 9,10-Dimethyl-1,2-benzanthracene -- pharmacokinetics KW - Chimera KW - Biotransformation KW - Cells, Cultured KW - Restriction Mapping KW - Lung -- enzymology KW - Stem Cells KW - Embryo, Mammalian KW - Female KW - Neoplasms, Experimental -- chemically induced KW - Lymphoma -- genetics KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Neoplasms, Experimental -- genetics KW - Lymphoma -- chemically induced KW - Genetic Predisposition to Disease UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69601707?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Cytochrome+P450+CYP1B1+determines+susceptibility+to+7%2C+12-dimethylbenz%5Ba%5Danthracene-induced+lymphomas.&rft.au=Buters%2C+J+T%3BSakai%2C+S%3BRichter%2C+T%3BPineau%2C+T%3BAlexander%2C+D+L%3BSavas%2C+U%3BDoehmer%2C+J%3BWard%2C+J+M%3BJefcoate%2C+C+R%3BGonzalez%2C+F+J&rft.aulast=Buters&rft.aufirst=J&rft.date=1999-03-02&rft.volume=96&rft.issue=5&rft.spage=1977&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Hum Mol Genet. 1997;6(10):1667-77 [9300658] Mol Cell Biol. 1986 May;6(5):1471-7 [3785172] J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12 [2359136] Mol Cell Biol. 1995 Jun;15(6):3012-22 [7539101] Pharmacogenetics. 1996 Feb;6(1):1-42 [8845856] Drug Metab Rev. 1997 Nov;29(4):1107-27 [9421687] Nucleic Acids Res. 1991 Aug 11;19(15):4293 [1870982] Endocrinology. 1992 Dec;131(6):3067-76 [1332854] Endocrinology. 1991 Aug;129(2):970-82 [1649753] Mutagenesis. 1997 Mar;12(2):83-9 [9106248] Anal Biochem. 1985 Oct;150(1):76-85 [3843705] Arch Biochem Biophys. 1991 May 1;286(2):488-97 [1910294] Cancer Res. 1973 Dec;33(12):3239-49 [4796800] Drug Metab Dispos. 1997 May;25(5):617-22 [9152602] Mol Pharmacol. 1998 Dec;54(6):1000-6 [9855628] Cell. 1991 Jun 28;65(7):1153-63 [2065352] Carcinogenesis. 1997 Mar;18(3):553-9 [9067556] Chem Biol Interact. 1997 Oct 24;106(3):161-82 [9413544] Biochem Pharmacol. 1993 Sep 1;46(5):787-90 [8373431] Mol Pharmacol. 1989 Jul;36(1):83-8 [2501655] Cancer Res. 1997 Oct 15;57(20):4498-506 [9377560] Endocrinology. 1995 Nov;136(11):5034-41 [7588239] Biotechniques. 1988 Feb;6(2):114-6 [2908499] Hum Mol Genet. 1997 Apr;6(4):641-7 [9097971] Arch Biochem Biophys. 1998 Sep 1;357(1):111-20 [9721189] J Biol Chem. 1995 May 12;270(19):11595-602 [7744798] Science. 1991 Oct 18;254(5030):415-8 [1925598] J Biol Chem. 1994 May 6;269(18):13092-9 [8175734] J Biol Chem. 1996 Nov 8;271(45):28324-30 [8910454] J Biol Chem. 1998 Feb 27;273(9):5174-83 [9478971] J Biol Chem. 1994 May 27;269(21):14905-11 [8195121] Nature. 1988 Nov 24;336(6197):348-52 [3194019] Carcinogenesis. 1990 Feb;11(2):321-7 [2154339] Arch Biochem Biophys. 1997 Nov 15;347(2):181-92 [9367523] Carcinogenesis. 1994 Apr;15(4):725-32 [8149487] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In vivo analysis of the 3' untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone. AN - 69601698; 10051634 AB - Large sections of the 3' untranslated region (UTR) of hepatitis C virus (HCV) were deleted from an infectious cDNA clone, and the RNA transcripts from seven deletion mutants were tested sequentially for infectivity in a chimpanzee. Mutants lacking all or part of the 3' terminal conserved region or the poly(U-UC) region were unable to infect the chimpanzee, indicating that both regions are critical for infectivity in vivo. However, the third region, the variable region, was able to tolerate a deletion that destroyed the two putative stem-loop structures within this region. Mutant VR-24 containing a deletion of the proximal 24 nt of the variable region of the 3' UTR was viable in the chimpanzee and seemed to replicate as well as the undeleted parent virus. The chimpanzee became viremic 1 week after inoculation with mutant VR-24, and the HCV genome titer increased over time during the early acute infection. Therefore, the poly(U-UC) region and the conserved region, but not the variable region, of the 3' UTR seem to be critical for in vivo infectivity of HCV. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Yanagi, M AU - St Claire, M AU - Emerson, S U AU - Purcell, R H AU - Bukh, J AD - Hepatitis Viruses and Molecular Hepatitis Sections, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03/02/ PY - 1999 DA - 1999 Mar 02 SP - 2291 EP - 2295 VL - 96 IS - 5 SN - 0027-8424, 0027-8424 KW - 3' Untranslated Regions KW - 0 KW - DNA, Complementary KW - DNA, Viral KW - Index Medicus KW - Polymerase Chain Reaction KW - Animals KW - Base Sequence KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Sequence Deletion KW - Pan troglodytes KW - Mutagenesis KW - Hepacivirus -- pathogenicity KW - DNA, Viral -- chemistry KW - Hepatitis C -- blood KW - Hepacivirus -- genetics KW - 3' Untranslated Regions -- chemistry KW - Transcription, Genetic KW - 3' Untranslated Regions -- genetics KW - DNA, Viral -- genetics KW - Hepatitis C -- physiopathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69601698?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=In+vivo+analysis+of+the+3%27+untranslated+region+of+the+hepatitis+C+virus+after+in+vitro+mutagenesis+of+an+infectious+cDNA+clone.&rft.au=Yanagi%2C+M%3BSt+Claire%2C+M%3BEmerson%2C+S+U%3BPurcell%2C+R+H%3BBukh%2C+J&rft.aulast=Yanagi&rft.aufirst=M&rft.date=1999-03-02&rft.volume=96&rft.issue=5&rft.spage=2291&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4942-6 [1317578] Nat Med. 1998 Dec;4(12):1438-40 [9846585] J Virol. 1995 Jan;69(1):32-8 [7983724] Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3401-5 [7724574] Biochem Biophys Res Commun. 1995 Oct 13;215(2):744-9 [7488017] EMBO J. 1996 Jan 2;15(1):12-22 [8598194] Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1711-5 [1705704] J Virol. 1996 May;70(5):3307-12 [8627816] J Virol. 1996 Jun;70(6):3363-71 [8648666] J Virol. 1996 Jun;70(6):3930-7 [8648730] J Gen Virol. 1996 Feb;77 ( Pt 2 ):293-301 [8627233] Virology. 1996 Sep 1;223(1):255-61 [8806561] J Infect Dis. 1996 Dec;174(6):1324-7 [8940226] J Virol. 1997 Feb;71(2):1497-505 [8995675] Wkly Epidemiol Rec. 1997 Mar 7;72(10):65-9 [9115857] Science. 1997 Jul 25;277(5325):570-4 [9228008] Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8738-43 [9238047] Am J Pathol. 1997 Aug;151(2):363-73 [9250150] J Virol. 1997 Sep;71(9):6720-6 [9261396] Hepatology. 1997 Sep;26(3 Suppl 1):15S-20S [9305658] J Virol. 1997 Oct;71(10):7345-52 [9311812] J Virol. 1997 Nov;71(11):8416-28 [9343198] J Virol. 1997 Nov;71(11):8698-706 [9343228] J Virol. 1998 Mar;72(3):2132-40 [9499069] Biochem Biophys Res Commun. 1998 Apr 7;245(1):198-203 [9535808] Virology. 1998 Apr 25;244(1):161-72 [9581788] J Virol. 1998 Sep;72(9):7510-22 [9696848] J Gen Virol. 1998 Aug;79 ( Pt 8):1847-57 [9714232] Clin Diagn Virol. 1998 Jul 15;10(2-3):173-9 [9741643] J Virol. 1998 Nov;72(11):8789-96 [9765423] J Infect Dis. 1998 Oct;178(4):1193-7 [9806059] Nucleic Acids Res. 1992 Jul 11;20(13):3520 [1321416] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Interferon gamma expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity AN - 17167133; 4462483 AB - Interferon gamma (IFN- gamma ) has pleiotropic biological effects including intrinsic antiviral activity as well as stimulation and regulation of immune responses. An infectious recombinant human respiratory syncytial virus (rRSV/mIFN- gamma ) was constructed that encodes murine (m) IFN- gamma as a separate gene inserted into the G-F intergenic region. Cultured cells infected with rRSV/mIFN- gamma secreted 22 mu g mIFN- gamma per 10 super(6) cells. The replication of rRSV/mIFN- gamma , but not that of a control chimeric rRSV containing the chloramphenicol acetyl transferase (CAT) gene as an additional gene was 63- and 20-fold lower than that of wild-type (wt) RSV in the upper and lower respiratory tract, respectively, of mice. Thus, the attenuation of rRSV/mIFN- gamma in vivo could be attributed to the activity of mIFN- gamma and not to the presence of the additional gene per se. The mice were completely resistant to subsequent challenge with wt RSV. Despite its growth restriction, infection of mice with rRSV/mIFN- gamma induced a level of RSV-specific antibodies that, on day 56, was comparable to or greater than that induced by infection with wt RSV. Mice infected with rRSV/mIFN- gamma developed a high level of IFN- gamma mRNA and an increased amount of interleukin 12 p40 mRNA in their lungs, whereas other cytokine mRNAs tested were unchanged compared with those induced by wt RSV. Because attenuation of RSV typically is accompanied by a reduction in immunogenicity, expression of IFN- gamma by an rRSV represents a method of attenuation in which immunogenicity can be maintained rather than be reduced. JF - Proceedings of the National Academy of Sciences, USA AU - Bukreyev, A AU - Whitehead, S S AU - Bukreyeva, N AU - Murphy, B R AU - Collins, P L AD - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Building 7, Room 100, 7 Center Drive, Bethesda, MD 20892-0720 USA, pcollins@atlas.niaid.nih.gov Y1 - 1999/03/02/ PY - 1999 DA - 1999 Mar 02 SP - 2367 EP - 2372 VL - 96 IS - 05 SN - 0027-8424, 0027-8424 KW - gamma -Interferon KW - mice KW - respiratory syncytial virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Biochemistry Abstracts 2: Nucleic Acids KW - Interleukin 12 KW - Chloramphenicol O-acetyltransferase KW - Respiratory tract KW - Replication KW - Respiratory syncytial virus KW - F 06773:Interferons KW - V 22050:Viral genetics including virus reactivation KW - W3 33330:Cytokines KW - W 30965:Miscellaneous, Reviews KW - N 14551:Virus & phage infections KW - F 06800:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17167133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Interferon+gamma+expressed+by+a+recombinant+respiratory+syncytial+virus+attenuates+virus+replication+in+mice+without+compromising+immunogenicity&rft.au=Bukreyev%2C+A%3BWhitehead%2C+S+S%3BBukreyeva%2C+N%3BMurphy%2C+B+R%3BCollins%2C+P+L&rft.aulast=Bukreyev&rft.aufirst=A&rft.date=1999-03-02&rft.volume=96&rft.issue=05&rft.spage=2367&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Respiratory syncytial virus; respiratory syncytial virus; Replication; Respiratory tract; Interleukin 12; Chloramphenicol O-acetyltransferase ER - TY - JOUR T1 - Yeast and human genes that affect the Escherichia coli SOS response AN - 17163154; 4462454 AB - The sequencing of the human genome has led to the identification of many genes whose functions remain to be determined. Because of conservation of genetic function, microbial systems have often been used for identification and characterization of human genes. We have investigated the use of the Escherichia coli SOS induction assay as a screen for yeast and human genes that might play a role in DNA metabolism and/or in genome stability. The SOS system has previously been used to analyze bacterial and viral genes that directly modify DNA. An initial screen of meiotically expressed yeast genes revealed several genes associated with chromosome metabolism (e.g. RAD51 and HHT1 as well as others). The SOS induction assay was then extended to the isolation of human genes. Several known human genes involved in DNA metabolism, such as the Ku70 end-binding protein and DNA ligase IV, were identified, as well as a large number of previously unknown genes. Thus, the SOS assay can be used to identify and characterize human genes, many of which may participate in chromosome metabolism. JF - Proceedings of the National Academy of Sciences, USA AU - Perkins, EL AU - Sterling, J F AU - Hashem, VI AU - Resnick, MA AD - Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, 111 TW Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, resnick@niehs.nih.gov Y1 - 1999/03/02/ PY - 1999 DA - 1999 Mar 02 SP - 2204 EP - 2209 VL - 96 IS - 05 SN - 0027-8424, 0027-8424 KW - DNA ligase IV KW - HHT1 gene KW - Ku70 end-binding protein KW - RAD51 gene KW - Rad51 gene KW - SOS response KW - budding yeast KW - man KW - Microbiology Abstracts B: Bacteriology; Genetics Abstracts; Microbiology Abstracts C: Algology, Mycology & Protozoology KW - Chromosomes KW - Escherichia coli KW - Saccharomyces cerevisiae KW - K 03079:Fungi KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17163154?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.atitle=Yeast+and+human+genes+that+affect+the+Escherichia+coli+SOS+response&rft.au=Perkins%2C+EL%3BSterling%2C+J+F%3BHashem%2C+VI%3BResnick%2C+MA&rft.aulast=Perkins&rft.aufirst=EL&rft.date=1999-03-02&rft.volume=96&rft.issue=05&rft.spage=2204&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences%2C+USA&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; Saccharomyces cerevisiae; Chromosomes ER - TY - JOUR T1 - International Variation in the Incidence of Hip Fractures: Cross-National Project on Osteoporosis for the World Health Organization Program for Research on Aging AN - 954612042; 14325824 AB - A cross-national study of hip fracture incidence was carried out in five geographic areas - Beijing, China; Budapest, Hungary; Hong Kong; Porto Alegre, Brazil; and Reykjavik, Iceland - during the years 1990-1992. Cases of hip fracture among women and men of age 20 years and older were identified using hospital discharge data in conjunction with medical records, operating room logs, and radiology logs. Estimated incidence rates varied widely, with Beijing reporting the lowest rates (age-adjusted rate per 100000 population for men 20 years and older = 45.4; women = 39.6) and Reykjavik the highest rates (men = 141.3; women = 274.1). Rates were higher for women than for men in every area except Beijing. In every area except Budapest, review of the operating room or radiology logs identified additional cases that were not reported in the discharge list, increasing the estimated number of hip fractures by 11% to 62%, depending on the area. Review of medical records identified miscoding of hip fractures (ICD9 820) as 'shaft of femur and other femur fractures' (ICD9 821) in the discharge lists of every area except Budapest, increasing the estimated number of hip fractures by 1% to 30%. The final estimates of hip fracture incidence taking into account all investigated sources of undercount and overcount ranged from 15% lower to 89% higher than an estimate based on the discharge diagnoses alone. Although these results indicate substantial limitations in relying on hospital discharge data alone to estimate hip fracture incidence rates, the extent of errors found in the discharge lists is smaller than the large international variation found here and previously reported in incidence rates. The findings support the conclusion that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates. JF - Osteoporosis International AU - Schwartz, A V AU - Kelsey, J L AU - Maggi, S AU - Tuttleman, M AU - Ho, S C AU - Jonsson, P V AU - Poor, G AU - Sisson de Castro, JA AU - Xu, L AU - Matkin, C C AU - Nelson, L M AU - Heyse, S P AD - Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA (formerly at the Office of Prevention, Epidemiology, and Clinical Applications, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH), US Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 242 EP - 253 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 9 IS - 3 SN - 0937-941X, 0937-941X KW - Physical Education Index; Calcium & Calcified Tissue Abstracts KW - Data processing KW - medical records KW - Men KW - Aging KW - Women KW - Fractures KW - Gerontology KW - Osteoporosis KW - Health (programs) KW - Radiology KW - Femur KW - Hips KW - Health (organization) KW - Degenerative diseases KW - Hip KW - Hospitals KW - T 2025:Bone and Bone Diseases KW - PE 030:Exercise, Health & Physical Fitness UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/954612042?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aphysicaleducation&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Osteoporosis+International&rft.atitle=International+Variation+in+the+Incidence+of+Hip+Fractures%3A+Cross-National+Project+on+Osteoporosis+for+the+World+Health+Organization+Program+for+Research+on+Aging&rft.au=Schwartz%2C+A+V%3BKelsey%2C+J+L%3BMaggi%2C+S%3BTuttleman%2C+M%3BHo%2C+S+C%3BJonsson%2C+P+V%3BPoor%2C+G%3BSisson+de+Castro%2C+JA%3BXu%2C+L%3BMatkin%2C+C+C%3BNelson%2C+L+M%3BHeyse%2C+S+P&rft.aulast=Schwartz&rft.aufirst=A&rft.date=1999-03-01&rft.volume=9&rft.issue=3&rft.spage=242&rft.isbn=&rft.btitle=&rft.title=Osteoporosis+International&rft.issn=0937941X&rft_id=info:doi/10.1007%2Fs001980050144 LA - English DB - Physical Education Index N1 - Date revised - 2012-03-01 N1 - Last updated - 2012-03-30 N1 - SubjectsTermNotLitGenreText - Health (organization); Men; Women; Gerontology; Fractures; Health (programs); Degenerative diseases; Hips; Hospitals; Data processing; medical records; Aging; Osteoporosis; Radiology; Femur; Hip DO - http://dx.doi.org/10.1007/s001980050144 ER - TY - JOUR T1 - Activation of toxin ADP-ribosyltransferases by eukaryotic ADP-ribosylation factors AN - 885050079; 13861079 AB - ADP-ribosylation factors (ARFs) are members of a multigene family of 20-kDa guanine nucleotide-binding proteins that ate regulatory components in several pathways of intracellular vesicular trafficking. The relatively small (~180-amino acids) ARF proteins interact with a variety of molecules (in addition to GTP/GDP, of course). Cholera toxin was the first to be recognized, hence the name. Later it was shown that ARF also activates phospholipase D. Different parts of the molecule are responsible for activation of the two enzymes. In vesicular trafficking, ARF must interact with coatomer to recruit it to a membrane and thereby initiate vesicle budding. ARF function requires that it alternate between GTP- and GDP-bound forms, which involves interaction with regulatory proteins. Inactivation of ARF-GTP depends on a GTPase-activating protein or GAP. A guanine nucleotide-exchange protein or GEP accelerates release of bound GDP from inactive ARF-GDP to permit GTP binding. Inhibition of GEP by brefeldin A (BFA) blocks ARF activation and thereby vesicular transport. In cells, it causes apparent disintegration of Golgi structure. Both BFA-sensitive and insensitive GEPs are known. Sequences of peptides from a BFA-sensitive GEP purified in our laboratory revealed the presence of a Sec7 domain, a sequence of ~200 amino acids that resembles a region in the yeast Sec7 gene product, which is involved in Golgi vesicular transport. Other proteins of unknown function also contain Sec7 domains, among them a lymphocyte protein called cytohesin-1. To determine whether it had GEP activity, recombinant cytohesin-1 was synthesized in E. coli. It preferentially activated class I ARFs 1 and 3 and was not inhibited by BFA but failed to activate ARF5 (class II). There are now five Sec7 domain proteins known to have GEP activity toward class I ARFs. It remains to be determined whether there are other Sec7 domain proteins that are GEPs for ARFs 4, 5, or 6. JF - Molecular and Cellular Biochemistry AU - Moss, Joel AU - Vaughan, Martha AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 153 EP - 157 PB - Springer-Verlag, Tiergartenstrasse 17 Heidelberg 69121 Germany VL - 193 IS - 1-2 SN - 0300-8177, 0300-8177 KW - Toxicology Abstracts KW - ADP-ribosylation factor KW - GTPase-activating protein KW - Golgi apparatus KW - NAD(P) super(+)-arginine ADP-ribosyltransferase KW - Phospholipase D KW - Guanine nucleotide-binding protein KW - Enzymes KW - GTP KW - Lymphocytes KW - guanine nucleotide exchange factor KW - regulatory proteins KW - GDP KW - ARF protein KW - Cholera toxin KW - Escherichia coli KW - Brefeldin A KW - Vesicles KW - Budding KW - Amino acid sequence KW - X 24370:Natural Toxins UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/885050079?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+Cellular+Biochemistry&rft.atitle=Activation+of+toxin+ADP-ribosyltransferases+by+eukaryotic+ADP-ribosylation+factors&rft.au=Moss%2C+Joel%3BVaughan%2C+Martha&rft.aulast=Moss&rft.aufirst=Joel&rft.date=1999-03-01&rft.volume=193&rft.issue=1-2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Molecular+and+Cellular+Biochemistry&rft.issn=03008177&rft_id=info:doi/10.1023%2FA%3A1006993000870 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2011-08-01 N1 - Last updated - 2016-03-30 N1 - SubjectsTermNotLitGenreText - GTPase-activating protein; ADP-ribosylation factor; Golgi apparatus; NAD(P) super(+)-arginine ADP-ribosyltransferase; Phospholipase D; GTP; Enzymes; Guanine nucleotide-binding protein; Lymphocytes; guanine nucleotide exchange factor; GDP; regulatory proteins; Cholera toxin; ARF protein; Vesicles; Brefeldin A; Amino acid sequence; Budding; Escherichia coli DO - http://dx.doi.org/10.1023/A:1006993000870 ER - TY - JOUR T1 - Measuring Outcomes "For the Better" AN - 85336300; llba-9913113 AB - In reaction to Anne Hesketh & Karen Sage's (1999) article on speech & language therapy outcomes measurement, areas of agreement & disagreement are outlined. Areas for which agreement is expressed include Hesketh & Sage's definition of the term "outcome," their belief that outcomes are measured at different levels, & their view that impairment-based measurement is a global trend. It is argued that the notion that motivation for outcomes data collection comes from external pressures, eg, service purchasers & administrators, is not accurate. In addition, it is argued that outcomes measurement should address not only the effects, but also the process of a particular intervention in evaluating the effectiveness of that intervention. 6 References. C. Brennan JF - Advances in Speech-Language Pathology AU - Frattali, Carol M AD - W. G. Magnuson Clinical Centre National Instits Health, 10 Centre Dr Room 6S 235 Bethesda MD 20892 carol_frattali@nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 47 EP - 49 VL - 1 IS - 1 SN - 1441-7049, 1441-7049 KW - *Language Therapy (44400) KW - *Speech Therapy (83200) KW - *Measures (Instruments) (52300) KW - article KW - 6812: special education; language therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85336300?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Advances+in+Speech-Language+Pathology&rft.atitle=Measuring+Outcomes+%22For+the+Better%22&rft.au=Frattali%2C+Carol+M&rft.aulast=Frattali&rft.aufirst=Carol&rft.date=1999-03-01&rft.volume=1&rft.issue=1&rft.spage=47&rft.isbn=&rft.btitle=&rft.title=Advances+in+Speech-Language+Pathology&rft.issn=14417049&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2003-10-01 N1 - Last updated - 2014-06-17 N1 - SubjectsTermNotLitGenreText - *Speech Therapy (83200); *Language Therapy (44400); *Measures (Instruments) (52300) ER - TY - JOUR T1 - Effect of muscle activity immediately after botulinum toxin injection for writer's cramp. AN - 85310800; pmid-10091625 AB - Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections. JF - Movement disorders : official journal of the Movement Disorder Society AU - Chen, R AU - Karp, B I AU - Goldstein, S R AU - Bara-Jimenez, W AU - Yaseen, Z AU - Hallett, M AD - Human Motor Control Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892-1428, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 307 EP - 312 VL - 14 IS - 2 SN - 0885-3185, 0885-3185 KW - Index Medicus KW - National Library of Medicine KW - Severity of Illness Index KW - Analysis of Variance KW - Humans KW - Volition -- physiology KW - Motor Activity -- physiology KW - Rest -- physiology KW - Single-Blind Method KW - Muscle Weakness -- chemically induced KW - Adult KW - Cross-Over Studies KW - Motor Activity -- drug effects KW - Middle Aged KW - Male KW - Female KW - Handwriting KW - Botulinum Toxin Type A -- pharmacology KW - Occupational Diseases -- drug therapy KW - Exercise -- physiology KW - Muscle Cramp -- drug therapy KW - Neuromuscular Agents -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85310800?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.atitle=Effect+of+muscle+activity+immediately+after+botulinum+toxin+injection+for+writer%27s+cramp.&rft.au=Chen%2C+R%3BKarp%2C+B+I%3BGoldstein%2C+S+R%3BBara-Jimenez%2C+W%3BYaseen%2C+Z%3BHallett%2C+M&rft.aulast=Chen&rft.aufirst=R&rft.date=1999-03-01&rft.volume=14&rft.issue=2&rft.spage=307&rft.isbn=&rft.btitle=&rft.title=Movement+disorders+%3A+official+journal+of+the+Movement+Disorder+Society&rft.issn=08853185&rft_id=info:doi/ LA - English DB - ComDisDome N1 - Date revised - 2009-01-15 N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - SNARE complex at the ribbon synapses of cochlear hair cells: analysis of synaptic vesicle- and synaptic membrane-associated proteins. AN - 85273611; pmid-10103074 AB - Neurotransmitters are released via exocytosis of synaptic vesicles involving a fusion complex consisting of a set of highly conserved proteins, which form a multiprotein complex resulting in the docking of synaptic vesicles at the site of release. There are three major differences between cochlear hair cell synapses and CNS synapses: (i) hair cells have a specialized structure, the synaptic ribbon, to which synaptic vesicles are attached; (ii) hair cells can maintain high and sustained release of neurotransmitter; and (iii) hair cells lack synaptophysin and synapsin. These differences suggest that an unconventional mechanism of neurotransmitter release may be involved at ribbon synapses. In this study we used different and complementary approaches to determine whether or not ribbon-containing hair cells of the cochlea express any component of the core fusion complex found in conventional synapses. Syntaxin 1, the synaptic membrane synaptosome-associated protein (SNAP)-25 and vesicle-associated membrane protein (VAMP or synaptobrevin) were found to be present in the organ of Corti of both rat and guinea-pig, as shown by reverse transcription polymerase chain reaction and Western blotting. In situ hybridization and immunocytochemistry showed mRNA and protein expression, respectively, in both inner and outer hair cells. Synaptotagmins I and II, generally considered to play major roles in neurotransmitter release at central synapses, were not detected in the organ of Corti. JF - The European Journal of Neuroscience AU - Safieddine, S AU - Wenthold, R J AD - Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. PY - 1999 SP - 803 EP - 812 VL - 11 IS - 3 SN - 0953-816X, 0953-816X KW - Hair Cells KW - Membrane Glycoproteins KW - Guinea Pigs KW - Animal KW - Gene Expression KW - Reverse Transcriptase Polymerase Chain Reaction KW - Membrane Proteins KW - Nerve Tissue Proteins KW - Rats KW - Photoreceptors, Vertebrate KW - RNA, Messenger KW - In Situ Hybridization KW - Blotting, Western KW - Neurotransmitters KW - Synaptic Vesicles KW - Fluorescent Antibody Technique UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85273611?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+European+Journal+of+Neuroscience&rft.atitle=SNARE+complex+at+the+ribbon+synapses+of+cochlear+hair+cells%3A+analysis+of+synaptic+vesicle-+and+synaptic+membrane-associated+proteins.&rft.au=Safieddine%2C+S%3BWenthold%2C+R+J&rft.aulast=Safieddine&rft.aufirst=S&rft.date=1999-03-01&rft.volume=11&rft.issue=3&rft.spage=803&rft.isbn=&rft.btitle=&rft.title=The+European+Journal+of+Neuroscience&rft.issn=0953816X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo. AN - 85264444; pmid-10051233 AB - A growing body of evidence suggests that serotonin plays an important role in the early development of both neural and non-neural tissues from vertebrate and invertebrate species. Serotonin is removed from the extracellular space by the cocaine- and antidepressant-sensitive serotonin transporter, thereby limiting its action on receptors. In situ hybridization histochemistry was used to delineate serotonin transporter messenger RNA expression during rat embryonic development. Serotonin transporter messenger RNA was widely expressed beginning prior to organogenesis and throughout the second half of gestation. Strikingly, serotonin transporter messenger RNA was detected in neural crest cells, some of which respond to serotonin in vitro, and neural crest-derived tissues, such as autonomic ganglia, tooth primordia, adrenal medulla, chondrocytes and neuroepithelial cells, in the skin, heart, intestine and lung. Within the peripheral sensory pathways, two major cells types were serotonin transporter messenger RNA-positive: (i) sensory ganglionic neurons and (ii) neuroepithelial cells which serve as targets for the outgrowing sensory neurons. Several sensory organs (cochlear and retinal ganglionic cells, taste buds, whisker and hair follicles) contained serotonin transporter messenger RNA by late gestation. The expression of serotonin transporter messenger RNA throughout the sensory pathways from central nervous system relay stations [Hansson S. R. et al. (1997) Neuroscience 83, 1185-1201; Lebrand C. et al. (1996) Neuron 17, 823-835] to sensory nerves and target organs as shown in this study suggests that serotonin may regulate peripheral synaptogenesis, and thereby influence later processing of sensory stimuli. If the early detection of serotonin transporter messenger RNA in skin and gastrointestinal and airway epithelia correlates with protein activity, it may permit establishment of a serotonin concentration gradient across epithelia, either from serotonin in the amniotic fluid or from neuronal enteric serotonin, as a developmental cue. Our results demonstrating serotonin transporter messenger RNA in the craniofacial and cardiac areas identify this gene product as the transporter most likely responsible for the previously identified accumulation of serotonin in skin and tooth germ [Lauder J. M. and Zimmerman E. F. (1988) J. craniofac. Genet. devl Biol. 8, 265-276], and the fluoxetine-sensitive effects on craniofacial [Lauder J. M. et al. (1988) Development 102, 709-720; Shuey D. L. et al. (1992) Teratology 46, 367-378; Shuey D. L. et al. (1993) Anat. Embryol., Berlin 187, 75-85] and cardiac [Kirby M. L. and Waldo K. L. (1995) Circulation Res. 77, 211-215; Yavarone M. S. et al. (1993) Teratology 47, 573-584] malformations. Serotonin transporter messenger RNA was detected in several neural crest cell lineages and may be useful as an early marker for the sensory lineage in particular. The distribution of serotonin transporter messenger RNA in early development supports the hypothesis that serotonin may play a role in neural crest cell migration and differentiation [Lauder J. M. (1993) Trends Neurosci. 16, 233-240], and that the morphogenetic actions of serotonin may be regulated by transport. The striking pattern of serotonin transporter messenger RNA throughout developing sensory pathways suggests that serotonin may play a role in establishing patterns of connectivity critical to processing sensory stimuli. As a target for drugs, such as cocaine, amphetamine derivatives and antidepressants, expression of serotonin transporter during development may reflect critical periods of vulnerability for fetal drug exposure. The widespread distribution of serotonin transporter messenger RNA during ontogeny suggests a previously unappreciated role of serotonin in diverse physiological systems during embryonic development. JF - Neuroscience AU - Hansson, S R AU - Mezey, E AU - Hoffman, B J AD - Unit on Molecular Pharmacology, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892-4090, USA. PY - 1999 SP - 243 EP - 265 VL - 89 IS - 1 SN - 0306-4522, 0306-4522 KW - Cochlea KW - Fetus KW - Skin KW - Retina KW - Carrier Proteins KW - Membrane Glycoproteins KW - Neural Crest KW - Animal KW - Brain KW - Gene Expression KW - Tooth KW - Neurons, Afferent KW - Thyroid Gland KW - Pregnancy KW - Facial Bones KW - RNA, Messenger KW - Rats KW - DNA, Complementary KW - In Situ Hybridization KW - Rats, Sprague-Dawley KW - Peripheral Nervous System KW - Tongue KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85264444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience&rft.atitle=Serotonin+transporter+messenger+RNA+expression+in+neural+crest-derived+structures+and+sensory+pathways+of+the+developing+rat+embryo.&rft.au=Hansson%2C+S+R%3BMezey%2C+E%3BHoffman%2C+B+J&rft.aulast=Hansson&rft.aufirst=S&rft.date=1999-03-01&rft.volume=89&rft.issue=1&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Neuroscience&rft.issn=03064522&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - A PET study of human auditory spatial processing. AN - 85262561; pmid-10218879 AB - To learn more about human auditory spatial processing, we used positron emission tomography (PET) to measure regional cerebral blood flow in human volunteers engaged in sound localization tasks. Spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During localization tasks, subjects activated inferior parietal lobules (IPL) bilaterally. In a second experiment, matched in design to the first, subjects made non-spatial auditory discriminations based on frequency, activating the IPL bilaterally with left hemispheric predominance. A between-study comparison revealed that the right IPL was significantly more activated during the sound localization task compared with the feature discrimination task, suggesting a preferential role for the right IPL in auditory spatial processing. JF - Neuroscience Letters AU - Weeks, R A AU - Aziz-Sultan, A AU - Bushara, K O AU - Tian, B AU - Wessinger, C M AU - Dang, N AU - Rauschecker, J P AU - Hallett, M AD - Human Motor Control Section, Medical Neurology Branch, NINDS, NIH, Bethesda, MD 20892-1428, USA. PY - 1999 SP - 155 EP - 158 VL - 262 IS - 3 SN - 0304-3940, 0304-3940 KW - Sound Localization KW - Electrooculography KW - Discrimination (Psychology) KW - Human KW - Adult KW - Brain KW - Tomography, Emission-Computed KW - Psychomotor Performance KW - Parietal Lobe KW - Brain Mapping KW - Cerebrovascular Circulation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85262561?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Neuroscience+Letters&rft.atitle=A+PET+study+of+human+auditory+spatial+processing.&rft.au=Weeks%2C+R+A%3BAziz-Sultan%2C+A%3BBushara%2C+K+O%3BTian%2C+B%3BWessinger%2C+C+M%3BDang%2C+N%3BRauschecker%2C+J+P%3BHallett%2C+M&rft.aulast=Weeks&rft.aufirst=R&rft.date=1999-03-01&rft.volume=262&rft.issue=3&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Neuroscience+Letters&rft.issn=03043940&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - On the role of subthreshold dynamics in neuronal signaling. AN - 85259725; pmid-10074394 AB - The role of subthreshold dynamics in neuronal signaling is examined using periodic pulse train stimulation of the Fitzhugh-Nagumo (FN) model of nerve membrane excitability and results from the squid giant axon as an experimental data base. For a broad range of stimulus conditions the first pulse in a pulse train elicited an action potential, whereas all subsequent pulses elicited subthreshold responses, both in the axon and in the FN model. These results are not well described by the Hodgkin and Huxley 1952 model. Various different patterns of subthreshold responses, including chaotic dynamics, can be observed in both systems-the FN model and the axon-depending upon stimulus conditions. For some conditions action potentials are occasionally interspersed among the subthreshold events with randomly occurring interspike intervals. The randomness is directly attributable to the underlying subthreshold chaos-deterministic chaos-rather than to a stochastic noise source. We conclude that this mechanism may contribute to multimodal interspike interval histograms which have been observed from individual neurons throughout the nervous system. JF - Journal of Theoretical Biology AU - Clay, J R AU - Shrier, A AD - Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. PY - 1999 SP - 207 EP - 216 VL - 197 IS - 2 SN - 0022-5193, 0022-5193 KW - Neurons KW - Animal KW - Support, Non-U.S. Gov't KW - Axons KW - Squid KW - Electric Stimulation KW - Synaptic Transmission KW - Nonlinear Dynamics KW - Action Potentials KW - Models, Neurological UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85259725?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Theoretical+Biology&rft.atitle=On+the+role+of+subthreshold+dynamics+in+neuronal+signaling.&rft.au=Clay%2C+J+R%3BShrier%2C+A&rft.aulast=Clay&rft.aufirst=J&rft.date=1999-03-01&rft.volume=197&rft.issue=2&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Journal+of+Theoretical+Biology&rft.issn=00225193&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study. AN - 85246934; pmid-10080567 AB - OBJECTIVE: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest. JF - The American Journal of Psychiatry AU - Pietrini, P AU - Furey, M L AU - Alexander, G E AU - Mentis, M J AU - Dani, A AU - Guazzelli, M AU - Rapoport, S I AU - Schapiro, M B AD - Laboratory of Neurosciences, National Institute on Aging, NIH, Bethesda, MD 20892, USA. PY - 1999 SP - 470 EP - 473 VL - 156 IS - 3 SN - 0002-953X, 0002-953X KW - Visual Cortex KW - Severity of Illness Index KW - Auditory Cortex KW - Support, U.S. Gov't, P.H.S. KW - Human KW - Alzheimer Disease KW - Brain KW - Glucose KW - Aged KW - Parietal Lobe KW - Photic Stimulation KW - Psychiatric Status Rating Scales KW - Fludeoxyglucose F 18 KW - Support, Non-U.S. Gov't KW - Tomography, Emission-Computed KW - Acoustic Stimulation KW - Male KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85246934?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+Journal+of+Psychiatry&rft.atitle=Association+between+brain+functional+failure+and+dementia+severity+in+Alzheimer%27s+disease%3A+resting+versus+stimulation+PET+study.&rft.au=Pietrini%2C+P%3BFurey%2C+M+L%3BAlexander%2C+G+E%3BMentis%2C+M+J%3BDani%2C+A%3BGuazzelli%2C+M%3BRapoport%2C+S+I%3BSchapiro%2C+M+B&rft.aulast=Pietrini&rft.aufirst=P&rft.date=1999-03-01&rft.volume=156&rft.issue=3&rft.spage=470&rft.isbn=&rft.btitle=&rft.title=The+American+Journal+of+Psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Play in two societies: pervasiveness of process, specificity of structure. AN - 85234235; pmid-10218257 AB - The present study compared Argentine (N = 39) and U.S. (N = 43) children and their mothers on exploratory, symbolic, and social play and interaction when children were 20 months of age. Patterns of cultural similarity and difference emerged. In both cultures, boys engaged in more exploratory play than girls, and girls engaged in more symbolic play than boys; mothers of boys engaged in more exploratory play than mothers of girls, and mothers of girls engaged in more symbolic play than mothers of boys. Moreover, in both cultures, individual variation in children's exploratory and symbolic play was specifically associated with individual variation in mothers' exploratory and symbolic play, respectively. Between cultures, U.S. children and their mothers engaged in more exploratory play, whereas Argentine children and their mothers engaged in more symbolic play. Moreover, Argentine mothers exceeded U.S. mothers in social play and verbal praise of their children. During an early period of mental and social growth, general developmental processes in play may be pervasive, but dyadic and cultural structures are apparently specific. Overall, Argentine and U.S. dyads utilized different modes of exploration, representation, and interaction--emphasizing "other-directed" acts of pretense versus "functional" and "combinatorial" exploration, for example--and these individual and dyadic allocentric versus idiocentric stresses accord with larger cultural concerns of collectivism versus individualism in the two societies. JF - Child Development AU - Bornstein, M H AU - Haynes, O M AU - Pascual, L AU - Painter, K M AU - Galperín C AD - Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-2030, USA. PY - 1999 SP - 317 EP - 331 VL - 70 IS - 2 SN - 0009-3920, 0009-3920 KW - United States KW - Maternal Behavior KW - Analysis of Variance KW - Cooperative Behavior KW - Sex Factors KW - Mother-Child Relations KW - Chi-Square Distribution KW - Human KW - Exploratory Behavior KW - Socialization KW - Infant KW - Fantasy KW - Argentina KW - Child Rearing KW - Infant Behavior KW - Adult KW - Child Development KW - Family Health KW - Play and Playthings KW - Female KW - Male KW - Symbolism KW - Cross-Cultural Comparison KW - Social Behavior UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85234235?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Child+Development&rft.atitle=Play+in+two+societies%3A+pervasiveness+of+process%2C+specificity+of+structure.&rft.au=Bornstein%2C+M+H%3BHaynes%2C+O+M%3BPascual%2C+L%3BPainter%2C+K+M%3BGalper%C3%ADn+C&rft.aulast=Bornstein&rft.aufirst=M&rft.date=1999-03-01&rft.volume=70&rft.issue=2&rft.spage=317&rft.isbn=&rft.btitle=&rft.title=Child+Development&rft.issn=00093920&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Cancer gene therapy update AN - 744716529; 13005967 AB - To provide an update about gene marking and gene therapy trials in cancer patients.Data Sources. A MEDLINE search using the term 'gene therapy' was conducted for the period 1985 to 1998. The reference lists from retrieved articles were reviewed. Meeting abstracts from the American Society of Clinical Oncology annual meeting (published in their proceedings) and the Annual Cancer Gene Therapy Symposium (published in Cancer Gene Therapy) that concerned gene therapy in cancer patients were also included.Data Extraction. Both authors reviewed the retrieved material and included preclinical data, case reports, and clinical trials related to gene transfer or gene therapy in cancer patients.Data Synthesis. There are several possible approaches to using gene therapy for the diagnosis and treatment of cancer and for the monitoring of cancer therapy. Exogenous genes may be used to mark cells to help better understand cancer biology or may be used directly for cancer treatment. Gene-marking trials have already provided new information about cancer biology and have demonstrated that reinfused progenitor cells may be a source of relapse in patients with acute or chronic myelogenous leukemia and neuroblastoma.Approaches using gene therapy for cancer treatment include: using lymphocytes as gene carriers, using foreign genes to increase tumor immunogenicity, introducing tumor regression antigen genes into viruses, introducing 'sensitivity' genes to produce new cytotoxic agent(s) within tumors, producing new protein product(s) to protect normal cells, replacing missing or mutant tumor suppressor genes, and inactivating oncogenes. Clinical trials using these strategies have demonstrated that gene transfer is feasible (albeit with low transduction efficiency) and that gene expression occurs; in addition, clinical responses have been noted. JF - Journal of Oncology Pharmacy Practice AU - Smith, Judith A AU - Goldspiel, Barry R AD - National Institutes of Health Clinical Center Pharmacy Department, Bethesda, Maryland Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 7 EP - 21 PB - Sage Publications Ltd., 6 Bonhill St. London EC2A 4PU UK VL - 5 IS - 1 SN - 1078-1552, 1078-1552 KW - Virology & AIDS Abstracts; Biotechnology and Bioengineering Abstracts KW - Chronic myeloid leukemia KW - Tumor suppressor genes KW - Data processing KW - Gene therapy KW - Oncology KW - Lymphocytes KW - Tumors KW - Clinical trials KW - Cancer KW - Cytotoxicity KW - Stem cells KW - Oncogenes KW - Case reports KW - Immunogenicity KW - Antigen (tumor-associated) KW - W 30905:Medical Applications KW - V 22350:Immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/744716529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Oncology+Pharmacy+Practice&rft.atitle=Cancer+gene+therapy+update&rft.au=Smith%2C+Judith+A%3BGoldspiel%2C+Barry+R&rft.aulast=Smith&rft.aufirst=Judith&rft.date=1999-03-01&rft.volume=5&rft.issue=1&rft.spage=7&rft.isbn=&rft.btitle=&rft.title=Journal+of+Oncology+Pharmacy+Practice&rft.issn=10781552&rft_id=info:doi/10.1177%2F107815529900500101 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-06-01 N1 - Number of references - 101 N1 - Last updated - 2013-05-31 N1 - SubjectsTermNotLitGenreText - Chronic myeloid leukemia; Tumor suppressor genes; Data processing; Gene therapy; Oncology; Tumors; Lymphocytes; Clinical trials; Cancer; Stem cells; Cytotoxicity; Oncogenes; Case reports; Immunogenicity; Antigen (tumor-associated) DO - http://dx.doi.org/10.1177/107815529900500101 ER - TY - JOUR T1 - Toxicology and carcinogenesis studies of pentachlorophenol in rats. AN - 69756891; 10330679 AB - Pentachlorophenol (PCP) has been used as an herbicide, algaecide, defoliant, wood preservative, germicide, fungicide, and molluscicide. A 28-day toxicity study of PCP in F344/N rats of both sexes was conducted to select dose levels for a carcinogenicity study. Groups of 10 male and 10 female rats were given 0, 200, 400, 800, 1600, or 3200 ppm PCP in feed for 28 days. The incidences of minimal to mild hepatocyte degeneration in males and females exposed to 400 ppm or greater and the incidences of centrilobular hepatocyte hypertrophy in the 3200-ppm groups were increased. For carcinogenicity studies, groups of 50 male and 50 female F344/N rats were fed diets containing 200, 400, or 600 PCP for 2 years. A stop-exposure group of 60 male and 60 female rats received 1000 ppm of PCP in feed for 52 weeks and control feed thereafter for the remainder of the 2-year studies; 10 male and 10 female rats were evaluated at 7 months. Survival of 600-ppm males was significantly greater than that of the controls; survival of all other exposed groups was similar to that of the control groups. Mean body weights of the 400- and 600-ppm groups were generally less than those of the controls throughout the studies. There was no evidence of carcinogenic activity of PCP in male or female rats fed diets containing 200, 400, or 600 ppm for 2 years. Stop-exposure study males and females regained a transitory body weight reduction by the end of the 2 year study, and males had better survival than the controls. At a 7-month interim evaluation, the incidences of centrilobular hypertrophy in stop-exposure males and females exceeded those in the controls. At 2 years, malignant mesothelioma originating from the tunica vaginalis was present in 9 1000-ppm males and 1 control male (p = 0.014). Nasal squamous cell carcinomas were present in five 1000-ppm males and 1 control male. This incidence was not significantly increased but exceeded the historical control range (0-4%). Based on the increased incidences of mesotheliomas and nasal tumors, there was some evidence of carcinogenic activity of PCP in male rats given a diet containing 1000 ppm for 1 year followed by control diet for 1 year. There was no evidence of PCP carcinogenic activity in stop-exposure female rats. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Chhabra, R S AU - Maronpot, R M AU - Bucher, J R AU - Haseman, J K AU - Toft, J D AU - Hejtmancik, M R AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 14 EP - 20 VL - 48 IS - 1 SN - 1096-6080, 1096-6080 KW - Environmental Pollutants KW - 0 KW - Pentachlorophenol KW - D9BSU0SE4T KW - Index Medicus KW - Animals KW - Drug Administration Schedule KW - Liver -- pathology KW - Testis -- pathology KW - Mesothelioma -- chemically induced KW - Testicular Neoplasms -- chemically induced KW - Rats KW - Rats, Inbred F344 KW - Hypertrophy -- pathology KW - Survival Rate KW - Liver -- drug effects KW - Testicular Neoplasms -- pathology KW - Nose Neoplasms -- pathology KW - Body Weight -- drug effects KW - Carcinogenicity Tests KW - Nose Neoplasms -- chemically induced KW - Mesothelioma -- pathology KW - Female KW - Male KW - Environmental Pollutants -- toxicity KW - Pentachlorophenol -- administration & dosage KW - Pentachlorophenol -- toxicity KW - Environmental Pollutants -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69756891?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Toxicology+and+carcinogenesis+studies+of+pentachlorophenol+in+rats.&rft.au=Chhabra%2C+R+S%3BMaronpot%2C+R+M%3BBucher%2C+J+R%3BHaseman%2C+J+K%3BToft%2C+J+D%3BHejtmancik%2C+M+R&rft.aulast=Chhabra&rft.aufirst=R&rft.date=1999-03-01&rft.volume=48&rft.issue=1&rft.spage=14&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-18 N1 - Date created - 1999-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of hepatocellular resistance and susceptibility to styrene toxicity in B6C3F1 mice. AN - 69755788; 10330692 AB - Short-term inhalation exposure of B6C3F1 mice to styrene causes necrosis of centrilobular (CL) hepatocytes. However, in spite of continued exposure, the necrotic parenchyma is rapidly regenerated, indicating resistance by regenerated cells to styrene toxicity. These studies were conducted to test the hypothesis that resistance to repeated styrene exposure is due to sustained cell proliferation, with production of hepatocytes that have reduced metabolic capacity. Male mice were exposed to air or 500 ppm styrene (6 h/day); hepatotoxicity was evaluated by microscopic examination, serum liver enzyme levels, and bromodeoxyuridine (BrdU)-labeling index (LI). Metabolism was assessed by measurement of blood styrene and styrene oxide. Both single and repeated exposures to styrene resulted in mortality by Day 2; in mice that survived, there was CL necrosis with elevated BrdU LI at Day 6, and complete restoration of the necrotic parenchyma by Day 15. The BrdU LI in mice given a single exposure had returned to control levels by Day 15. Re-exposure of these mice on Day 15 resulted in additional mortality and hepatocellular necrosis, indicating that regenerated CL cells were again susceptible to the cytolethal effect of styrene following a 14-day recovery. However, in mice repeatedly exposed to styrene for 14 days, the BrdU LI remained significantly increased on Day 15, with preferential labeling of CL hepatocytes with enlarged nuclei (karyomegaly). If repeated exposures were followed by a 10-day recovery period, CL karyomegaly persisted, but the BrdU LI returned to control level and CL hepatocytes became susceptible again to styrene toxicity as demonstrated by additional mortality and acute necrosis after a challenge exposure. These findings indicated a requirement for continued styrene exposure and DNA synthesis in order to maintain this resistant phenotype. Analyses of proliferating-cell nuclear-antigen (PCNA) labeling were conducted to further characterize the cell cycle kinetics of these hepatocytes. The proportion of cells in S-phase was increased by repeated exposure. However, PCNA analysis also revealed an even larger increase in the G1 cell compartment with repeated exposures, without a concurrent increase in G2 phase or in mitotic cell numbers. These data indicate that resistance to styrene-induced necrosis under conditions of repeated exposure is not due to sustained cell turnover and production of new, metabolically inactive cells, but rather is due to some other, as yet unknown, protective phenotype of the regenerated cells. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Mahler, J F AU - Price, H C AU - O'Connor, R W AU - Wilson, R F AU - Eldridge, S R AU - Moorman, M P AU - Morgan, D L AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 123 EP - 133 VL - 48 IS - 1 SN - 1096-6080, 1096-6080 KW - Proliferating Cell Nuclear Antigen KW - 0 KW - Styrene KW - 44LJ2U959V KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Necrosis KW - Blood Chemical Analysis KW - Survival Rate KW - Cell Division -- physiology KW - Cell Division -- drug effects KW - Proliferating Cell Nuclear Antigen -- analysis KW - Mice KW - Administration, Inhalation KW - Male KW - Immunoenzyme Techniques KW - Bromodeoxyuridine -- metabolism KW - Chemical and Drug Induced Liver Injury -- blood KW - Liver Regeneration -- drug effects KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury -- etiology KW - Chemical and Drug Induced Liver Injury -- pathology KW - Liver -- drug effects KW - Liver -- metabolism KW - Styrene -- blood KW - Styrene -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69755788?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Characterization+of+hepatocellular+resistance+and+susceptibility+to+styrene+toxicity+in+B6C3F1+mice.&rft.au=Mahler%2C+J+F%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BWilson%2C+R+F%3BEldridge%2C+S+R%3BMoorman%2C+M+P%3BMorgan%2C+D+L&rft.aulast=Mahler&rft.aufirst=J&rft.date=1999-03-01&rft.volume=48&rft.issue=1&rft.spage=123&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-18 N1 - Date created - 1999-06-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of NAD:arginine ADP-ribosyltransferases. AN - 69753180; 10331646 AB - NAD:arginine mono-ADP-ribosyltransferases catalyze the transfer of ADP-ribose from NAD to the guanidino group of arginine on a target protein. Deduced amino acid sequences of one family (ART1) of mammalian ADP-ribosyltransferases, cloned from muscle and lymphocytes, show hydrophobic amino and carboxyl termini consistent with glycosylphosphatidylinositol (GPI)-anchored proteins. The proteins, overexpressed in mammalian cells transfected with the transferase cDNAs, are released from the cell surface with phosphatidylinositol-specific phospholipase C (PI-PLC), and display immunological and biochemical characteristics consistent with a cell surface, GPI-anchored protein. In contrast, the deduced amino acid sequence of a second family (ART5) of transferases, cloned from murine lymphoma cells and expressed in high abundance in testis, displays a hydrophobic amino terminus, consistent with a signal sequence, but lacks a hydrophobic signal sequence at its carboxyl terminus, suggesting that the protein is destined for export. Consistent with the surface localization of the GPI-linked transferases, multiple surface substrates have been identified in myotubes and activated lymphocytes, and, notably, include integrin alpha subunits. Similar to the bacterial toxin ADP-ribosyltransferases, the mammalian transferases contain the characteristic domains involved in NAD binding and ADP-ribose transfer, including a highly acidic region near the carboxy terminus, which, when disrupted by in vitro mutagenesis, results in a loss of enzymatic activity. The carboxyl half of the protein, synthesized as a fusion protein in E. coli, possessed NADase, but not ADP-ribosyltransferase activity. These findings are consistent with the existence at the carboxyl terminus of ART1 of a catalytically active domain, capable of hydrolyzing NAD, but not of transferring ADP-ribose to a guanidino acceptor. JF - Molecular and cellular biochemistry AU - Moss, J AU - Balducci, E AU - Cavanaugh, E AU - Kim, H J AU - Konczalik, P AU - Lesma, E A AU - Okazaki, I J AU - Park, M AU - Shoemaker, M AU - Stevens, L A AU - Zolkiewska, A AD - Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1590, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 109 EP - 113 VL - 193 IS - 1-2 SN - 0300-8177, 0300-8177 KW - GPI-Linked Proteins KW - 0 KW - Proteins KW - ADP Ribose Transferases KW - EC 2.4.2.- KW - Pentosyltransferases KW - ART1 protein, human KW - EC 2.4.2.31 KW - ART5 protein, mouse KW - Index Medicus KW - Animals KW - Protein Structure, Secondary KW - Humans KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Sequence Homology, Amino Acid KW - Pentosyltransferases -- genetics KW - ADP Ribose Transferases -- chemistry KW - Proteins -- chemistry KW - Pentosyltransferases -- chemistry KW - Proteins -- genetics KW - ADP Ribose Transferases -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69753180?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biochemistry&rft.atitle=Characterization+of+NAD%3Aarginine+ADP-ribosyltransferases.&rft.au=Moss%2C+J%3BBalducci%2C+E%3BCavanaugh%2C+E%3BKim%2C+H+J%3BKonczalik%2C+P%3BLesma%2C+E+A%3BOkazaki%2C+I+J%3BPark%2C+M%3BShoemaker%2C+M%3BStevens%2C+L+A%3BZolkiewska%2C+A&rft.aulast=Moss&rft.aufirst=J&rft.date=1999-03-01&rft.volume=193&rft.issue=1-2&rft.spage=109&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biochemistry&rft.issn=03008177&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-09 N1 - Date created - 1999-08-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A Lewis(y) epitope mimicking peptide induces anti-Lewis(y) immune responses in rabbits and mice. AN - 69741448; 10231713 AB - Lewis(y) carbohydrate antigens are abundant on the surface of many carcinomas. Mab B3 directed against this carbohydrate antigen has been used to make an immunotoxin that is very cytotoxic to cancer cells expressing the Lewis(y) antigen. Mab B3 was also used to screen a phage-displayed peptide library and identified a peptide mimicking the Lewis(y) epitope. In this report, we demonstrate that the Lewis(y) epitope-mimicking peptide induces anti-Lewis(y)immune responses in both rabbits and mice. In addition, Lewis(y) antigens induce anti-peptide immune responses. These results indicate that carbohydrate-mimicking peptides provide a novel strategy to elicit immune responses for tumor-associated carbohydrates. JF - The journal of peptide research : official journal of the American Peptide Society AU - Lou, Q AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 252 EP - 260 VL - 53 IS - 3 SN - 1397-002X, 1397-002X KW - Antibodies, Monoclonal KW - 0 KW - Epitopes KW - Histocompatibility Antigens Class II KW - Lewis Blood-Group System KW - Peptide Library KW - Index Medicus KW - Animals KW - Dose-Response Relationship, Drug KW - Enzyme-Linked Immunosorbent Assay KW - Rabbits KW - Mice KW - Mice, Inbred BALB C KW - Immunization KW - Female KW - Lewis Blood-Group System -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69741448?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+journal+of+peptide+research+%3A+official+journal+of+the+American+Peptide+Society&rft.atitle=A+Lewis%28y%29+epitope+mimicking+peptide+induces+anti-Lewis%28y%29+immune+responses+in+rabbits+and+mice.&rft.au=Lou%2C+Q%3BPastan%2C+I&rft.aulast=Lou&rft.aufirst=Q&rft.date=1999-03-01&rft.volume=53&rft.issue=3&rft.spage=252&rft.isbn=&rft.btitle=&rft.title=The+journal+of+peptide+research+%3A+official+journal+of+the+American+Peptide+Society&rft.issn=1397002X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-14 N1 - Date created - 1999-07-14 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Phorbol ester exposure activates an AP-1-mediated increase in ERCC-1 messenger RNA expression in human ovarian tumor cells. AN - 69737781; 10228559 AB - ERCC-1 is an essential gene in the nucleotide excision repair pathway, and may be essential for life. However, the mechanism of transcriptional activation and regulation of ERCC-1 gene expression is unclear. We therefore investigated the effect of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the ERCC-1 gene in A2780/CP70 human ovarian carcinoma cells. TPA induced a four- to sixfold increase in steady-state ERCC-1 messenger RNA (mRNA) levels that was time- and concentration-dependent. Nuclear run-on experiments demonstrated that the rate of transcription of ERCC-1 was approximately 2.8-fold higher in TPA-treated cells than in the controls. TPA stimulation of A2780/CP70 cells also resulted in a rapid but transient induction of c-jun and c-fos as determined by Northern and Western blot analyses, which peaked about 2 h before the peak in ERCC-1 expression. Electrophoretic mobility shift assays of nuclear extracts from TPA-treated cells revealed an increase in DNA-binding activity specific for the AP-1-like binding site in the 5'-flanking region of ERCC-1. c-Jun and c-Fos proteins were confirmed to be the components of the activated AP-1 complex by supershift analysis. The increase in AP-1 activity occurs immediately before the increase in ERCC-1 transcription. The increase in AP-1 DNA-binding activity and the increase in ERCC-1 mRNA expression were prevented by pretreatment with cycloheximide. These data suggest that AP-1 may contribute to the upregulation of ERCC-1 in response to TPA in human ovarian cancer cells. JF - Cellular and molecular life sciences : CMLS AU - Li, Q AU - Zhang, L AU - Tsang, B AU - Gardner, K AU - Bostick-Bruton, F AU - Reed, E AD - Developmental Therapeutics Department, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 456 EP - 466 VL - 55 IS - 3 SN - 1420-682X, 1420-682X KW - Amanitins KW - 0 KW - Carcinogens KW - DNA-Binding Proteins KW - Neoplasm Proteins KW - Nucleic Acid Synthesis Inhibitors KW - Protein Synthesis Inhibitors KW - Proteins KW - RNA, Messenger KW - RNA, Neoplasm KW - Transcription Factor AP-1 KW - Cycloheximide KW - 98600C0908 KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Nucleic Acid Synthesis Inhibitors -- pharmacology KW - Tumor Cells, Cultured KW - Protein Synthesis Inhibitors -- pharmacology KW - Amanitins -- pharmacology KW - Humans KW - Cycloheximide -- pharmacology KW - Female KW - Binding Sites KW - RNA, Neoplasm -- biosynthesis KW - Carcinogens -- pharmacology KW - Ovarian Neoplasms -- metabolism KW - Transcription, Genetic -- drug effects KW - RNA, Neoplasm -- genetics KW - RNA, Messenger -- genetics KW - Transcription Factor AP-1 -- physiology KW - Gene Expression Regulation, Neoplastic -- drug effects KW - Proteins -- genetics KW - DNA Repair -- drug effects KW - RNA, Messenger -- biosynthesis KW - Ovarian Neoplasms -- pathology KW - Neoplasm Proteins -- genetics KW - Tetradecanoylphorbol Acetate -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69737781?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.atitle=Phorbol+ester+exposure+activates+an+AP-1-mediated+increase+in+ERCC-1+messenger+RNA+expression+in+human+ovarian+tumor+cells.&rft.au=Li%2C+Q%3BZhang%2C+L%3BTsang%2C+B%3BGardner%2C+K%3BBostick-Bruton%2C+F%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=1999-03-01&rft.volume=55&rft.issue=3&rft.spage=456&rft.isbn=&rft.btitle=&rft.title=Cellular+and+molecular+life+sciences+%3A+CMLS&rft.issn=1420682X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-19 N1 - Date created - 1999-05-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Adhesion and signaling proteins spatiotemporally associated with spermiation in the rat. AN - 69735360; 10232655 AB - Spermiation, the process by which late spermatids separate from the Sertoli cell, is disrupted by a number of toxicants. In this study, we used immunohistochemistry (IHC) to identify some of the proteins associated with the spermatid-Sertoli junction. We confirmed the presence of tubulin, actin, and vinculin at the luminal edge of the seminiferous tubule, and we determined that paxillin is also present here. In other cell types, these proteins have been reported to colocalize with beta integrins. Numerous attempts to identify beta integrins by IHC and by use of Western blots were unsuccessful. Clear evidence was found for the presence of N-cadherin and its associated intracellular proteins: beta-catenin, pp120, desmoglein, pp60(src), and Csk. In addition, N-cadherin and desmoglein were found around spermatids retained by the epithelium. From these data and previous literature reports, we propose a hypothetical model for spermatid adhesion and the control of that adhesion, thus providing a framework for hypotheses on the steps involved in the complex process of spermiation in rat testes. JF - Journal of andrology AU - Wine, R N AU - Chapin, R E AD - Reproductive Toxicology Group, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. PY - 1999 SP - 198 EP - 213 VL - 20 IS - 2 SN - 0196-3635, 0196-3635 KW - Cell Adhesion Molecules KW - 0 KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Blotting, Western KW - Immunohistochemistry KW - Male KW - Spermatozoa -- physiology KW - Cell Adhesion Molecules -- physiology KW - Signal Transduction UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69735360?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+andrology&rft.atitle=Adhesion+and+signaling+proteins+spatiotemporally+associated+with+spermiation+in+the+rat.&rft.au=Wine%2C+R+N%3BChapin%2C+R+E&rft.aulast=Wine&rft.aufirst=R&rft.date=1999-03-01&rft.volume=20&rft.issue=2&rft.spage=198&rft.isbn=&rft.btitle=&rft.title=Journal+of+andrology&rft.issn=01963635&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-09 N1 - Date created - 1999-07-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chronic caffeine exposure potentiates nicotine self-administration in rats. AN - 69730133; 10229056 AB - The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150-180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking. JF - Psychopharmacology AU - Shoaib, M AU - Swanner, L S AU - Yasar, S AU - Goldberg, S R AD - Preclinical Pharmacology Laboratory, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. spjumos@iop.bpmf.ac.uk Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 327 EP - 333 VL - 142 IS - 4 SN - 0033-3158, 0033-3158 KW - Caffeine KW - 3G6A5W338E KW - Nicotine KW - 6M3C89ZY6R KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Rats KW - Dopamine -- secretion KW - Animals KW - Rats, Sprague-Dawley KW - Self Administration KW - Motor Activity -- drug effects KW - Drug Synergism KW - Male KW - Caffeine -- administration & dosage KW - Reinforcement (Psychology) KW - Nicotine -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69730133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Psychopharmacology&rft.atitle=Chronic+caffeine+exposure+potentiates+nicotine+self-administration+in+rats.&rft.au=Shoaib%2C+M%3BSwanner%2C+L+S%3BYasar%2C+S%3BGoldberg%2C+S+R&rft.aulast=Shoaib&rft.aufirst=M&rft.date=1999-03-01&rft.volume=142&rft.issue=4&rft.spage=327&rft.isbn=&rft.btitle=&rft.title=Psychopharmacology&rft.issn=00333158&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-10 N1 - Date created - 1999-06-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Alcohol and the family: opportunities for prevention. AN - 69728760; 10225483 AB - The intent of this supplement issue is to present current research on the role of families in the development of alcohol-related risk, to assess the potential of efficacy of family-based preventive interventions and to identify new directions for research. The National Institute on Alcohol Abuse and Alcoholism convened a working group of family and alcohol researchers in December 1996, to address these issues in a 2-day meeting. The articles presented in this supplement reflect the major presentations and discussions at that meeting. There is theoretical and empirical support for the potential efficacy of universal and selective family-based preventive interventions for children. Studies testing the generalizability of intervention approaches are especially needed. Some additional preintervention research is needed, but should be directed toward questions with direct applicability to intervention development. Relatively little is known about family influences on adult risk, and the potential efficacy of family interventions for adults is not known at this time. JF - Journal of studies on alcohol. Supplement AU - Boyd, G M AD - Prevention Research Branch, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 5 EP - 9 VL - 13 SN - 0363-468X, 0363-468X KW - Index Medicus KW - Child Behavior -- psychology KW - Humans KW - Adult KW - Child KW - Adolescent KW - Alcoholism -- etiology KW - Alcoholism -- psychology KW - Alcoholism -- prevention & control KW - Family -- psychology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69728760?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+studies+on+alcohol.+Supplement&rft.atitle=Alcohol+and+the+family%3A+opportunities+for+prevention.&rft.au=Boyd%2C+G+M&rft.aulast=Boyd&rft.aufirst=G&rft.date=1999-03-01&rft.volume=13&rft.issue=&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Journal+of+studies+on+alcohol.+Supplement&rft.issn=0363468X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-15 N1 - Date created - 1999-06-15 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure received from application of animal insecticides. AN - 69724449; 10222571 AB - Part of an investigation of data collection methods in epidemiologic studies of farmers evaluated exposures received by farmers from the application of insecticides to animals. Twenty farmers were monitored during a normal application using a fluorescent dye surrogate for the active ingredient (AI). Two exposure measures were estimated, AI concentration and the time-weighted average for the application period (TWAa). Four application methods were used: high- (n = 5) and low-pressure (n = 3) spraying, backpack (n = 2) and pour-on (n = 10). The two farmers using a backpack sprayer had nondetectable levels of dye. Only two of the farmers using the pour-on method had detectable dye levels, but these levels were high. All of the low- and high-pressure sprayers had detectable amounts of dye. Multiple layers of clothing, gloves, and boots (n = 10) were associated with a low mean AI concentration for the exposed farmers (18 micrograms) and more than two-thirds of the farmers wearing this amount of clothing had nondetectable exposures. In contrast, clothing providing little or no protection was associated with a significantly higher (p < 0.01) average AI concentration (4420 micrograms), and less than a third of the farmers with this degree of protection had nondetectable exposures. Poor work practices (leaking equipment, contact with wet animals or fences, and back splash) were associated with statistically higher exposure levels (p < 0.01) than the absence of such practices. There was a moderate statistically significant association between AI concentration and TWAa with total volume of the AI/dye/water mixture using the Spearman coefficient. Time was significantly inversely proportional to the two exposure measures. The association between the two exposure measures and AI volume was not significant. JF - American Industrial Hygiene Association journal AU - Stewart, P AU - Fears, T AU - Nicholson, H F AU - Kross, B C AU - Ogilvie, L K AU - Zahm, S H AU - Ward, M H AU - Blair, A AD - Division of Cancer Etiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7240, USA. PY - 1999 SP - 208 EP - 212 VL - 60 IS - 2 SN - 0002-8894, 0002-8894 KW - Fluorescent Dyes KW - 0 KW - Insecticides KW - Index Medicus KW - Videotape Recording KW - Risk Factors KW - Humans KW - Iowa KW - Statistics, Nonparametric KW - Clothing KW - Occupational Exposure -- prevention & control KW - Animal Husbandry -- methods KW - Animal Husbandry -- instrumentation KW - Insecticides -- analysis KW - Occupational Exposure -- analysis KW - Environmental Monitoring -- methods UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69724449?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+Industrial+Hygiene+Association+journal&rft.atitle=Exposure+received+from+application+of+animal+insecticides.&rft.au=Stewart%2C+P%3BFears%2C+T%3BNicholson%2C+H+F%3BKross%2C+B+C%3BOgilvie%2C+L+K%3BZahm%2C+S+H%3BWard%2C+M+H%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=1999-03-01&rft.volume=60&rft.issue=2&rft.spage=208&rft.isbn=&rft.btitle=&rft.title=American+Industrial+Hygiene+Association+journal&rft.issn=00028894&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-13 N1 - Date created - 1999-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Drugs of abuse and the brain. AN - 69720754; 10220804 AB - New insights into our understanding of drug abuse and addiction have revealed that the desire to use drugs and the process of addiction depend on effects on brain function. Drugs of abuse have been hypothesized to produce their rewarding effects by neuropharmacological actions on a common brain reward circuit called the extended amygdala. The extended amygdala involves the mesolimbic dopamine system and specific subregions of the basal forebrain, such as the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala. The psychomotor stimulants cocaine and amphetamine activate the mesolimbic dopamine system; opiates activate opioid peptide receptors within and independent of the mesolimbic dopamine system. Sedative hypnotics alter multiple neurotransmitter systems in this circuitry, including: 1) gamma aminobutyric acid; 2) dopamine; 3) serotonin; 4) glutamate; and 5) opioid peptides. Nicotine and tetrahydrocannabinol both activate mesolimbic dopamine function and possibly opioid peptide systems in this circuitry. Repeated and prolonged drug abuse leads to compulsive use, and the mechanism for this transition involves, at the behavioral level, a progressive dysregulation of brain reward circuitry and a recruitment of brain stress systems such as corticotropin-releasing factor. The molecular mechanisms of signal transduction in these systems are a likely target for residual changes in that they convey allostatic changes in reward set point, which lead to vulnerability to relapse. JF - Proceedings of the Association of American Physicians AU - Leshner, A I AU - Koob, G F AD - National Institute on Drug Abuse, National Institutes of Health, Rockville, MD, USA. PY - 1999 SP - 99 EP - 108 VL - 111 IS - 2 SN - 1081-650X, 1081-650X KW - Pharmaceutical Preparations KW - 0 KW - Index Medicus KW - Animals KW - Humans KW - Substance-Related Disorders -- physiopathology KW - Brain -- drug effects KW - Brain -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69720754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+Association+of+American+Physicians&rft.atitle=Drugs+of+abuse+and+the+brain.&rft.au=Leshner%2C+A+I%3BKoob%2C+G+F&rft.aulast=Leshner&rft.aufirst=A&rft.date=1999-03-01&rft.volume=111&rft.issue=2&rft.spage=99&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+Association+of+American+Physicians&rft.issn=1081650X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell adhesion molecules in the kidney: from embryo to adult. AN - 69713596; 10213863 AB - Multiple members from every major family of cell adhesion molecules (CAMs) have been implicated in the development, maintenance, or repair of renal tissues and include several isoforms of integrins, cell-bound glycoproteins, cadherins, immunoglobulin cell adhesion molecules, and selectins. In combination, they mediate a variety of cell-basement membrane and cell-cell interactions believed to direct morphogenesis and cell migration and regulate cell growth and apoptosis, in addition to generating a functional barrier for blood filtration and helping manage inflammatory responses in the kidney. The expression of some CAMs is transient during and critical to normal nephrogenesis, varying with specific stages of development, but often ultimately resulting in the constitutive production of other members in mature tissues. While gene-targeting studies have successfully implicated individual CAMs in renal cell functions, e.g. , alpha3beta1 and alpha8beta1 integrins, the loss of others bears no renal phenotype due to redundancy of homologous family members or to the severity of the defect early in embryogenesis. This review summarizes the studies of various CAMs found in normal embryonic or adult kidney, describes their spatiotemporal expression patterns, and discusses their involvement in renal processes. JF - Experimental nephrology AU - Perantoni, A O AD - Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Md., USA. peranton@mail.ncifcrf.gov PY - 1999 SP - 80 EP - 102 VL - 7 IS - 2 SN - 1018-7782, 1018-7782 KW - Cell Adhesion Molecules KW - 0 KW - Integrins KW - Index Medicus KW - Embryo, Mammalian -- physiology KW - Animals KW - Embryonic and Fetal Development KW - Humans KW - Adult KW - Cell Adhesion KW - Kidney -- growth & development KW - Kidney -- embryology KW - Kidney -- physiology KW - Cell Adhesion Molecules -- physiology KW - Integrins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69713596?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+nephrology&rft.atitle=Cell+adhesion+molecules+in+the+kidney%3A+from+embryo+to+adult.&rft.au=Perantoni%2C+A+O&rft.aulast=Perantoni&rft.aufirst=A&rft.date=1999-03-01&rft.volume=7&rft.issue=2&rft.spage=80&rft.isbn=&rft.btitle=&rft.title=Experimental+nephrology&rft.issn=10187782&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-24 N1 - Date created - 1999-08-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors. AN - 69712405; 10217528 AB - 1. A [3H]-resiniferatoxin (RTX) binding assay utilizing rat spinal cord membranes was employed to identify novel vanilloids in a collection of natural products of fungal origin. Of the five active compounds found (scutigeral, acetyl-scutigeral, ovinal, neogrifolin, and methyl-neogrifolin), scutigeral (Ki=19 microM), isolated from the edible mushroom Albatrellus ovinus, was selected for further characterization. 2. Scutigeral induced a dose-dependent 45Ca uptake by rat dorsal root ganglion neurons with an EC50 of 1.6 microM, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine (IC50=5.2 microM). 3. [3H]-RTX binding isotherms were shifted by scutigeral (10-80 microM) in a competitive manner. The Schild plot of the data had a slope of 0.8 and gave an apparent Kd estimate for scutigeral of 32 microM. 4. Although in the above assays scutigeral mimicked capsaicin, it was not pungent on the human tongue up to a dose of 100 nmol per tongue, nor did it provoke protective wiping movements in the rat (up to 100 microM) upon intraocular instillation. 5. In accord with being non-pungent, scutigeral (5 microM) did not elicit a measurable inward current in isolated rat dorsal root ganglion neurons under voltage-clamp conditions. It did, however, reduce the proportion of neurons (from 61 to 15%) that responded to a subsequent capsaicin (1 microM) challenge. In these neurons, scutigeral both delayed (from 27 to 72 s) and diminished (from 5.0 to 1.9 nA) the maximal current evoked by capsaicin. 6. In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids. JF - British journal of pharmacology AU - Szallasi, A AU - Bíró, T AU - Szabó, T AU - Modarres, S AU - Petersen, M AU - Klusch, A AU - Blumberg, P M AU - Krause, J E AU - Sterner, O AD - Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri, USA. szallasi@exchange.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1351 EP - 1358 VL - 126 IS - 6 SN - 0007-1188, 0007-1188 KW - Calcium Radioisotopes KW - 0 KW - Diterpenes KW - Irritants KW - Phenols KW - Receptors, Drug KW - scutigeral KW - Tritium KW - 10028-17-8 KW - resiniferatoxin KW - A5O6P1UL4I KW - capsazepine KW - LFW48MY844 KW - Capsaicin KW - S07O44R1ZM KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Spinal Cord -- metabolism KW - Dose-Response Relationship, Drug KW - Humans KW - Membranes -- metabolism KW - Taste -- drug effects KW - Eye -- drug effects KW - Diterpenes -- metabolism KW - Irritants -- pharmacology KW - Capsaicin -- pharmacology KW - Rats KW - Rats, Sprague-Dawley KW - Patch-Clamp Techniques KW - Cells, Cultured KW - Binding, Competitive KW - Calcium -- pharmacokinetics KW - Membrane Potentials -- drug effects KW - Tongue -- drug effects KW - Capsaicin -- analogs & derivatives KW - Male KW - Female KW - Ganglia, Spinal -- cytology KW - Receptors, Drug -- metabolism KW - Phenols -- pharmacology KW - Ganglia, Spinal -- physiology KW - Neurons -- drug effects KW - Phenols -- metabolism KW - Neurons -- cytology KW - Neurons -- physiology KW - Basidiomycota -- chemistry KW - Ganglia, Spinal -- drug effects KW - Receptors, Drug -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69712405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+pharmacology&rft.atitle=A+non-pungent+triprenyl+phenol+of+fungal+origin%2C+scutigeral%2C+stimulates+rat+dorsal+root+ganglion+neurons+via+interaction+at+vanilloid+receptors.&rft.au=Szallasi%2C+A%3BB%C3%ADr%C3%B3%2C+T%3BSzab%C3%B3%2C+T%3BModarres%2C+S%3BPetersen%2C+M%3BKlusch%2C+A%3BBlumberg%2C+P+M%3BKrause%2C+J+E%3BSterner%2C+O&rft.aulast=Szallasi&rft.aufirst=A&rft.date=1999-03-01&rft.volume=126&rft.issue=6&rft.spage=1351&rft.isbn=&rft.btitle=&rft.title=British+journal+of+pharmacology&rft.issn=00071188&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-22 N1 - Date created - 1999-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Urol. 1997 Dec;158(6):2093-6 [9366319] J Neurosci. 1997 Jun 1;17(11):4101-11 [9151727] Eur J Pharmacol. 1998 Aug 28;356(1):81-9 [9761427] Neuron. 1998 Sep;21(3):531-43 [9768840] Br J Pharmacol Chemother. 1959 Mar;14(1):48-58 [13651579] Arzneimittelforschung. 1975;25(12):1877-81 [1243658] Experientia. 1981 Oct 15;37(10):1063-4 [7308389] Neuroscience. 1987 Oct;23(1):275-89 [3683864] J Neurosci. 1988 Sep;8(9):3208-20 [3171675] Life Sci. 1988;43(17):1385-91 [3185099] Neuroscience. 1989;30(2):515-20 [2747924] Trends Pharmacol Sci. 1990 Aug;11(8):330-3 [2203194] J Pharmacol Exp Ther. 1990 Nov;255(2):923-8 [2243359] Life Sci. 1990;47(16):1399-408 [2174484] Agents Actions. 1990 Nov;31(3-4):329-40 [2128168] Neuroscience. 1991;40(2):513-21 [2027470] Life Sci. 1991;48(19):1863-9 [1645836] J Auton Pharmacol. 1991 Jun;11(3):173-208 [1677008] Pharmacol Rev. 1991 Jun;43(2):143-201 [1852779] Physiol Behav. 1991 Apr;49(4):757-64 [1881981] Arch Intern Med. 1991 Nov;151(11):2225-9 [1953227] Lancet. 1992 May 16;339(8803):1239 [1349978] J Pharmacol Exp Ther. 1992 Sep;262(3):883-8 [1527730] Naunyn Schmiedebergs Arch Pharmacol. 1993 Jan;347(1):84-91 [8446186] Br J Urol. 1993 Jun;71(6):686-91 [8343895] J Pharmacol Exp Ther. 1993 Aug;266(2):678-83 [8355200] Pain. 1993 Nov;55(2):205-15 [7508591] Pharmacol Rev. 1996 Mar;48(1):113-78 [8685245] Neuron. 1996 Jun;16(6):1069-72 [8663982] J Neurophysiol. 1996 Apr;75(4):1503-14 [8727394] J Med Chem. 1996 Aug 2;39(16):3123-31 [8759633] Brain Res Mol Brain Res. 1996 Jan;35(1-2):173-82 [8717353] Pain. 1996 Jan;64(1):191-5 [8867262] Br J Pharmacol. 1996 Sep;119(2):283-90 [8886410] J Neurophysiol. 1996 Sep;76(3):1858-69 [8890298] Eur J Pharmacol. 1996 Mar 28;299(1-3):221-8 [8901026] Neuroscience. 1996 Nov;75(2):495-505 [8931013] Pain. 1996 Dec;68(2-3):195-208 [9121806] Lancet. 1997 Aug 30;350(9078):640-1 [9288055] Nature. 1997 Oct 23;389(6653):816-24 [9349813] Life Sci. 1997;60(10):681-96 [9064473] J Neurosci Methods. 1997 Feb;71(2):191-8 [9128156] Neuroscience. 1998 May;84(2):569-81 [9539227] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prenatal drug exposure and child outcome. Past, present, future. AN - 69709519; 10214540 AB - Scientific study of prenatal drug exposure and child outcome began a period of substantial growth in the 1970s with a focus on exposure to opiates. By the mid-1980s, attention shifted to cocaine. Most of this research has involved cohort studies in which groups of children are followed up longitudinally from birth. Significant progress has been made regarding the assessment of child outcome (greater range of outcome areas and greater specificity of measures) and regarding attention to and analysis of confounding factors that travel with prenatal exposure. As progress has been made, investigators are tackling new and continuing challenges inherent in these complex studies. Considerable effort is being devoted to determining the level of severity of exposure. Interest is increasing regarding the use of neuroimaging assessments as well as the identification of possible biologic and environmental mechanisms underlying associations between prenatal exposure and subtle child outcomes. JF - Clinics in perinatology AU - Smeriglio, V L AU - Wilcox, H C AD - Center on AIDS and Other Medical Consequences of Drug Abuse, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland, USA. vs24o@nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1 EP - 16 VL - 26 IS - 1 SN - 0095-5108, 0095-5108 KW - Index Medicus KW - Infant KW - Environment KW - Cocaine-Related Disorders KW - Humans KW - Diagnostic Imaging KW - Confounding Factors (Epidemiology) KW - Cohort Studies KW - Infant, Newborn KW - Brain Diseases -- diagnosis KW - Opioid-Related Disorders KW - Longitudinal Studies KW - Female KW - Pregnancy KW - Pregnancy Complications KW - Substance-Related Disorders KW - Child Development KW - Prenatal Exposure Delayed Effects KW - Pregnancy Outcome UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69709519?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Clinics+in+perinatology&rft.atitle=Prenatal+drug+exposure+and+child+outcome.+Past%2C+present%2C+future.&rft.au=Smeriglio%2C+V+L%3BWilcox%2C+H+C&rft.aulast=Smeriglio&rft.aufirst=V&rft.date=1999-03-01&rft.volume=26&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Clinics+in+perinatology&rft.issn=00955108&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-08 N1 - Date created - 1999-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Apoptosis in a canine model of acute Chagasic myocarditis. AN - 69694421; 10198189 AB - Histologic, ultrastructural and nick end labeling studies were made to evaluate the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to experimental infection with T. cruzi. The best results for the detection of apoptosis by nick end labeling were obtained by a method combining the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated deoxyuridine triphosphate, followed by counterstaining of DNA with 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes; (2) endothelial cells of capillaries and venules: (3) immune effector cells, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracellular forms of T. cruzi. The apoptosis in myocytes and endothelial cells affected cells that were not infected by T. cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune effector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apoptosis in T. cruzi confirms the results of other studies showing that this phenomenon occurs during the differentiation of trypomastigotes in vitro. Thus, apoptosis constitutes an important and multifactorial event in the pathogenesis of acute Chagasic myocarditis. JF - Journal of molecular and cellular cardiology AU - Zhang, J AU - Andrade, Z A AU - Yu, Z X AU - Andrade, S G AU - Takeda, K AU - Sadirgursky, M AU - Ferrans, V J AD - Pathology Section, National Heart, Lung & Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 581 EP - 596 VL - 31 IS - 3 SN - 0022-2828, 0022-2828 KW - Index Medicus KW - Animals KW - Endothelium, Vascular -- metabolism KW - Trypanosoma cruzi -- ultrastructure KW - Myocardium -- pathology KW - Dogs KW - Lymphocytes -- metabolism KW - Myocardium -- ultrastructure KW - Lymphocytes -- ultrastructure KW - Endothelium, Vascular -- ultrastructure KW - DNA Fragmentation KW - In Situ Nick-End Labeling -- methods KW - Chagas Cardiomyopathy -- pathology KW - Apoptosis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69694421?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+and+cellular+cardiology&rft.atitle=Apoptosis+in+a+canine+model+of+acute+Chagasic+myocarditis.&rft.au=Zhang%2C+J%3BAndrade%2C+Z+A%3BYu%2C+Z+X%3BAndrade%2C+S+G%3BTakeda%2C+K%3BSadirgursky%2C+M%3BFerrans%2C+V+J&rft.aulast=Zhang&rft.aufirst=J&rft.date=1999-03-01&rft.volume=31&rft.issue=3&rft.spage=581&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+and+cellular+cardiology&rft.issn=00222828&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-08 N1 - Date created - 1999-07-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Parallels to early onset alcohol use in the relationship of early onset smoking with drug use and DSM-IV drug and depressive disorders: findings from the National Longitudinal Epidemiologic Survey. AN - 69676847; 10195827 AB - This paper endeavored to determine (1) if early onset of regular tobacco use is as predictive of drug use and depressive disorders as it is of alcohol use disorders; and (2) if a biological commonality, as measured by a family history of alcoholism and both early onset and severity of disease, among all three disorders can be evidenced in a large nationally representative sample. Prevalences of lifetime drug use, drug abuse and dependence, and major depressive disorders, as well as indices of their severity, were compared among smoking groups defined by age at onset of regular tobacco use and among nonsmokers. Linear logistic regression analyses, controlling for important covariates, including a family history positive for alcoholism, were conducted to assess the relationship between age at smoking onset and drug use, abuse and dependence, as well as depressive disorders. Both objectives were met. Moreover, results suggest that smoking may play an equally, if not even more, insidious role than drinking in the use and development of dependence on illicit substances and depression. JF - Alcoholism, clinical and experimental research AU - Hanna, E Z AU - Grant, B F AD - National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA. ehanna@willco.niaaa.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 513 EP - 522 VL - 23 IS - 3 SN - 0145-6008, 0145-6008 KW - Index Medicus KW - Psychiatric Status Rating Scales KW - Age of Onset KW - Tobacco Use Disorder -- epidemiology KW - Risk Factors KW - Humans KW - Tobacco Use Disorder -- genetics KW - Adult KW - Diagnosis, Dual (Psychiatry) KW - Tobacco Use Disorder -- psychology KW - Longitudinal Studies KW - Adolescent KW - United States -- epidemiology KW - Male KW - Female KW - Depressive Disorder -- epidemiology KW - Depressive Disorder -- psychology KW - Alcohol Drinking -- psychology KW - Depressive Disorder -- genetics KW - Smoking -- psychology KW - Alcohol Drinking -- genetics KW - Substance-Related Disorders -- psychology KW - Smoking -- genetics KW - Alcohol Drinking -- epidemiology KW - Substance-Related Disorders -- genetics KW - Smoking -- epidemiology KW - Substance-Related Disorders -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69676847?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Parallels+to+early+onset+alcohol+use+in+the+relationship+of+early+onset+smoking+with+drug+use+and+DSM-IV+drug+and+depressive+disorders%3A+findings+from+the+National+Longitudinal+Epidemiologic+Survey.&rft.au=Hanna%2C+E+Z%3BGrant%2C+B+F&rft.aulast=Hanna&rft.aufirst=E&rft.date=1999-03-01&rft.volume=23&rft.issue=3&rft.spage=513&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-25 N1 - Date created - 1999-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor. AN - 69664213; 10188874 AB - The effect of the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a noncompetitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent. JF - British journal of cancer AU - Ciolino, H P AU - Yeh, G C AD - Cellular Defense and Carcinogenesis Section, Basic Research Laboratory, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, NIH, MD 21702-1201, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1340 EP - 1346 VL - 79 IS - 9-10 SN - 0007-0920, 0007-0920 KW - 7,12-dimethylbenz(a)anthracene-DNA adduct KW - 0 KW - Carcinogens KW - DNA Adducts KW - Enzyme Inhibitors KW - Flavonoids KW - RNA, Messenger KW - Receptors, Aryl Hydrocarbon KW - galangin KW - 142FWE6ECS KW - 9,10-Dimethyl-1,2-benzanthracene KW - 57-97-6 KW - Cytochrome P-450 CYP1A1 KW - EC 1.14.14.1 KW - Dimethyl Sulfoxide KW - YOW8V9698H KW - Index Medicus KW - Tumor Cells, Cultured -- metabolism KW - RNA, Messenger -- metabolism KW - Tumor Cells, Cultured -- drug effects KW - Humans KW - Dimethyl Sulfoxide -- metabolism KW - Reverse Transcriptase Polymerase Chain Reaction KW - DNA Adducts -- metabolism KW - Cell Division KW - Cytochrome P-450 CYP1A1 -- genetics KW - Carcinogens -- metabolism KW - 9,10-Dimethyl-1,2-benzanthracene -- analogs & derivatives KW - Receptors, Aryl Hydrocarbon -- agonists KW - Enzyme Inhibitors -- pharmacology KW - Cytochrome P-450 CYP1A1 -- metabolism KW - Flavonoids -- pharmacology KW - 9,10-Dimethyl-1,2-benzanthracene -- metabolism KW - Cytochrome P-450 CYP1A1 -- antagonists & inhibitors KW - Receptors, Aryl Hydrocarbon -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69664213?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=The+flavonoid+galangin+is+an+inhibitor+of+CYP1A1+activity+and+an+agonist%2Fantagonist+of+the+aryl+hydrocarbon+receptor.&rft.au=Ciolino%2C+H+P%3BYeh%2C+G+C&rft.aulast=Ciolino&rft.aufirst=H&rft.date=1999-03-01&rft.volume=79&rft.issue=9-10&rft.spage=1340&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-15 N1 - Date created - 1999-04-15 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochem Pharmacol. 1998 Jul 15;56(2):197-206 [9698073] Food Chem Toxicol. 1995 Dec;33(12):1061-80 [8847003] Drug Metab Dispos. 1996 Feb;24(2):232-7 [8742236] J Am Diet Assoc. 1996 Oct;96(10):1027-39 [8841165] Nutr Cancer. 1996;26(2):167-81 [8875554] Toxicology. 1996 Nov 15;114(1):19-27 [8931757] Prostaglandins Leukot Essent Fatty Acids. 1996 Dec;55(6):441-9 [9014224] Cancer Lett. 1997 Jan 30;112(2):127-33 [9066718] Crit Rev Toxicol. 1997 Mar;27(2):109-34 [9099515] Cancer Lett. 1997 Mar 19;114(1-2):139-40 [9103273] Drug Metab Dispos. 1997 May;25(5):617-22 [9152602] Life Sci. 1997;60(24):2157-63 [9188758] Biochem Mol Biol Int. 1997 Jun;42(1):35-44 [9192083] Biochim Biophys Acta. 1997 Jun 6;1335(3):335-42 [9202196] Prostate. 1997 Jul 1;32(2):122-8 [9215400] Biomed Pharmacother. 1997;51(8):305-10 [9436520] Arch Toxicol Suppl. 1998;20:237-48 [9442297] Xenobiotica. 1998 Feb;28(2):117-26 [9522437] Cancer Res. 1998 Jun 1;58(11):2366-74 [9622076] Environ Health Perspect. 1998 Feb;106(2):85-92 [9435150] Anal Biochem. 1976 May 7;72:248-54 [942051] World Rev Nutr Diet. 1976;24:117-91 [790781] Cancer Res. 1981 Jan;41(1):67-72 [7448777] Cancer Res. 1985 Jan;45(1):1-8 [3880665] Arch Biochem Biophys. 1985 Jul;240(1):345-57 [3925883] Proc Natl Acad Sci U S A. 1986 Nov;83(21):8044-8 [3464941] Methods Enzymol. 1987;152:704-20 [2889129] Nucleic Acids Res. 1988 Feb 11;16(3):1215 [3344216] Cancer Res. 1988 Oct 15;48(20):5754-8 [3139283] J Natl Cancer Inst. 1990 Jul 4;82(13):1113-8 [2359137] Biochem Pharmacol. 1993 Mar 9;45(5):1129-36 [8384853] Carcinogenesis. 1994 Apr;15(4):725-32 [8149487] Biochim Biophys Acta. 1994 Apr 13;1205(2):325-35 [8155716] J Biol Chem. 1994 Apr 22;269(16):11751-9 [7909315] Biochem Pharmacol. 1994 Oct 7;48(7):1437-45 [7945444] Toxicol Appl Pharmacol. 1995 Jan;130(1):73-78 [7839372] Anal Biochem. 1994 Oct;222(1):217-23 [7856852] Carcinogenesis. 1995 Mar;16(3):437-41 [7697795] J Nutr. 1995 Jul;125(7):1911-22 [7616308] Arch Biochem Biophys. 1995 Aug 20;321(2):405-12 [7646066] Carcinogenesis. 1995 Nov;16(11):2833-40 [7586206] Eur J Pharmacol. 1995 Oct 6;293(3):191-205 [8666036] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protein kinase C-epsilon plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells. AN - 69661940; 10099832 AB - In this study, we examined the role of specific protein kinase C (PKC) isoforms in the differentiation of PC12 cells in response to nerve growth factor (NGF) and epidermal growth factor (EGF). PC12 cells express PKC-alpha, -beta, -gamma, -delta, -epsilon, -mu, and -zeta. For PKC-delta, -epsilon, and -zeta, NGF and EGF exerted differential effects on translocation. Unlike overexpression of PKC-alpha and -delta, overexpression of PKC-epsilon caused enhanced neurite outgrowth in response to NGF. In the PKC-epsilon-overexpressing cells, EGF also dramatically induced neurite outgrowth, arrested cell proliferation, and induced a sustained phosphorylation of mitogen-activated protein kinase (MAPK), in contrast to its mitogenic effects on control cells or cells overexpressing PKC-alpha and -delta. The induction of neurite outgrowth by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells overexpressing a PKC-epsilon dominant negative mutant, NGF induced reduced neurite outgrowth and a more transient phosphorylation of MAPK than in controls. Our results suggest an important role for PKC-epsilon in neurite outgrowth in PC12 cells, probably via activation of the MAPK pathway. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Brodie, C AU - Bogi, K AU - Acs, P AU - Lazarovici, P AU - Petrovics, G AU - Anderson, W B AU - Blumberg, P M AD - Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 183 EP - 191 VL - 10 IS - 3 SN - 1044-9523, 1044-9523 KW - 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one KW - 0 KW - Enzyme Inhibitors KW - Flavonoids KW - Nerve Growth Factors KW - Epidermal Growth Factor KW - 62229-50-9 KW - Protein Kinase C KW - EC 2.7.11.13 KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Rats KW - Immunoblotting KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Animals KW - Phosphorylation KW - Enzyme Inhibitors -- pharmacology KW - Mice KW - Flavonoids -- pharmacology KW - Time Factors KW - Translocation, Genetic KW - PC12 Cells KW - Mutagenesis KW - Cell Division KW - Neurites -- drug effects KW - Nerve Growth Factors -- physiology KW - Protein Kinase C -- physiology KW - Neurites -- physiology KW - Epidermal Growth Factor -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69661940?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Protein+kinase+C-epsilon+plays+a+role+in+neurite+outgrowth+in+response+to+epidermal+growth+factor+and+nerve+growth+factor+in+PC12+cells.&rft.au=Brodie%2C+C%3BBogi%2C+K%3BAcs%2C+P%3BLazarovici%2C+P%3BPetrovics%2C+G%3BAnderson%2C+W+B%3BBlumberg%2C+P+M&rft.aulast=Brodie&rft.aufirst=C&rft.date=1999-03-01&rft.volume=10&rft.issue=3&rft.spage=183&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-04 N1 - Date created - 1999-06-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors. AN - 69647711; 10093040 AB - Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x3 subcutaneously with the specific Ras peptide along with Detox adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 micrograms). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy. JF - Journal of immunotherapy (Hagerstown, Md. : 1997) AU - Khleif, S N AU - Abrams, S I AU - Hamilton, J M AU - Bergmann-Leitner, E AU - Chen, A AU - Bastian, A AU - Bernstein, S AU - Chung, Y AU - Allegra, C J AU - Schlom, J AD - Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 155 EP - 165 VL - 22 IS - 2 SN - 1524-9557, 1524-9557 KW - Cancer Vaccines KW - 0 KW - ras Proteins KW - EC 3.6.5.2 KW - Index Medicus KW - AIDS/HIV KW - Lymphocyte Activation KW - CD8-Positive T-Lymphocytes -- immunology KW - Humans KW - Adult KW - CD4-Positive T-Lymphocytes -- immunology KW - Aged KW - Middle Aged KW - Vaccination KW - Mutation KW - Cancer Vaccines -- immunology KW - ras Proteins -- immunology KW - Neoplasms -- therapy KW - Neoplasms -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69647711?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.atitle=A+phase+I+vaccine+trial+with+peptides+reflecting+ras+oncogene+mutations+of+solid+tumors.&rft.au=Khleif%2C+S+N%3BAbrams%2C+S+I%3BHamilton%2C+J+M%3BBergmann-Leitner%2C+E%3BChen%2C+A%3BBastian%2C+A%3BBernstein%2C+S%3BChung%2C+Y%3BAllegra%2C+C+J%3BSchlom%2C+J&rft.aulast=Khleif&rft.aufirst=S&rft.date=1999-03-01&rft.volume=22&rft.issue=2&rft.spage=155&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunotherapy+%28Hagerstown%2C+Md.+%3A+1997%29&rft.issn=15249557&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-13 N1 - Date created - 1999-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism. AN - 69646999; 10088048 AB - The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc). Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Alc randomly selected from a Finnish alcoholic population in which an association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in 1 OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Alc, or suicidality. These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated. JF - Biological psychiatry AU - Han, L AU - Nielsen, D A AU - Rosenthal, N E AU - Jefferson, K AU - Kaye, W AU - Murphy, D AU - Altemus, M AU - Humphries, J AU - Cassano, G AU - Rotondo, A AU - Virkkunen, M AU - Linnoila, M AU - Goldman, D AD - NIAAA/Lab of Neurogenetics, National Institutes of Health, Rockville, Maryland 20851, USA. Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 615 EP - 619 VL - 45 IS - 5 SN - 0006-3223, 0006-3223 KW - Tryptophan Hydroxylase KW - EC 1.14.16.4 KW - Index Medicus KW - Genotype KW - Humans KW - Tryptophan Hydroxylase -- genetics KW - Obsessive-Compulsive Disorder -- genetics KW - Anorexia Nervosa -- genetics KW - Seasonal Affective Disorder -- genetics KW - Genetic Variation -- genetics KW - Alcoholism -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69646999?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=No+coding+variant+of+the+tryptophan+hydroxylase+gene+detected+in+seasonal+affective+disorder%2C+obsessive-compulsive+disorder%2C+anorexia+nervosa%2C+and+alcoholism.&rft.au=Han%2C+L%3BNielsen%2C+D+A%3BRosenthal%2C+N+E%3BJefferson%2C+K%3BKaye%2C+W%3BMurphy%2C+D%3BAltemus%2C+M%3BHumphries%2C+J%3BCassano%2C+G%3BRotondo%2C+A%3BVirkkunen%2C+M%3BLinnoila%2C+M%3BGoldman%2C+D&rft.aulast=Han&rft.aufirst=L&rft.date=1999-03-01&rft.volume=45&rft.issue=5&rft.spage=615&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-10 N1 - Date created - 1999-08-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Photophysical studies on antimalarial drugs. AN - 69645895; 10089818 AB - Most drugs used in the treatment of malaria produce phototoxic side effects in both the skin and the eye. Cutaneous and ocular effects that may be caused by light include changes in skin pigmentation, corneal opacity, cataract formation and other visual disturbances including irreversible retinal damage (retinopathy) leading to blindness. The mechanism for these reactions in humans is unknown. We irradiated a number of antimalarial drugs (amodiaquine, chloroquine, hydroxychloroquine, mefloquine, primaquine and quinacrine) with light (lambda > 300 nm) and conducted electron paramagnetic resonance (EPR) and laser flash photolysis studies to determine the possible active intermediates produced. Each antimalarial drug produced at least one EPR adduct with the spin-trap 5,5-dimethyl-1-pyrroline N-oxide in benzene: superoxide/hydroperoxyl adducts (chloroquine, mefloquine, quinacrine, amodiaquine and quinine), carbon-centered radical adducts (all but primaquine), or a nitrogen-centered radical adduct only (primaquine). In ethanol all drugs except primaquine produced some superoxide/hydroperoxyl adduct, with quinine, quinacrine, and hydroxychloroquine also producing the ethoxyl adduct. As detected with flash photolysis and steady-state techniques, mefloquine, quinine, amodiquine and a photoproduct of quinacrine produced singlet oxygen ([symbol: see text]delta = 0.38; [symbol: see text]delta = 0.36; [symbol: see text]delta = 0.011; [symbol: see text]delta = 0.013 in D2O, pD7), but only primaquine quenched singlet oxygen efficiently (2.6 x 10(8) M-1 s-1 in D2O, pD7). Because malaria is a disease most prevalent in regions of high light intensity, protective measures (clothing, sunblock, sunglasses or eye wraps) should be recommended when administering antimalarial drugs. JF - Photochemistry and photobiology AU - Motten, A G AU - Martínez, L J AU - Holt, N AU - Sik, R H AU - Reszka, K AU - Chignell, C F AU - Tonnesen, H H AU - Roberts, J E AD - Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 282 EP - 287 VL - 69 IS - 3 SN - 0031-8655, 0031-8655 KW - Antimalarials KW - 0 KW - Free Radicals KW - Singlet Oxygen KW - 17778-80-2 KW - Oxygen KW - S88TT14065 KW - Index Medicus KW - Photosensitivity Disorders -- etiology KW - Photochemistry KW - Malaria -- drug therapy KW - Humans KW - Electron Spin Resonance Spectroscopy KW - Dermatitis, Phototoxic -- etiology KW - Light KW - Free Radicals -- radiation effects KW - Oxygen -- radiation effects KW - Eye Injuries -- etiology KW - Antimalarials -- chemistry KW - Antimalarials -- adverse effects KW - Antimalarials -- radiation effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69645895?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Photochemistry+and+photobiology&rft.atitle=Photophysical+studies+on+antimalarial+drugs.&rft.au=Motten%2C+A+G%3BMart%C3%ADnez%2C+L+J%3BHolt%2C+N%3BSik%2C+R+H%3BReszka%2C+K%3BChignell%2C+C+F%3BTonnesen%2C+H+H%3BRoberts%2C+J+E&rft.aulast=Motten&rft.aufirst=A&rft.date=1999-03-01&rft.volume=69&rft.issue=3&rft.spage=282&rft.isbn=&rft.btitle=&rft.title=Photochemistry+and+photobiology&rft.issn=00318655&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-30 N1 - Date created - 1999-04-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The mechanism of sugar phosphate isomerization by glucosamine 6-phosphate synthase. AN - 69643695; 10091662 AB - Glucosamine 6-phosphate synthase converts fructose-6P into glucosamine-6P or glucose-6P depending on the presence or absence of glutamine. The isomerase activity is associated with a 40-kDa C-terminal domain, which has already been characterized crystallographically. Now the three-dimensional structures of the complexes with the reaction product glucose-6P and with the transition state analog 2-amino-2-deoxyglucitol-6P have been determined. Glucose-6P binds in a cyclic form whereas 2-amino-2-deoxyglucitol-6P is in an extended conformation. The information on ligand-protein interactions observed in the crystal structures together with the isotope exchange and site-directed mutagenesis data allow us to propose a mechanism of the isomerase activity of glucosamine-6P synthase. The sugar phosphate isomerization involves a ring opening step catalyzed by His504 and an enolization step with Glu488 catalyzing the hydrogen transfer from C1 to C2 of the substrate. The enediol intermediate is stabilized by a helix dipole and the epsilon-amino group of Lys603. Lys485 may play a role in deprotonating the hydroxyl O1 of the intermediate. JF - Protein science : a publication of the Protein Society AU - Teplyakov, A AU - Obmolova, G AU - Badet-Denisot, M A AU - Badet, B AD - Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. alext@gm-mv.niddk.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 596 EP - 602 VL - 8 IS - 3 SN - 0961-8368, 0961-8368 KW - Glucose-6-Phosphate KW - 56-73-5 KW - Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) KW - EC 2.6.1.16 KW - Isomerases KW - EC 5.- KW - Index Medicus KW - Molecular Structure KW - Models, Molecular KW - Isomerism KW - Isomerases -- chemistry KW - Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) -- chemistry KW - Glucose-6-Phosphate -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69643695?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=The+mechanism+of+sugar+phosphate+isomerization+by+glucosamine+6-phosphate+synthase.&rft.au=Teplyakov%2C+A%3BObmolova%2C+G%3BBadet-Denisot%2C+M+A%3BBadet%2C+B&rft.aulast=Teplyakov&rft.aufirst=A&rft.date=1999-03-01&rft.volume=8&rft.issue=3&rft.spage=596&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - 1MOS; PDB; 1MOQ; 1MOR N1 - SuppNotes - Cited By: Biochim Biophys Acta. 1989 Oct 5;998(2):118-25 [2790058] Biochemistry. 1988 Aug 9;27(16):5948-60 [2847777] Nature. 1991 Mar 14;350(6314):121-4 [2005961] Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 [2025413] J Biol Chem. 1991 Jun 5;266(16):10148-54 [2037571] Arch Biochem Biophys. 1991 Jul;288(1):225-30 [1898018] Eur J Biochem. 1991 Oct 1;201(1):175-82 [1915361] Adv Enzymol Relat Areas Mol Biol. 1993;66:203-309 [8430515] Biochemistry. 1994 May 10;33(18):5469-80 [8180169] J Mol Biol. 1994 Oct 7;242(5):703-5 [7932726] Structure. 1995 Dec 15;3(12):1323-32 [8747459] Structure. 1996 Jul 15;4(7):801-10 [8805567] Protein Eng. 1995 Dec;8(12):1189-95 [8869631] Adv Enzymol Relat Areas Mol Biol. 1998;72:87-144 [9559052] Cell Mol Life Sci. 1998 Mar;54(3):205-22 [9575335] Structure. 1998 Aug 15;6(8):1047-55 [9739095] Proc Natl Acad Sci U S A. 1990 Feb;87(4):1362-6 [2304904] Adv Enzymol Relat Areas Mol Biol. 1975;43:491-517 [1106126] Biochemistry. 1987 Apr 7;26(7):1940-8 [3297136] Biochemistry. 1990 May 1;29(17):4099-108 [2361134] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. AN - 69637659; 10085337 AB - Hyperalgesic and nociceptor sensitizing effects mediated by the beta-adrenergic receptor were evaluated in the rat. Intradermal injection of epinephrine, the major endogenous ligand for the beta-adrenergic receptor, into the dorsum of the hindpaw of the rat produced a dose-dependent mechanical hyperalgesia, quantified by the Randall-Selitto paw-withdrawal test. Epinephrine-induced hyperalgesia was attenuated significantly by intradermal pretreatment with propranolol, a beta-adrenergic receptor antagonist, but not by phentolamine, an alpha-adrenergic receptor antagonist. Epinephrine-induced hyperalgesia developed rapidly; it was statistically significant by 2 min after injection, reached a maximum effect within 5 min, and lasted 2 h. Injection of a more beta-adrenergic receptor-selective agonist, isoproterenol, also produced dose-dependent hyperalgesia, which was attenuated by propranolol but not phentolamine. Epinephrine-induced hyperalgesia was not affected by indomethacin, an inhibitor of cyclo-oxygenase, or by surgical sympathectomy. It was attenuated significantly by inhibitors of the adenosine 3',5'-cyclic monophosphate signaling pathway (the adenylyl cyclase inhibitor, SQ 22536, and the protein kinase A inhibitors, Rp-adenosine 3',5'-cyclic monophosphate and WIPTIDE), inhibitors of the protein kinase C signaling pathway (chelerythrine and bisindolylmaleimide) and a mu-opioid receptor agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Consistent with the hypothesis that epinephrine produces hyperalgesia by a direct action on primary afferent nociceptors, it was found to sensitize small-diameter dorsal root ganglion neurons in culture, i. e., to produce an increase in number of spikes and a decrease in latency to firing during a ramped depolarizing stimulus. These effects were blocked by propranolol. Furthermore epinephrine, like several other direct-acting hyperalgesic agents, caused a potentiation of tetrodotoxin-resistant sodium current, an effect that was abolished by Rp-adenosine 3',5'-cyclic monophosphate and significantly attenuated by bisindolylmaleimide. Isoproterenol also potentiated tetrodotoxin-resistant sodium current. In conclusion, epinephrine produces cutaneous mechanical hyperalgesia and sensitizes cultured dorsal root ganglion neurons in the absence of nerve injury via an action at a beta-adrenergic receptor. These effects of epinephrine are mediated by both the protein kinase A and protein kinase C second-messenger pathways. JF - Journal of neurophysiology AU - Khasar, S G AU - McCarter, G AU - Levine, J D AD - Department of Medicine, Division of Neuroscience and Biomedical Sciences Program, National Institutes of Health Pain Center (UCSF), University of California, San Francisco, California 94143-0440, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1104 EP - 1112 VL - 81 IS - 3 SN - 0022-3077, 0022-3077 KW - Receptors, Adrenergic, beta KW - 0 KW - Sodium Channels KW - Tetrodotoxin KW - 4368-28-9 KW - Epinephrine KW - YKH834O4BH KW - Index Medicus KW - Space life sciences KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Analysis of Variance KW - Patch-Clamp Techniques KW - Second Messenger Systems -- physiology KW - Cells, Cultured KW - Stress, Mechanical KW - Drug Resistance KW - Tetrodotoxin -- pharmacology KW - Sodium Channels -- drug effects KW - Male KW - Ganglia, Spinal -- cytology KW - Epinephrine -- pharmacology KW - Receptors, Adrenergic, beta -- physiology KW - Ganglia, Spinal -- drug effects KW - Hyperalgesia -- chemically induced KW - Nociceptors -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69637659?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurophysiology&rft.atitle=Epinephrine+produces+a+beta-adrenergic+receptor-mediated+mechanical+hyperalgesia+and+in+vitro+sensitization+of+rat+nociceptors.&rft.au=Khasar%2C+S+G%3BMcCarter%2C+G%3BLevine%2C+J+D&rft.aulast=Khasar&rft.aufirst=S&rft.date=1999-03-01&rft.volume=81&rft.issue=3&rft.spage=1104&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurophysiology&rft.issn=00223077&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Lithium as a potential adjuvant to 131I therapy of metastatic, well differentiated thyroid carcinoma. AN - 69634354; 10084570 AB - As lithium inhibits the release of iodine from the thyroid but does not change iodine uptake, it may potentiate 131I therapy of thyroid cancer. The effects of lithium on the accumulation and retention of 131I in metastatic lesions and thyroid remnants were evaluated in 15 patients with differentiated thyroid carcinoma. Two 131I turnover studies were performed while the patients were hypothyroid. One was performed while the patient received lithium; the second served as a control study. From a series of gamma-camera images, it was found that lithium increased 131I retention in 24 of 31 metastatic lesions and in 6 of 7 thyroid remnants. A comparison of 131I retention during lithium with that during the control period showed that the mean increase in the biological or retention half-life was 50% in tumors and 90% in remnants. This increase occurred in at least 1 lesion in each patient and was proportionally greater in lesions with poor 131I retention. When the control biological half life was less than 3 days, lithium prolonged the effective half-life, which combines both biological turnover and isotope decay, in responding metastases by more than 50%. More 131I also accumulated during lithium therapy, probably as a consequence of its effect on iodine release. The increase in the accumulated 131I and the lengthening of the effective half-life combined to increase the estimated 131I radiation dose in metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest that lithium may be a useful adjuvant for 131I therapy of thyroid cancer, augmenting both the accumulation and retention of 131I in lesions. JF - The Journal of clinical endocrinology and metabolism AU - Koong, S S AU - Reynolds, J C AU - Movius, E G AU - Keenan, A M AU - Ain, K B AU - Lakshmanan, M C AU - Robbins, J AD - Nuclear Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 912 EP - 916 VL - 84 IS - 3 SN - 0021-972X, 0021-972X KW - Iodine Radioisotopes KW - 0 KW - Lithium KW - 9FN79X2M3F KW - Abridged Index Medicus KW - Index Medicus KW - Radiation Dosage KW - Half-Life KW - Combined Modality Therapy KW - Humans KW - Adult KW - Aged KW - Middle Aged KW - Male KW - Female KW - Iodine Radioisotopes -- therapeutic use KW - Carcinoma -- secondary KW - Carcinoma -- pathology KW - Carcinoma -- radiotherapy KW - Carcinoma -- drug therapy KW - Thyroid Neoplasms -- secondary KW - Thyroid Neoplasms -- drug therapy KW - Lithium -- therapeutic use KW - Thyroid Neoplasms -- pathology KW - Thyroid Neoplasms -- radiotherapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69634354?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+clinical+endocrinology+and+metabolism&rft.atitle=Lithium+as+a+potential+adjuvant+to+131I+therapy+of+metastatic%2C+well+differentiated+thyroid+carcinoma.&rft.au=Koong%2C+S+S%3BReynolds%2C+J+C%3BMovius%2C+E+G%3BKeenan%2C+A+M%3BAin%2C+K+B%3BLakshmanan%2C+M+C%3BRobbins%2C+J&rft.aulast=Koong&rft.aufirst=S&rft.date=1999-03-01&rft.volume=84&rft.issue=3&rft.spage=912&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+clinical+endocrinology+and+metabolism&rft.issn=0021972X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Weaver cerebellar granule neurons show altered expression of NMDA receptor subunits both in vivo and in vitro. AN - 69628388; 10084680 AB - Biochemical, immunocytochemical, and molecular biological techniques were used to investigate the expression of N-methyl-D-aspartate (NMDA) receptor subunits in migration-deficient weaver mouse cerebellum in vivo and in primary cultures of the vermal weaver granule neurons with or without a rescue by verapamil. We found that both NMDAR1(zeta1) message and protein were expressed by the weaver granule neurons in situ. Immunocytochemical and biochemical analyses indicated that granule neurons of the weaver cerebellum expressed R1(zeta1) and R2A(epsilon1) subunits but showed little expression of the R2B(epsilon2) subunit. In weaver cerebellum, the R2B(epsilon2) subunit was primarily expressed in nerve fibers of the internal granule cell layer and white matter. Reverse-transcriptase-polymerase chain reaction followed by sequence analysis of the R1(zeta1) subunit indicated that the zeta1 subunit amplicons of both normal and weaver cerebella were identical, and that splice variants with exon 22 (1-2) and with or without exon 5 (a/b) or exon 21 (1-4) were detectable. The R2A(epsilon1), and R2B(epsilon2) subunits of the normal and weaver mouse cerebellum revealed no primary structural differences between the normal and weaver NMDA receptor subunits or the cloned mouse NMDA receptor subunits. In vermal cultures, normal granule neurons expressed all three NMDA receptor subunits (zeta1, epsilon1, and epsilon2), whereas the weaver neurons failed to express the epsilon2 subunit. Rescue of the weaver neurons by verapamil induced expression of the epsilon2 protein along the granule neuronal surfaces. The present results suggest that lack of the epsilon2 subunit in the weaver cerebellum may relate to the lack of functional NMDA receptors and/or to the migratory failure of the weaver granule neurons. Our data further suggest that NMDA receptor-mediated neurotoxicity is an unlikely mediator of neuronal death of the weaver granule neurons. In fact, down-regulation of the NMDA receptor expression and function may be a protective measure of the weaver granule neurons to reduce calcium entry via these receptors. JF - Journal of neurobiology AU - Liesi, P AU - Stewart, R R AU - Akinshola, B E AU - Wright, J M AD - Laboratory of Molecular and Cellular Neurobiology, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 441 EP - 454 VL - 38 IS - 4 SN - 0022-3034, 0022-3034 KW - DNA Primers KW - 0 KW - NMDA receptor A1 KW - Receptors, N-Methyl-D-Aspartate KW - Verapamil KW - CJ0O37KU29 KW - Index Medicus KW - Animals KW - Cell Survival -- drug effects KW - Cells, Cultured KW - In Vitro Techniques KW - Mice, Neurologic Mutants KW - Mice KW - Verapamil -- pharmacology KW - Reverse Transcriptase Polymerase Chain Reaction KW - Cerebellum -- cytology KW - Neurons -- metabolism KW - Neurons -- drug effects KW - Neurons -- cytology KW - Receptors, N-Methyl-D-Aspartate -- genetics KW - Cerebellum -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69628388?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neurobiology&rft.atitle=Weaver+cerebellar+granule+neurons+show+altered+expression+of+NMDA+receptor+subunits+both+in+vivo+and+in+vitro.&rft.au=Liesi%2C+P%3BStewart%2C+R+R%3BAkinshola%2C+B+E%3BWright%2C+J+M&rft.aulast=Liesi&rft.aufirst=P&rft.date=1999-03-01&rft.volume=38&rft.issue=4&rft.spage=441&rft.isbn=&rft.btitle=&rft.title=Journal+of+neurobiology&rft.issn=00223034&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-11 N1 - Date created - 1999-05-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression. AN - 69628162; 10082085 AB - We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h-APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We were able to infect PC12 cells with very high efficiency because approximately 90% of the cells were cytochemically positive for beta-galactosidase activity when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells infected with adenovirus containing h-APP cDNA showed high-level transcription and expression of h-APP as measured by reverse transcriptase-polymerase chain reaction and Western immunoblot analyses, respectively. Intracellular and extracellular levels of h-APP were elevated approximately 17-and 24-fold in cultures infected with recombinant adenovirus containing wild-type mutant and 13- and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures infected with antisense h-APP or null adenovirus. H-APP levels were maximal 3 days after infection. Overexpression of V642F mutant h-APP in PC12 cells and hippocampal neurons resulted in about a twofold increase in death compared with overexpression of wild-type h-APP. These results demonstrate the usefulness of recombinant adenoviral mediated gene transfer in cell culture studies and suggest that overexpression of a familial Alzheimer's disease mutant APP may be toxic to neuronal cells. JF - Journal of neuroscience research AU - Luo, J J AU - Wallace, W AU - Riccioni, T AU - Ingram, D K AU - Roth, G S AU - Kusiak, J W AD - Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, Maryland 21224, USA. luoj@vax.grc.nia.nih.gov Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 629 EP - 642 VL - 55 IS - 5 SN - 0360-4012, 0360-4012 KW - Amyloid beta-Protein Precursor KW - 0 KW - RNA, Messenger KW - Recombinant Proteins KW - beta-Galactosidase KW - EC 3.2.1.23 KW - Index Medicus KW - Animals KW - Recombinant Proteins -- secretion KW - Cell Count KW - Gene Transfer Techniques KW - Recombinant Proteins -- biosynthesis KW - Gene Expression KW - Rats KW - Blotting, Western KW - Rats, Sprague-Dawley KW - beta-Galactosidase -- metabolism KW - RNA, Messenger -- metabolism KW - Recombinant Proteins -- metabolism KW - Cells, Cultured KW - Time Factors KW - Mutation KW - PC12 Cells KW - Alzheimer Disease -- genetics KW - Adenoviridae -- growth & development KW - Neurons -- cytology KW - Hippocampus -- cytology KW - Amyloid beta-Protein Precursor -- secretion KW - Cell Death -- genetics KW - Amyloid beta-Protein Precursor -- metabolism KW - Neurons -- secretion KW - Amyloid beta-Protein Precursor -- genetics KW - Adenoviridae -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69628162?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+neuroscience+research&rft.atitle=Death+of+PC12+cells+and+hippocampal+neurons+induced+by+adenoviral-mediated+FAD+human+amyloid+precursor+protein+gene+expression.&rft.au=Luo%2C+J+J%3BWallace%2C+W%3BRiccioni%2C+T%3BIngram%2C+D+K%3BRoth%2C+G+S%3BKusiak%2C+J+W&rft.aulast=Luo&rft.aufirst=J&rft.date=1999-03-01&rft.volume=55&rft.issue=5&rft.spage=629&rft.isbn=&rft.btitle=&rft.title=Journal+of+neuroscience+research&rft.issn=03604012&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-24 N1 - Date created - 1999-05-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients. AN - 69616348; 10049281 AB - The effects of multiple opportunistic infection medications on stavudine pharmacokinetics were evaluated. Ten patients with CD4 counts of less than 200 cells/mm3 received stavudine (40 mg twice daily) in combination with one to three other drugs used to treat opportunistic infections. Serial blood samples for stavudine concentrations were collected after 1 week of therapy on each regimen and assayed for stavudine by using a validated high-pressure liquid chromatography method. Although the maximum concentration of drug in serum was significantly decreased when the drug was given in combination with three opportunistic infection medications, the area under the concentration-time curve did not significantly differ across various treatment regimens. Stavudine exposure was not significantly altered by multiple concomitant medications. Side effects were minor throughout the 3-month study period. The tolerability of stavudine, combined with its lack of drug interactions, makes it an attractive agent for use as part of a combination regimen. JF - Antimicrobial agents and chemotherapy AU - Piscitelli, S C AU - Kelly, G AU - Walker, R E AU - Kovacs, J AU - Falloon, J AU - Davey, R T AU - Raje, S AU - Masur, H AU - Polis, M A AD - Department of Pharmacy, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1196, USA. spisc@nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 647 EP - 650 VL - 43 IS - 3 SN - 0066-4804, 0066-4804 KW - Anti-HIV Agents KW - 0 KW - Anti-Infective Agents KW - Stavudine KW - BO9LE4QFZF KW - Index Medicus KW - AIDS/HIV KW - Drug Interactions KW - Area Under Curve KW - Patient Compliance KW - Humans KW - Adult KW - Male KW - Female KW - AIDS-Related Opportunistic Infections -- drug therapy KW - Anti-Infective Agents -- therapeutic use KW - Anti-HIV Agents -- pharmacokinetics KW - Anti-Infective Agents -- adverse effects KW - Anti-HIV Agents -- therapeutic use KW - Stavudine -- therapeutic use KW - HIV Infections -- drug therapy KW - Anti-HIV Agents -- adverse effects KW - Stavudine -- adverse effects KW - Anti-Infective Agents -- pharmacology KW - Stavudine -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69616348?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antimicrobial+agents+and+chemotherapy&rft.atitle=A+multiple+drug+interaction+study+of+stavudine+with+agents+for+opportunistic+infections+in+human+immunodeficiency+virus-infected+patients.&rft.au=Piscitelli%2C+S+C%3BKelly%2C+G%3BWalker%2C+R+E%3BKovacs%2C+J%3BFalloon%2C+J%3BDavey%2C+R+T%3BRaje%2C+S%3BMasur%2C+H%3BPolis%2C+M+A&rft.aulast=Piscitelli&rft.aufirst=S&rft.date=1999-03-01&rft.volume=43&rft.issue=3&rft.spage=647&rft.isbn=&rft.btitle=&rft.title=Antimicrobial+agents+and+chemotherapy&rft.issn=00664804&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-22 N1 - Date created - 1999-06-22 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Clin Pharmacokinet. 1997 Oct;33(4):276-84 [9342503] J Infect Dis. 1997 Nov;176(5):1156-60 [9359713] Antimicrob Agents Chemother. 1993 Sep;37(9):1816-25 [8239589] Br J Clin Pharmacol. 1994 Nov;38(5):405-10 [7893580] Gastroenterol Clin North Am. 1995 Jun;24(2):413-34 [7642250] Clin Infect Dis. 1996 Oct;23(4):685-93 [8909827] AIDS. 1997 Oct;11(12):1523-5 [9342078] Antimicrob Agents Chemother. 1997 Jun;41(6):1231-6 [9174176] Gastroenterol Clin North Am. 1997 Jun;26(2):259-90 [9187925] Ann Intern Med. 1997 Aug 15;127(4):289-93 [9265429] Antimicrob Agents Chemother. 1997 Aug;41(8):1709-14 [9257746] N Engl J Med. 1997 Sep 11;337(11):725-33 [9287227] Ann Intern Med. 1997 Mar 1;126(5):355-63 [9054279] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. AN - 69613216; 10071291 AB - The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Rosenberg, S A AU - Yang, J C AU - Schwartzentruber, D J AU - Hwu, P AU - Marincola, F M AU - Topalian, S L AU - Seipp, C A AU - Einhorn, J H AU - White, D E AU - Steinberg, S M AD - Surgery Branch and Department of Biostatistics and Data Management Section, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. steven_rosenberg@nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 968 EP - 975 VL - 17 IS - 3 SN - 0732-183X, 0732-183X KW - Interferon-alpha KW - 0 KW - Interleukin-2 KW - Recombinant Proteins KW - Tamoxifen KW - 094ZI81Y45 KW - interferon alfa-2b KW - 43K1W2T1M6 KW - Dacarbazine KW - 7GR28W0FJI KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Interleukin-2 -- administration & dosage KW - Interleukin-2 -- adverse effects KW - Interferon-alpha -- administration & dosage KW - Combined Modality Therapy KW - Humans KW - Aged KW - Tamoxifen -- administration & dosage KW - Cisplatin -- administration & dosage KW - Interferon-alpha -- adverse effects KW - Prospective Studies KW - Adult KW - Neoplasm Metastasis KW - Middle Aged KW - Dacarbazine -- administration & dosage KW - Adolescent KW - Male KW - Female KW - Remission Induction KW - Melanoma -- drug therapy KW - Antineoplastic Combined Chemotherapy Protocols -- adverse effects KW - Antineoplastic Combined Chemotherapy Protocols -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69613216?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Prospective+randomized+trial+of+the+treatment+of+patients+with+metastatic+melanoma+using+chemotherapy+with+cisplatin%2C+dacarbazine%2C+and+tamoxifen+alone+or+in+combination+with+interleukin-2+and+interferon+alfa-2b.&rft.au=Rosenberg%2C+S+A%3BYang%2C+J+C%3BSchwartzentruber%2C+D+J%3BHwu%2C+P%3BMarincola%2C+F+M%3BTopalian%2C+S+L%3BSeipp%2C+C+A%3BEinhorn%2C+J+H%3BWhite%2C+D+E%3BSteinberg%2C+S+M&rft.aulast=Rosenberg&rft.aufirst=S&rft.date=1999-03-01&rft.volume=17&rft.issue=3&rft.spage=968&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-16 N1 - Date created - 1999-03-16 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Results of the National Cooperative Inner-City Asthma Study (NCICAS) environmental intervention to reduce cockroach allergen exposure in inner-city homes. AN - 69612319; 10069886 AB - Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed. We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings. As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group. The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P <.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P <.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P <.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up. Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant. JF - The Journal of allergy and clinical immunology AU - Gergen, P J AU - Mortimer, K M AU - Eggleston, P A AU - Rosenstreich, D AU - Mitchell, H AU - Ownby, D AU - Kattan, M AU - Baker, D AU - Wright, E C AU - Slavin, R AU - Malveaux, F AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 501 EP - 506 VL - 103 IS - 3 Pt 1 SN - 0091-6749, 0091-6749 KW - Allergens KW - 0 KW - Antigens, Plant KW - Dust KW - Insect Proteins KW - allergen Bla g 1 KW - Abridged Index Medicus KW - Index Medicus KW - Cross-Sectional Studies KW - Animals KW - Humans KW - Environmental Exposure KW - Program Evaluation KW - Urban Population KW - United States -- epidemiology KW - Asthma -- epidemiology KW - Asthma -- etiology KW - Housing KW - Dust -- analysis KW - Insect Proteins -- adverse effects KW - Asthma -- prevention & control KW - Cockroaches -- immunology KW - Allergens -- adverse effects KW - Allergens -- analysis KW - Insect Proteins -- analysis KW - Insect Control UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69612319?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+allergy+and+clinical+immunology&rft.atitle=Results+of+the+National+Cooperative+Inner-City+Asthma+Study+%28NCICAS%29+environmental+intervention+to+reduce+cockroach+allergen+exposure+in+inner-city+homes.&rft.au=Gergen%2C+P+J%3BMortimer%2C+K+M%3BEggleston%2C+P+A%3BRosenstreich%2C+D%3BMitchell%2C+H%3BOwnby%2C+D%3BKattan%2C+M%3BBaker%2C+D%3BWright%2C+E+C%3BSlavin%2C+R%3BMalveaux%2C+F&rft.aulast=Gergen&rft.aufirst=P&rft.date=1999-03-01&rft.volume=103&rft.issue=3+Pt+1&rft.spage=501&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+allergy+and+clinical+immunology&rft.issn=00916749&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-02 N1 - Date created - 1999-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Oxidative modification of glutamine synthetase by 2,2'-azobis(2- amidinopropane) dihydrochloride. AN - 69602330; 10049507 AB - In the present study, we examined the pattern of protein modification elicited by alkylperoxyl radicals and alkylperoxides. To this end, we exposed glutamine synthetase (GS) and the peptide melittin to solutions containing 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which is known to decompose in aqueous, aerobic solutions to yield alkyl radicals and alkylperoxides. Under our conditions, pH 7.4, 37 degrees C, the AAPH-dependent formation of alkylhydroperoxide increased linearly with time and led to 40% inactivation of GS in 1 h and to complete inactivation in 4 h. Complete inactivation was associated with the loss of 2 of 16 histidine residues, 6 of 17 tyrosine residues, 5 of 16 methionine residues, and all of the tryptophan residues (2 residues) per subunit. Inactivation of GS was associated also with some protein fragmentation and the formation of some higher molecular weight aggregates. Exposure of GS to AAPH led also to the generation of protein carbonyl derivatives (0.34 mol/mol subunit) and to formation of a significant amount (0.038 mol/mol subunits) of quinoprotein derivatives. To investigate the mechanism of tryptophan modification, the 26-amino-acid peptide, melittin, which contains one tryptophan but no histidine, tyrosine, or methionine residues, was treated with AAPH. N-Formylkynurenine was identified as the major product of tryptophan oxidation in melittin. Copyright 1999 Academic Press. JF - Archives of biochemistry and biophysics AU - Ma, Y S AU - Chao, C C AU - Stadtman, E R AD - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland, 20892-0342, USA. Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 129 EP - 134 VL - 363 IS - 1 SN - 0003-9861, 0003-9861 KW - Amidines KW - 0 KW - Oxidants KW - Reactive Oxygen Species KW - N'-formylkynurenine KW - 1022-31-7 KW - Melitten KW - 20449-79-0 KW - Kynurenine KW - 343-65-7 KW - Tyrosine KW - 42HK56048U KW - Histidine KW - 4QD397987E KW - 2,2'-azobis(2-amidinopropane) KW - 7381JDR72F KW - Tryptophan KW - 8DUH1N11BX KW - Methionine KW - AE28F7PNPL KW - Glutamate-Ammonia Ligase KW - EC 6.3.1.2 KW - Index Medicus KW - Reactive Oxygen Species -- metabolism KW - Electrophoresis, Polyacrylamide Gel KW - Methionine -- metabolism KW - Tryptophan -- metabolism KW - Chromatography, High Pressure Liquid KW - Kynurenine -- analogs & derivatives KW - Molecular Weight KW - Oxidation-Reduction KW - Enzyme Activation -- drug effects KW - Kynurenine -- metabolism KW - Tyrosine -- metabolism KW - Time Factors KW - Histidine -- metabolism KW - Melitten -- metabolism KW - Amidines -- pharmacology KW - Glutamate-Ammonia Ligase -- metabolism KW - Oxidants -- pharmacology KW - Glutamate-Ammonia Ligase -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69602330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+biochemistry+and+biophysics&rft.atitle=Oxidative+modification+of+glutamine+synthetase+by+2%2C2%27-azobis%282-+amidinopropane%29+dihydrochloride.&rft.au=Ma%2C+Y+S%3BChao%2C+C+C%3BStadtman%2C+E+R&rft.aulast=Ma&rft.aufirst=Y&rft.date=1999-03-01&rft.volume=363&rft.issue=1&rft.spage=129&rft.isbn=&rft.btitle=&rft.title=Archives+of+biochemistry+and+biophysics&rft.issn=00039861&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-22 N1 - Date created - 1999-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements. AN - 69601432; 10036235 AB - The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling. Here we examined the relationship between ARF6 and Rac1, a Rho family GTPase, implicated in cortical actin rearrangements. Endogenous Rac1 colocalized with ARF6 at the plasma membrane and on the ARF6 recycling endosome in untransfected HeLa and primary human fibroblast cells. In transfected HeLa cells Rac1 and ARF6 also colocalized. Cells expressing wild-type ARF6 or Rac1 formed actin-containing surface protrusions and membrane ruffles, respectively, upon treatment with the G protein activator aluminum fluoride. Aluminum fluoride-treatment of cells transfected with equivalent amounts of plasmid resulted in enhanced membrane ruffling, with protrusions appearing as Rac expression was lowered. Co-expression of the dominant negative, GTP binding-defective ARF6 T27N mutant inhibited the aluminum fluoride-induced ruffling observed in cells expressing Rac1, and the constitutive ruffling observed in cells expressing the activated Rac1 Q61L mutant. In contrast, co-expression of the GTP-binding-defective, T17N mutant of either Rac1 or Cdc42 with ARF6 did not inhibit the aluminum fluoride-induced surface protrusions, nor did inactivation of Rho with C3-transferase. These observations suggest that ARF6, a non-Rho family GTPase, can, by itself, alter cortical actin and can influence the ability of Rac1 to form lamellipodia, in part, by regulating its trafficking to the plasma membrane. JF - Journal of cell science AU - Radhakrishna, H AU - Al-Awar, O AU - Khachikian, Z AU - Donaldson, J G AD - Laboratory of Cell Biology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 855 EP - 866 VL - 112 ( Pt 6) SN - 0021-9533, 0021-9533 KW - Actins KW - 0 KW - Carrier Proteins KW - Recombinant Proteins KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - ADP-Ribosylation Factors KW - EC 3.6.5.2 KW - rac GTP-Binding Proteins KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Animals KW - COS Cells KW - Transfection KW - Recombinant Proteins -- metabolism KW - HeLa Cells KW - Humans KW - CHO Cells KW - Models, Biological KW - Amino Acid Substitution KW - Cricetinae KW - Carrier Proteins -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Cell Membrane -- ultrastructure KW - Actins -- metabolism KW - Cell Membrane -- physiology KW - GTP-Binding Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69601432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+cell+science&rft.atitle=ARF6+requirement+for+Rac+ruffling+suggests+a+role+for+membrane+trafficking+in+cortical+actin+rearrangements.&rft.au=Radhakrishna%2C+H%3BAl-Awar%2C+O%3BKhachikian%2C+Z%3BDonaldson%2C+J+G&rft.aulast=Radhakrishna&rft.aufirst=H&rft.date=1999-03-01&rft.volume=112+%28+Pt+6%29&rft.issue=&rft.spage=855&rft.isbn=&rft.btitle=&rft.title=Journal+of+cell+science&rft.issn=00219533&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-04 N1 - Date created - 1999-05-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Suppression of replication of multidrug-resistant HIV type 1 variants by combinations of thymidylate synthase inhibitors with zidovudine or stavudine. AN - 69600742; 10051538 AB - The replication of recombinant multidrug-resistant HIV-1 clones modeled on clinically derived resistant HIV-1 strains from patients receiving long-term combination therapy with zidovudine (AZT) plus 2',3'-dideoxycytidine was found to regain sensitivity to AZT and stavudine (D4T) as a consequence of a pharmacologically induced decrease in de novo dTMP synthesis. The host-cell system used was phytohemagglutinin-stimulated peripheral blood mononuclear cells; dTMP and dTTP depletion were induced by single exposures to a low level of the thymidylate synthase inhibitor 5-fluorouracil (5-FU) or its deoxynucleoside, 2'-deoxy-5-fluorouridine. The host-cell response to the latter was biphasic: a very rapid decrease in the rate of de novo dTMP formation and, consequently, in intracellular dTTP pools, followed by slower recovery in both indices over 3 to 24 h. With the additional presence of AZT or D4T, however, replication of the multidrug-resistant HIV-1 strains remained inhibited, indicating dependence of HIV DNA chain termination by AZT-5'-monophosphate or 2',3'-didehydro-2', 3'-dideoxythymidine-5'-monophosphate in these resistant strains on simultaneous inhibition of host-cell de novo synthesis of thymidine nucleotides. No effect on viability of control (uninfected) phytohemagglutinin-stimulated/peripheral blood mononuclear cells was noted on 6-day exposures to 5-FU or 2'-deoxy-5-fluorouridine alone or in combination with AZT or D4T, even at drug levels severalfold higher than those used in the viral inhibition studies. These studies may provide useful information for the potential clinical use of AZT/5-FU or D4T/5-FU combinations for the prevention or reversal of multidrug resistance associated with long-term dideoxynucleoside combination therapy. JF - Molecular pharmacology AU - Gao, W Y AU - Johns, D G AU - Tanaka, M AU - Mitsuya, H AD - Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 535 EP - 540 VL - 55 IS - 3 SN - 0026-895X, 0026-895X KW - Anti-HIV Agents KW - 0 KW - Antimetabolites KW - Reverse Transcriptase Inhibitors KW - Thymine Nucleotides KW - Floxuridine KW - 039LU44I5M KW - Zidovudine KW - 4B9XT59T7S KW - Stavudine KW - BO9LE4QFZF KW - Thymidylate Synthase KW - EC 2.1.1.45 KW - thymidine 5'-triphosphate KW - QOP4K539MU KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - AIDS/HIV KW - Antimetabolites -- pharmacology KW - Drug Interactions KW - Floxuridine -- pharmacology KW - Thymine Nucleotides -- metabolism KW - Virus Replication -- drug effects KW - Humans KW - Drug Resistance, Microbial KW - Fluorouracil -- pharmacology KW - Mutation KW - Drug Resistance, Multiple KW - Thymidylate Synthase -- antagonists & inhibitors KW - Reverse Transcriptase Inhibitors -- pharmacology KW - HIV-1 -- isolation & purification KW - Anti-HIV Agents -- pharmacology KW - Zidovudine -- pharmacology KW - Stavudine -- pharmacology KW - HIV-1 -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69600742?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+pharmacology&rft.atitle=Suppression+of+replication+of+multidrug-resistant+HIV+type+1+variants+by+combinations+of+thymidylate+synthase+inhibitors+with+zidovudine+or+stavudine.&rft.au=Gao%2C+W+Y%3BJohns%2C+D+G%3BTanaka%2C+M%3BMitsuya%2C+H&rft.aulast=Gao&rft.aufirst=W&rft.date=1999-03-01&rft.volume=55&rft.issue=3&rft.spage=535&rft.isbn=&rft.btitle=&rft.title=Molecular+pharmacology&rft.issn=0026895X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prostaglandin-E2 counteracts interleukin-1beta-stimulated upregulation of platelet-derived growth factor alpha-receptor on rat pulmonary myofibroblasts. AN - 69596789; 10030841 AB - The platelet-derived growth factor (PDGF) alpha-receptor (PDGF-Ralpha) is upregulated during lung fibrogenesis, and induction of PDGF-Ralpha on cultured lung myofibroblasts by interleukin (IL)-1beta results in an increased mitogenic response to PDGF. Because IL-1beta stimulates prostaglandin (PG) E2 production, we investigated whether IL-1beta could upregulate PDGF-Ralpha via a PGE2-dependent mechanism. IL-1beta increased the production of PGE2 by rat lung myofibroblasts and the cyclooxygenase (COX) inhibitor indomethacin blocked IL-1beta-induced PGE2 production. However, indomethacin did not inhibit IL-1beta-stimulated upregulation of [125I]PDGF-AA binding sites, indicating that PDGF-Ralpha induction does not require PGE2 synthesis. Instead, PGE2 downregulated PDGF-Ralpha protein and messenger RNA expression, and counteracted the IL-1beta-stimulated increase in [125I]PDGF-AA binding. Pretreatment of cells with indomethacin or the COX-2 specific inhibitor NS-398 attenuated the suppressive effect of exogenous PGE2 on PDGF-Ralpha, indicating that endogenous PGE2 released by IL-1beta treatment also contributed to downregulation of PDGF-Ralpha. PDGF-Rbeta expression was not altered by IL-1beta or PGE2. Pretreatment of myofibroblasts with IL-lbeta increased PDGF-stimulated mitogenesis, and this effect was blocked by coincubation with PGE2. In contrast, PGE2 enhanced epidermal growth factor- or basic fibroblast growth factor-2-stimulated cell proliferation approximately 50%. Because IL-1beta upregulates both PGE2 production and PDGF-Ralpha expression, these data suggest that PGE2 functions in a negative feedback loop to limit expression of PDGF-Ralpha and suppress PDGF-stimulated myofibroblast proliferation. JF - American journal of respiratory cell and molecular biology AU - Boyle, J E AU - Lindroos, P M AU - Rice, A B AU - Zhang, L AU - Zeldin, D C AU - Bonner, J C AD - Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 433 EP - 440 VL - 20 IS - 3 SN - 1044-1549, 1044-1549 KW - Antineoplastic Agents KW - 0 KW - Interleukin-1 KW - Mitogens KW - Platelet-Derived Growth Factor KW - Protein Isoforms KW - RNA, Messenger KW - platelet-derived growth factor A KW - Receptor, Platelet-Derived Growth Factor alpha KW - EC 2.7.10.1 KW - Receptors, Platelet-Derived Growth Factor KW - Dinoprostone KW - K7Q1JQR04M KW - Index Medicus KW - Rats KW - Platelet-Derived Growth Factor -- metabolism KW - Animals KW - Rats, Sprague-Dawley KW - RNA, Messenger -- analysis KW - Up-Regulation KW - Drug Antagonism KW - Male KW - Fibroblasts KW - Interleukin-1 -- pharmacology KW - Dinoprostone -- pharmacology KW - Lung -- drug effects KW - Receptors, Platelet-Derived Growth Factor -- genetics KW - Lung -- metabolism KW - Receptors, Platelet-Derived Growth Factor -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69596789?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+respiratory+cell+and+molecular+biology&rft.atitle=Prostaglandin-E2+counteracts+interleukin-1beta-stimulated+upregulation+of+platelet-derived+growth+factor+alpha-receptor+on+rat+pulmonary+myofibroblasts.&rft.au=Boyle%2C+J+E%3BLindroos%2C+P+M%3BRice%2C+A+B%3BZhang%2C+L%3BZeldin%2C+D+C%3BBonner%2C+J+C&rft.aulast=Boyle&rft.aufirst=J&rft.date=1999-03-01&rft.volume=20&rft.issue=3&rft.spage=433&rft.isbn=&rft.btitle=&rft.title=American+journal+of+respiratory+cell+and+molecular+biology&rft.issn=10441549&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-02 N1 - Date created - 1999-04-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: comparisons with methamphetamine. AN - 69587394; 10027871 AB - Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psychostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depression. It has been described as a stimulant with an addiction liability and toxicity less than that of amphetamines. The present study undertook to evaluate the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduced potency (approximately 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of both methamphetamine and sydnocarb were dose-dependently blocked by the dopamine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade generally occurred at doses of the antagonists that did not depress locomotor activity when given alone. In mice trained to discriminate methamphetamine from saline, sydnocarb fully substituted for methamphetamine with a 9-fold lower potency. When substituted for methamphetamine under self-administration experiments in rats, 10-fold higher concentrations of sydnocarb maintained responding by its i.v. presentation. Sydnocarb engendered stereotypy in high doses with approximately a 2-fold lower potency than methamphetamine. However, sydnocarb was much less efficacious than methamphetamine in inducing stereotyped behavior. Both sydnocarb and methamphetamine increased dialysate levels of dopamine in mouse striatum; however, the potency and efficacy of sydnocarb was less than methamphetamine. The convulsive effects of cocaine were significantly enhanced by the coadministration of nontoxic doses of methamphetamine but not of sydnocarb. Taken together, the present findings indicate that sydnocarb has psychomotor stimulant effects that are shared by methamphetamine while demonstrating a reduced behavioral toxicity. JF - The Journal of pharmacology and experimental therapeutics AU - Witkin, J M AU - Savtchenko, N AU - Mashkovsky, M AU - Beekman, M AU - Munzar, P AU - Gasior, M AU - Goldberg, S R AU - Ungard, J T AU - Kim, J AU - Shippenberg, T AU - Chefer, V AD - Drug Development Group and Integrative Neuroscience Unit Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. jwitkin@intra.nida.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1298 EP - 1310 VL - 288 IS - 3 SN - 0022-3565, 0022-3565 KW - Benzazepines KW - 0 KW - Central Nervous System Stimulants KW - Dopamine Antagonists KW - Sydnones KW - ecopipam KW - 0X748O646K KW - Methamphetamine KW - 44RAL3456C KW - Haloperidol KW - J6292F8L3D KW - sidnocarb KW - UMT8MP2NDU KW - Dopamine KW - VTD58H1Z2X KW - Index Medicus KW - Discrimination Learning -- drug effects KW - Animals KW - Benzazepines -- pharmacology KW - Maze Learning -- drug effects KW - Dose-Response Relationship, Drug KW - Dopamine Antagonists -- pharmacology KW - Dopamine -- metabolism KW - Stereotyped Behavior -- drug effects KW - Brain -- metabolism KW - Mice KW - Self Administration KW - Psychomotor Performance -- drug effects KW - Haloperidol -- pharmacology KW - Motor Activity -- drug effects KW - Male KW - Sydnones -- administration & dosage KW - Methamphetamine -- administration & dosage KW - Central Nervous System Stimulants -- pharmacology KW - Sydnones -- toxicity KW - Methamphetamine -- pharmacology KW - Sydnones -- pharmacology KW - Methamphetamine -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69587394?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Behavioral%2C+toxic%2C+and+neurochemical+effects+of+sydnocarb%2C+a+novel+psychomotor+stimulant%3A+comparisons+with+methamphetamine.&rft.au=Witkin%2C+J+M%3BSavtchenko%2C+N%3BMashkovsky%2C+M%3BBeekman%2C+M%3BMunzar%2C+P%3BGasior%2C+M%3BGoldberg%2C+S+R%3BUngard%2C+J+T%3BKim%2C+J%3BShippenberg%2C+T%3BChefer%2C+V&rft.aulast=Witkin&rft.aufirst=J&rft.date=1999-03-01&rft.volume=288&rft.issue=3&rft.spage=1298&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-01 N1 - Date created - 1999-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness. AN - 69586381; 10022868 AB - Transcription factors of the interferon regulatory factor (IRF) family bind to the type I interferon (IFN)-responsive element (ISRE) and activate transcription from IFN-inducible genes. To identify cofactors that associate with IRF proteins, DNA affinity binding assays were performed with nuclear extracts prepared from tissue culture cells. The results demonstrated that the endogenous IRFs bound to the ISRE are complexed with the histone acetylases, PCAF, GCN5, and p300/CREB binding protein and that histone acetylase activities are accumulated on the IRF-ISRE complexes. By testing recombinant proteins, we show that PCAF directly binds to some but not all members of the IRF family through distinct domains of the two proteins. This interaction was functionally significant, since transfection of PCAF strongly enhanced IRF-1- and IRF-2-dependent promoter activities. Further studies showed that expression of PCAF and other histone acetylases was markedly induced in U937 cells upon phorbol ester treatment, which led to increased recruitment of PCAF to the IRF-ISRE complexes. Coinciding with the induction of histone acetylases, phorbol ester markedly enhanced IFN-alpha-stimulated gene expression in U937 cells. Supporting the role for PCAF in conferring IFN responsiveness, transfection of PCAF into U937 cells led to a large increase in IFN-alpha-inducible promoter activity. These results demonstrate that PCAF is a phorbol ester-inducible coactivator of the IRF proteins which contributes to the establishment of type I IFN responsiveness. JF - Molecular and cellular biology AU - Masumi, A AU - Wang, I M AU - Lefebvre, B AU - Yang, X J AU - Nakatani, Y AU - Ozato, K AD - Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1810 EP - 1820 VL - 19 IS - 3 SN - 0270-7306, 0270-7306 KW - Cell Cycle Proteins KW - 0 KW - DNA-Binding Proteins KW - IRF1 protein, human KW - IRF2 protein, human KW - Interferon Regulatory Factor-1 KW - Interferon Regulatory Factor-2 KW - Interferon Regulatory Factors KW - Interferon-alpha KW - Irf1 protein, mouse KW - Irf2 protein, mouse KW - Nuclear Proteins KW - Phosphoproteins KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Trans-Activators KW - Transcription Factors KW - interferon regulatory factor-4 KW - interferon regulatory factor-8 KW - Acetyltransferases KW - EC 2.3.1.- KW - CREB-Binding Protein KW - EC 2.3.1.48 KW - CREBBP protein, human KW - Crebbp protein, mouse KW - E1A-Associated p300 Protein KW - Ep300 protein, mouse KW - Gcn5l2 protein, mouse KW - Histone Acetyltransferases KW - KAT2A protein, human KW - p300-CBP Transcription Factors KW - p300-CBP-associated factor KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Trans-Activators -- metabolism KW - Animals KW - Spodoptera KW - Humans KW - Repressor Proteins -- metabolism KW - Gene Expression KW - Recombinant Fusion Proteins -- metabolism KW - Promoter Regions, Genetic KW - Trans-Activators -- genetics KW - Binding, Competitive KW - Recombinant Fusion Proteins -- genetics KW - Nuclear Proteins -- metabolism KW - Response Elements KW - Mice KW - Repressor Proteins -- genetics KW - Binding Sites KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Cell Line KW - U937 Cells KW - Interferon-alpha -- pharmacology KW - Phosphoproteins -- genetics KW - Acetyltransferases -- metabolism KW - DNA-Binding Proteins -- genetics KW - Phosphoproteins -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69586381?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+histone+acetylase+PCAF+is+a+phorbol-ester-inducible+coactivator+of+the+IRF+family+that+confers+enhanced+interferon+responsiveness.&rft.au=Masumi%2C+A%3BWang%2C+I+M%3BLefebvre%2C+B%3BYang%2C+X+J%3BNakatani%2C+Y%3BOzato%2C+K&rft.aulast=Masumi&rft.aufirst=A&rft.date=1999-03-01&rft.volume=19&rft.issue=3&rft.spage=1810&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1995 Sep 28;377(6547):362-5 [7566094] Biochimie. 1985 Oct-Nov;67(10-11):1103-10 [3907714] Semin Cell Biol. 1995 Aug;6(4):229-36 [8562915] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11657-61 [8524823] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):211-5 [8552607] Mol Cell Biol. 1996 Feb;16(2):593-602 [8552087] Cell. 1996 Mar 22;84(6):843-51 [8601308] Science. 1996 Apr 19;272(5260):408-11 [8602529] J Immunol. 1996 May 15;156(10):3711-20 [8621906] EMBO J. 1985 Sep;4(9):2249-56 [2416561] Cell. 1990 Oct 19;63(2):303-12 [2208287] J Interferon Res. 1992 Apr;12(2):87-94 [1315834] Nucleic Acids Res. 1992 May 25;20(10):2603 [1350857] Mol Cell Biol. 1992 Aug;12(8):3315-24 [1630447] Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7836-9 [1502203] Mol Cell Biol. 1993 Jan;13(1):588-99 [7678054] Mol Cell Biol. 1993 Jun;13(6):3245-54 [8497250] Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046-50 [8197182] Curr Opin Cell Biol. 1994 Apr;6(2):253-9 [8024817] J Biol Chem. 1995 Jun 2;270(22):13063-9 [7768900] Genes Dev. 1995 Jun 1;9(11):1377-87 [7797077] Cytokine Growth Factor Rev. 1997 Dec;8(4):293-312 [9620643] Genes Dev. 1998 Jun 1;12(11):1638-51 [9620851] Mol Cell. 1997 Dec;1(1):35-45 [9659901] Mol Cell. 1998 Jan;1(2):277-87 [9659924] Mol Cell Biol. 1996 Apr;16(4):1283-94 [8657101] Curr Opin Genet Dev. 1996 Apr;6(2):176-84 [8722174] Nature. 1996 Jul 25;382(6589):319-24 [8684459] Nature. 1996 Sep 5;383(6595):99-103 [8779723] Nature. 1996 Sep 19;383(6597):269-72 [8805705] Nature. 1996 Sep 26;383(6598):344-7 [8848048] Genes Dev. 1996 Sep 15;10(18):2335-47 [8824592] Cell. 1996 Oct 18;87(2):307-17 [8861914] Mol Cell Biol. 1996 Nov;16(11):6313-24 [8887661] Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12451-5 [8901602] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12845-50 [8917507] J Immunol. 1996 Dec 1;157(11):5145-54 [8943426] Cell. 1996 Nov 29;87(5):953-9 [8945521] Nature. 1996 Dec 19-26;384(6610):641-3 [8967953] Cell. 1996 Dec 27;87(7):1261-70 [8980232] Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15092-6 [8986769] EMBO J. 1997 Jan 15;16(2):406-16 [9029159] Genes Dev. 1997 Jul 1;11(13):1640-50 [9224714] Cell. 1997 Aug 8;90(3):569-80 [9267036] Mol Cell Biol. 1997 Sep;17(9):5033-43 [9271381] Genes Cells. 1997 May;2(5):291-302 [9280341] Curr Biol. 1997 Sep 1;7(9):689-92 [9285713] Cell. 1997 Aug 22;90(4):595-606 [9288740] Nature. 1997 Sep 11;389(6647):194-8 [9296499] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Mol Cell Biol. 1997 Oct;17(10):5748-57 [9315633] Blood. 1997 Nov 1;90(9):3430-7 [9345026] J Biol Chem. 1998 Jan 16;273(3):1430-4 [9430679] Science. 1998 Jan 30;279(5351):703-7 [9445475] EMBO J. 1998 Feb 16;17(4):1087-95 [9463386] Mol Cell Biol. 1998 Mar;18(3):1349-58 [9488450] Mol Cell Biol. 1998 Mar;18(3):1359-68 [9488451] Genes Dev. 1998 Mar 1;12(5):599-606 [9499396] J Immunol Methods. 1997 Dec 29;210(2):175-84 [9520300] Mol Cell Biol. 1998 May;18(5):2986-96 [9566918] J Cancer Res Clin Oncol. 1995;121(9-10):516-20 [7559730] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The 3'-->5' exonucleases of DNA polymerases delta and epsilon and the 5'-->3' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae. AN - 69585960; 10022887 AB - Replication fidelity is controlled by DNA polymerase proofreading and postreplication mismatch repair. We have genetically characterized the roles of the 5'-->3' Exo1 and the 3'-->5' DNA polymerase exonucleases in mismatch repair in the yeast Saccharomyces cerevisiae by using various genetic backgrounds and highly sensitive mutation detection systems that are based on long and short homonucleotide runs. Genetic interactions were examined among DNA polymerase epsilon (pol2-4) and delta (pol3-01) mutants defective in 3'-->5' proofreading exonuclease, mutants defective in the 5'-->3' exonuclease Exo1, and mismatch repair mutants (msh2, msh3, or msh6). These three exonucleases play an important role in mutation avoidance. Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3-01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes. JF - Molecular and cellular biology AU - Tran, H T AU - Gordenin, D A AU - Resnick, M A AD - Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 2000 EP - 2007 VL - 19 IS - 3 SN - 0270-7306, 0270-7306 KW - DNA, Fungal KW - 0 KW - DNA-Binding Proteins KW - Fungal Proteins KW - Saccharomyces cerevisiae Proteins KW - DNA Polymerase II KW - EC 2.7.7.- KW - DNA Polymerase III KW - Exodeoxyribonucleases KW - EC 3.1.- KW - exodeoxyribonuclease I KW - EC 3.1.11.1 KW - Exodeoxyribonuclease V KW - EC 3.1.11.5 KW - MSH2 protein, S cerevisiae KW - EC 3.6.1.3 KW - MutS Homolog 2 Protein KW - Index Medicus KW - Phenotype KW - Fungal Proteins -- metabolism KW - DNA Repair KW - DNA-Binding Proteins -- genetics KW - Fungal Proteins -- genetics KW - DNA Replication KW - Diploidy KW - DNA-Binding Proteins -- metabolism KW - Saccharomyces cerevisiae -- genetics KW - DNA Polymerase II -- metabolism KW - DNA Polymerase III -- genetics KW - Saccharomyces cerevisiae -- enzymology KW - Exodeoxyribonucleases -- genetics KW - DNA Polymerase II -- genetics KW - DNA Polymerase III -- metabolism KW - Exodeoxyribonucleases -- metabolism KW - Mutagenesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69585960?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+3%27--%26gt%3B5%27+exonucleases+of+DNA+polymerases+delta+and+epsilon+and+the+5%27--%26gt%3B3%27+exonuclease+Exo1+have+major+roles+in+postreplication+mutation+avoidance+in+Saccharomyces+cerevisiae.&rft.au=Tran%2C+H+T%3BGordenin%2C+D+A%3BResnick%2C+M+A&rft.aulast=Tran&rft.aufirst=H&rft.date=1999-03-01&rft.volume=19&rft.issue=3&rft.spage=2000&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: EMBO J. 1993 Apr;12(4):1467-73 [8385605] Yeast. 1991 Aug-Sep;7(6):609-15 [1767589] J Biol Chem. 1993 Jun 5;268(16):11838-44 [8505312] Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5613-7 [8516308] J Biol Chem. 1993 Nov 15;268(32):23762-5 [8226906] Mol Gen Genet. 1994 Feb;242(3):289-96 [8107676] Genes Dev. 1994 May 1;8(9):1087-105 [7926789] Science. 1995 Feb 24;267(5201):1166-9 [7855597] Yeast. 1994 Dec;10(13):1793-808 [7747518] Genetics. 1995 Mar;139(3):1175-88 [7768431] Science. 1995 Jul 14;269(5221):238-40 [7618086] Trends Biochem Sci. 1995 Aug;20(8):319-23 [7667891] Mol Cell Biol. 1995 Oct;15(10):5607-17 [7565712] Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10418-21 [7479796] Biochemistry. 1996 Jan 23;35(3):1046-53 [8547240] Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2856-61 [8610131] Annu Rev Biochem. 1996;65:101-33 [8811176] Genetics. 1996 Aug;143(4):1579-87 [8844147] Genetics. 1996 Mar;142(3):727-36 [8849883] Cell. 1996 Oct 4;87(1):65-73 [8858149] J Biol Chem. 1996 Nov 8;271(45):27987-90 [8910404] Mol Cell Biol. 1997 Feb;17(2):1027-36 [9001255] J Biol Chem. 1997 Apr 18;272(16):10917-21 [9099749] Mol Cell Biol. 1997 May;17(5):2764-73 [9111347] Mol Cell Biol. 1997 May;17(5):2844-50 [9111356] Mol Cell Biol. 1997 May;17(5):2851-8 [9111357] Mol Cell Biol. 1997 May;17(5):2859-65 [9111358] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7487-92 [9207118] Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9214-9 [9256462] Mol Cell Biol. 1997 Nov;17(11):6367-78 [9343398] Mol Cell Biol. 1998 May;18(5):2779-88 [9566897] Genetics. 1998 May;149(1):7-16 [9584082] Mol Gen Genet. 1984;197(2):345-6 [6394957] Proc Natl Acad Sci U S A. 1988 Nov;85(21):8126-30 [3054881] Science. 1989 Jul 14;245(4914):160-4 [2665076] J Biol Chem. 1991 Feb 25;266(6):3744-51 [1995629] J Biol Chem. 1991 Apr 5;266(10):6336-41 [2007586] EMBO J. 1991 Aug;10(8):2165-70 [1648480] Yeast. 1991 Apr;7(3):253-63 [1882550] Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9473-7 [1658784] J Biol Chem. 1993 Jun 5;268(16):11823-9 [8389365] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of p53 function and stability by phosphorylation. AN - 69585876; 10022862 AB - The p53 tumor suppressor protein can be phosphorylated at several sites within the N- and C-terminal domains, and several protein kinases have been shown to phosphorylate p53 in vitro. In this study, we examined the activity of p53 proteins with combined mutations at all of the reported N-terminal phosphorylation sites (p53N-term), all of the C-terminal phosphorylation sites (p53C-term), or all of the phosphorylation sites together (p53N/C-term). Each of these mutant proteins retained transcriptional transactivation functions, indicating that phosphorylation is not essential for this activity of p53, although a subtle contribution of the C-terminal phosphorylation sites to the activation of expression of the endogenous p21(Waf1/Cip1)-encoding gene was detected. Mutation of the phosphorylation sites to alanine did not affect the sensitivity of p53 to binding to or degradation by Mdm2, although alteration of residues 15 and 37 to aspartic acid, which could mimic phosphorylation, resulted in a slight resistance to Mdm2-mediated degradation, consistent with recent reports that phosphorylation at these sites inhibits the p53-Mdm2 interaction. However, expression of the phosphorylation site mutant proteins in both wild-type p53-expressing and p53-null lines showed that all of the mutant proteins retained the ability to be stabilized following DNA damage. This indicates that phosphorylation is not essential for DNA damage-induced stabilization of p53, although phosphorylation could clearly contribute to p53 stabilization under some conditions. JF - Molecular and cellular biology AU - Ashcroft, M AU - Kubbutat, M H AU - Vousden, K H AD - ABL Basic Research Program, NCI-FCRDC, Frederick, Maryland, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1751 EP - 1758 VL - 19 IS - 3 SN - 0270-7306, 0270-7306 KW - Tumor Suppressor Protein p53 KW - 0 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Tumor Cells, Cultured KW - Phosphorylation KW - Humans KW - Binding Sites KW - Tumor Suppressor Protein p53 -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69585876?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Regulation+of+p53+function+and+stability+by+phosphorylation.&rft.au=Ashcroft%2C+M%3BKubbutat%2C+M+H%3BVousden%2C+K+H&rft.aulast=Ashcroft&rft.aufirst=M&rft.date=1999-03-01&rft.volume=19&rft.issue=3&rft.spage=1751&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Eur J Biochem. 1986 Sep 15;159(3):529-34 [2428616] Life Sci. 1997;60(1):1-11 [8995526] EMBO J. 1992 Aug;11(8):3045-52 [1379175] Oncogene. 1996 Dec 19;13(12):2527-39 [9000127] Cell. 1997 Feb 7;88(3):323-31 [9039259] Nature. 1997 May 15;387(6630):296-9 [9153395] Nature. 1997 May 15;387(6630):299-303 [9153396] Cell. 1997 Aug 22;90(4):595-606 [9288740] Oncogene. 1997 Sep 4;15(10):1179-89 [9294611] Cell. 1997 Oct 31;91(3):325-34 [9363941] Curr Biol. 1997 Nov 1;7(11):860-9 [9382809] Genes Dev. 1997 Dec 15;11(24):3471-81 [9407038] Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2834-7 [9501176] Cell. 1998 Mar 20;92(6):713-23 [9529248] Cell Signal. 1998 Mar;10(3):159-66 [9607138] Nat Genet. 1998 Jun;19(2):175-8 [9620776] Mol Cell Biol. 1998 Jul;18(7):3692-8 [9632751] Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8292-7 [9653180] J Virol. 1998 Aug;72(8):6348-55 [9658074] Mol Med Today. 1998 Jun;4(6):250-6 [9679243] EMBO J. 1998 Sep 1;17(17):5001-14 [9724636] Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10541-6 [9724739] Genes Dev. 1998 Sep 1;12(17):2658-63 [9732264] Science. 1998 Sep 11;281(5383):1674-7 [9733514] Science. 1998 Sep 11;281(5383):1677-9 [9733515] Mol Cell Biol. 1998 Oct;18(10):5690-8 [9742086] Genes Dev. 1998 Sep 15;12(18):2831-41 [9744860] Oncogene. 1998 Aug 27;17(8):1045-52 [9747884] Cell. 1998 Oct 2;95(1):5-8 [9778240] Cell. 1992 Nov 27;71(5):875-86 [1423635] Nucleic Acids Res. 1992 Nov 11;20(21):5565-70 [1454521] Oncogene. 1993 Jun;8(6):1519-28 [8502477] Cell. 1993 Nov 19;75(4):817-25 [8242752] Oncogene. 1993 Dec;8(12):3411-6 [8247544] EMBO J. 1993 Dec 15;12(13):5057-64 [8262048] Oncogene. 1994 Sep;9(9):2707-16 [8058335] Oncogene. 1994 Nov;9(11):3249-57 [7936649] Semin Cancer Biol. 1994 Jun;5(3):203-10 [7948948] Cell. 1994 Dec 2;79(5):817-27 [8001119] Oncogene. 1995 Feb 16;10(4):789-93 [7862459] Oncogene. 1995 May 4;10(9):1709-15 [7753547] Cancer Res. 1995 Jun 1;55(11):2410-7 [7757994] EMBO J. 1996 Feb 15;15(4):827-38 [8631304] Oncogene. 1996 Feb 15;12(4):921-30 [8632915] EMBO J. 1996 Apr 1;15(7):1596-606 [8612583] Mol Cell Biol. 1996 Sep;16(9):4961-71 [8756655] Curr Opin Genet Dev. 1996 Feb;6(1):12-8 [8791489] J Biol Chem. 1996 Nov 15;271(46):29380-5 [8910602] J Immunol Methods. 1992 Jul 6;151(1-2):237-44 [1378473] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A new member of the Sin3 family of corepressors is essential for cell viability and required for retroelement propagation in fission yeast. AN - 69584134; 10022921 AB - Tf1 is a long terminal repeat (LTR)-containing retrotransposon that propagates within the fission yeast Schizosaccharomyces pombe. LTR-retrotransposons possess significant similarity to retroviruses and therefore serve as retrovirus models. To determine what features of the host cell are important for the proliferation of this class of retroelements, we screened for mutations in host genes that reduced the transposition activity of Tf1. We report here the isolation and characterization of pst1(+), a gene required for Tf1 transposition. The predicted amino acid sequence of Pst1p possessed high sequence homology with the Sin3 family of proteins, known for their interaction with histone deacetylases. However, unlike the SIN3 gene of Saccharomyces cerevisiae, pst1(+) is essential for cell viability. Immunofluorescence microscopy indicated that Pst1p was localized in the nucleus. Consistent with the critical role previously reported for Sin3 proteins in the histone acetylation process, we found that the growth of the strain with the pst1-1 allele was supersensitive to the specific histone deacetylase inhibitor trichostatin A. However, our analysis of strains with the pst1-1 mutation was unable to detect any changes in the acetylation of specific lysines of histones H3 and H4 as measured in bulk chromatin. Interestingly, the pst1-1 mutant strain produced wild-type levels of Tf1-encoded proteins and cDNA, indicating that the defect in transposition occurred after reverse transcription. The results of immunofluorescence microscopy showed that the nuclear localization of the Tf1 capsid protein was disrupted in the strain with the pst1-1 mutation, indicating an important role of pst1(+) in modulating the nuclear import of Tf1 virus-like particles. JF - Molecular and cellular biology AU - Dang, V D AU - Benedik, M J AU - Ekwall, K AU - Choi, J AU - Allshire, R C AU - Levin, H L AD - Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 2351 EP - 2365 VL - 19 IS - 3 SN - 0270-7306, 0270-7306 KW - Enzyme Inhibitors KW - 0 KW - Fungal Proteins KW - Hemagglutinins KW - Histone Deacetylase Inhibitors KW - Hydroxamic Acids KW - Repressor Proteins KW - Retroelements KW - SIN3 protein, S cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Schizosaccharomyces pombe Proteins KW - Transcription Factors KW - pst1 protein, S pombe KW - trichostatin A KW - 3X2S926L3Z KW - Histone Deacetylases KW - EC 3.5.1.98 KW - Index Medicus KW - Saccharomyces cerevisiae -- genetics KW - Molecular Sequence Data KW - Histone Deacetylases -- metabolism KW - Enzyme Inhibitors -- pharmacology KW - Amino Acid Sequence KW - Hydroxamic Acids -- pharmacology KW - Mutagenesis KW - Schizosaccharomyces -- genetics KW - Fungal Proteins -- metabolism KW - Transcription Factors -- metabolism KW - Repressor Proteins -- metabolism KW - Fungal Proteins -- genetics KW - Transcription Factors -- genetics KW - Repressor Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69584134?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=A+new+member+of+the+Sin3+family+of+corepressors+is+essential+for+cell+viability+and+required+for+retroelement+propagation+in+fission+yeast.&rft.au=Dang%2C+V+D%3BBenedik%2C+M+J%3BEkwall%2C+K%3BChoi%2C+J%3BAllshire%2C+R+C%3BLevin%2C+H+L&rft.aulast=Dang&rft.aufirst=V&rft.date=1999-03-01&rft.volume=19&rft.issue=3&rft.spage=2351&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Biol Chem. 1994 Oct 7;269(40):25031-41 [7929189] Genetics. 1994 Nov;138(3):587-95 [7851757] Genes Dev. 1995 Jan 15;9(2):218-33 [7851795] Science. 1995 Mar 10;267(5203):1488-91 [7878467] Cell. 1995 Mar 10;80(5):767-76 [7889570] Cell. 1995 Mar 10;80(5):777-86 [7889571] Yeast. 1994 Oct;10(10):1273-83 [7900416] Mol Cell Biol. 1995 Jun;15(6):3310-7 [7760826] Bioessays. 1995 May;17(5):423-30 [7786288] Science. 1995 Sep 8;269(5229):1429-31 [7660126] Cell. 1995 Nov 17;83(4):569-76 [7585960] Semin Cell Biol. 1995 Aug;6(4):229-36 [8562915] Genetics. 1990 Jun;125(2):313-20 [2199313] Mol Cell Biol. 1990 Nov;10(11):5927-36 [2233725] Mol Cell Biol. 1990 Dec;10(12):6791-8 [2174117] Methods Enzymol. 1991;194:795-823 [2005825] Proteins. 1991;9(3):180-90 [2006136] Trends Biochem Sci. 1991 May;16(5):173-7 [1882418] Cell. 1997 May 2;89(3):325-8 [9150131] Cell. 1997 May 2;89(3):349-56 [9150134] Cell. 1997 May 2;89(3):365-71 [9150136] Cell. 1997 May 2;89(3):373-80 [9150137] Science. 1997 Jul 4;277(5322):105-9 [9204892] Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7412-6 [9207105] Mol Cell Biol. 1997 Aug;17(8):4852-8 [9234741] Nature. 1997 Sep 25;389(6649):349-52 [9311776] Cell. 1997 Dec 26;91(7):1021-32 [9428524] J Virol. 1998 Feb;72(2):1324-33 [9445033] Mol Cell Biol. 1998 Feb;18(2):1105-14 [9448008] Cell Mol Life Sci. 1998 Jan;54(1):6-20 [9487383] Genes Dev. 1998 Mar 1;12(5):599-606 [9499396] Mol Cell Biol. 1996 Jan;16(1):338-46 [8524313] J Virol. 1996 Feb;70(2):1027-32 [8551560] Genes Dev. 1996 Mar 1;10(5):620-33 [8598291] Genes Dev. 1996 Mar 1;10(5):634-45 [8598292] Cell. 1996 Mar 22;84(6):817-9 [8601304] Genes Dev. 1996 Apr 15;10(8):905-20 [8608939] Exp Cell Res. 1996 Jun 15;225(2):277-85 [8660915] Curr Opin Genet Dev. 1996 Apr;6(2):176-84 [8722174] Mol Cell Biol. 1996 Oct;16(10):5645-54 [8816477] Cell. 1996 Oct 4;87(1):5-8 [8858142] Gene. 1996 Oct 3;174(2):315-8 [8890754] Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12845-50 [8917507] Nature. 1997 May 1;387(6628):16-7 [9139815] Nature. 1997 May 1;387(6628):43-8 [9139820] Nature. 1997 May 1;387(6628):49-55 [9139821] Nucleic Acids Res. 1998 Jul 1;26(13):3247-54 [9628926] Cell. 1998 Jun 26;93(7):1087-9 [9657139] Mol Cell Biol. 1999 Aug;19(8):5768-84 [10409764] Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 [388439] Cell. 1987 Feb 27;48(4):567-77 [3545494] Cell. 1987 Feb 27;48(4):579-87 [3028642] EMBO J. 1987 Jun;6(6):1757-63 [3649292] Methods Enzymol. 1987;154:164-75 [3323810] Cell. 1989 Mar 10;56(5):777-83 [2493990] Cell. 1989 Jun 30;57(7):1275-83 [2500253] Cell. 1990 Jan 26;60(2):307-17 [2404612] Cell. 1990 Jan 26;60(2):319-28 [2297790] Proc Natl Acad Sci U S A. 1990 Jun;87(12):4722-6 [2112746] Genes Dev. 1998 Mar 15;12(6):797-805 [9512514] Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3519-24 [9520398] Nature. 1998 Apr 23;392(6678):831-5 [9572144] Cell. 1998 May 1;93(3):321-4 [9590165] Nat Genet. 1998 Jun;19(2):187-91 [9620779] Nature. 1998 May 28;393(6683):311-2 [9620794] Nature. 1998 May 28;393(6683):386-9 [9620804] Mol Cell Biol. 1991 Dec;11(12):6306-16 [1944290] Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):227-31 [1729693] EMBO J. 1992 Jan;11(1):291-303 [1310932] EMBO J. 1992 Mar;11(3):1145-53 [1312461] Cell. 1992 Apr 17;69(2):375-84 [1568251] Cell. 1992 May 29;69(5):769-80 [1317268] Curr Opin Genet Dev. 1992 Oct;2(5):705-11 [1333855] Cell. 1993 Jan 15;72(1):29-38 [8422679] Mol Cell Biol. 1993 Mar;13(3):1805-14 [8441414] Curr Genet. 1993 May-Jun;23(5-6):547-8 [8319314] Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6125-9 [7687060] Nature. 1993 Oct 14;365(6447):666-9 [8105392] EMBO J. 1993 Dec;12(12):4885-95 [8223497] J Cell Biol. 1994 May;125(3):517-30 [8175878] Genetics. 1994 Mar;136(3):849-56 [8005439] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5913-7 [8016088] J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S2-5 [8077502] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Medications for alcohol, illicit drug, and tobacco dependence. An update of research findings. AN - 69582141; 10023607 AB - Physiologic, behavioral, and social factors contribute to dependence on alcohol, nicotine, and other drugs. During the past decade substantial research has focused on identification/development of medications to assist in reducing urge to use these substances. This article describes these agents and reviews recent research findings on them. JF - Journal of substance abuse treatment AU - Litten, R Z AU - Allen, J P AD - National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892-7003, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 105 EP - 112 VL - 16 IS - 2 SN - 0740-5472, 0740-5472 KW - Alcohol Deterrents KW - 0 KW - Bupropion KW - 01ZG3TPX31 KW - Taurine KW - 1EQV5MLY3D KW - Buprenorphine KW - 40D3SCR4GZ KW - Naltrexone KW - 5S6W795CQM KW - Methadyl Acetate KW - L59OC40KWJ KW - acamprosate KW - N4K14YGM3J KW - Index Medicus KW - Taurine -- analogs & derivatives KW - Buprenorphine -- therapeutic use KW - Bupropion -- therapeutic use KW - Humans KW - Taurine -- therapeutic use KW - Methadyl Acetate -- therapeutic use KW - Forecasting KW - Alcohol Deterrents -- therapeutic use KW - Naltrexone -- therapeutic use KW - Tobacco Use Disorder -- drug therapy KW - Substance-Related Disorders -- drug therapy KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69582141?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+substance+abuse+treatment&rft.atitle=Medications+for+alcohol%2C+illicit+drug%2C+and+tobacco+dependence.+An+update+of+research+findings.&rft.au=Litten%2C+R+Z%3BAllen%2C+J+P&rft.aulast=Litten&rft.aufirst=R&rft.date=1999-03-01&rft.volume=16&rft.issue=2&rft.spage=105&rft.isbn=&rft.btitle=&rft.title=Journal+of+substance+abuse+treatment&rft.issn=07405472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-07 N1 - Date created - 1999-04-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The significance of tetramerization in promoter recruitment by Stat5. AN - 69580807; 10022878 AB - Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Ralpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential. JF - Molecular and cellular biology AU - John, S AU - Vinkemeier, U AU - Soldaini, E AU - Darnell, J E AU - Leonard, W J AD - Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 1910 EP - 1918 VL - 19 IS - 3 SN - 0270-7306, 0270-7306 KW - DNA-Binding Proteins KW - 0 KW - Milk Proteins KW - Receptors, Interleukin-2 KW - STAT5 Transcription Factor KW - STAT5A protein, human KW - STAT5B protein, human KW - Trans-Activators KW - Tumor Suppressor Proteins KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Base Sequence KW - Humans KW - Dimerization KW - DNA -- metabolism KW - Molecular Sequence Data KW - Cell Line, Transformed KW - Response Elements KW - Transcriptional Activation KW - Mutagenesis KW - Binding Sites KW - Trans-Activators -- metabolism KW - Promoter Regions, Genetic KW - Trans-Activators -- genetics KW - DNA-Binding Proteins -- genetics KW - Receptors, Interleukin-2 -- genetics KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69580807?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=The+significance+of+tetramerization+in+promoter+recruitment+by+Stat5.&rft.au=John%2C+S%3BVinkemeier%2C+U%3BSoldaini%2C+E%3BDarnell%2C+J+E%3BLeonard%2C+W+J&rft.aulast=John&rft.aufirst=S&rft.date=1999-03-01&rft.volume=19&rft.issue=3&rft.spage=1910&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Immunity. 1995 Apr;2(4):331-9 [7719938] Immunity. 1995 Apr;2(4):321-9 [7719937] Genes Dev. 1995 Apr 15;9(8):984-94 [7774815] Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5482-6 [7777534] EMBO J. 1995 Jun 1;14(11):2527-35 [7781605] Immunity. 1995 Jun;2(6):689-97 [7796300] Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7192-6 [7543676] Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10772-6 [7479881] Cell. 1996 Feb 9;84(3):331-4 [8608586] Cell. 1996 Feb 9;84(3):421-30 [8608596] J Biol Chem. 1996 May 3;271(18):10738-44 [8631883] Science. 1996 Aug 9;273(5276):794-7 [8670419] Mol Cell Biol. 1996 Oct;16(10):5811-20 [8816495] EMBO J. 1996 Oct 15;15(20):5616-26 [8896455] EMBO J. 1996 Oct 15;15(20):5627-35 [8896456] Mol Cell Biol. 1996 Dec;16(12):6829-40 [8943338] J Mol Biol. 1997 Jan 10;265(1):68-84 [8995525] Curr Opin Cell Biol. 1997 Apr;9(2):233-9 [9069254] J Interferon Cytokine Res. 1997 Mar;17(3):121-34 [9085936] Science. 1997 Sep 12;277(5332):1630-5 [9287210] Immunity. 1997 Nov;7(5):691-701 [9390692] J Biol Chem. 1997 Dec 12;272(50):31821-8 [9395528] J Biol Chem. 1998 Apr 24;273(17):10719-25 [9553136] Annu Rev Immunol. 1998;16:293-322 [9597132] Cytokine Growth Factor Rev. 1997 Dec;8(4):313-32 [9620644] J Exp Med. 1998 Dec 7;188(11):2067-74 [9841920] Science. 1998 Feb 13;279(5353):1048-52 [9461439] Nature. 1994 May 26;369(6478):330-3 [8183373] Nature. 1994 Jul 14;370(6485):151-3 [8022485] Nature. 1994 Jul 14;370(6485):153-7 [8022486] Science. 1994 Nov 11;266(5187):1039-42 [7973657] Science. 1994 Nov 11;266(5187):1042-5 [7973658] Science. 1994 Nov 11;266(5187):1045-7 [7973659] EMBO J. 1994 Dec 1;13(23):5605-15 [7988557] Eur J Immunol. 1994 Dec;24(12):3082-6 [7528668] Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3041-5 [7708771] J Biol Chem. 1995 May 5;270(18):10743-53 [7738013] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Identification of protein instability determinants in the carboxy-terminal region of c-Myb removed as a result of retroviral integration in murine monocytic leukemias. AN - 69575844; 9971784 AB - The c-myb oncogene has been a target of retroviral insertional mutagenesis in murine monocytic leukemias. One mechanism by which c-myb can be activated is through the integration of a retroviral provirus into the central portion of the locus, causing premature termination of c-myb transcription and translation. We had previously shown that a leukemia-specific c-Myb protein, truncated at the site of proviral integration by 248 amino acids, had approximately a fourfold-increased half-life compared to the normal c-Myb protein, due to its ability to escape rapid degradation by the ubiquitin-26S proteasome pathway. Here we provide evidence for the existence of more than one instability determinant in the carboxy-terminal region of the wild-type protein, which appear to act independently of each other. The data were derived from examination of premature termination mutants and deletion mutants of the normal protein, as well as analysis of another carboxy-terminally truncated protein expressed in leukemia. Evidence is provided that one instability determinant is located in the terminal 87 amino acids of the protein and another is located in the vicinity of the internal region that has leucine zipper homology. In leukemias, different degrees of protein stability are attained following proviral integration depending upon how many determinants are removed. Interestingly, although PEST sequences (rich in proline, glutamine, serine, and threonine), often associated with degradation, are found in c-Myb, deletion of PEST-containing regions had no effect on protein turnover. This study provides further insight into how inappropriate expression of c-Myb may contribute to leukemogenesis. In addition, it will facilitate further studies aimed at characterizing the specific role of individual regions of the normal protein in targeting to the 26S proteasome. JF - Journal of virology AU - Bies, J AU - Nazarov, V AU - Wolff, L AD - Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 2038 EP - 2044 VL - 73 IS - 3 SN - 0022-538X, 0022-538X KW - Proto-Oncogene Proteins KW - 0 KW - Proto-Oncogene Proteins c-myb KW - RNA, Messenger KW - Trans-Activators KW - Index Medicus KW - Animals KW - COS Cells KW - RNA, Messenger -- analysis KW - Mice KW - Leucine Zippers KW - Structure-Activity Relationship KW - Mice, Inbred DBA KW - Trans-Activators -- metabolism KW - Trans-Activators -- genetics KW - Proto-Oncogene Proteins -- chemistry KW - Trans-Activators -- chemistry KW - Proto-Oncogene Proteins -- metabolism KW - Virus Integration KW - Retroviridae -- genetics KW - Proto-Oncogene Proteins -- genetics KW - Leukemia, Myeloid -- virology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69575844?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Identification+of+protein+instability+determinants+in+the+carboxy-terminal+region+of+c-Myb+removed+as+a+result+of+retroviral+integration+in+murine+monocytic+leukemias.&rft.au=Bies%2C+J%3BNazarov%2C+V%3BWolff%2C+L&rft.aulast=Bies&rft.aufirst=J&rft.date=1999-03-01&rft.volume=73&rft.issue=3&rft.spage=2038&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-04 N1 - Date created - 1999-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Oncogene. 1997 Dec 11;15(24):2939-49 [9416837] J Virol. 1997 Sep;71(9):6526-33 [9261372] J Virol. 1983 Jan;45(1):1-9 [6296423] Proc Natl Acad Sci U S A. 1986 May;83(10):3204-8 [3010282] J Virol. 1987 Dec;61(12):3721-5 [2824810] Mol Cell Biol. 1988 Jun;8(6):2504-12 [3043180] J Virol. 1991 Jul;65(7):3607-16 [1645785] Oncogene. 1991 Sep;6(9):1549-53 [1923521] Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3088-92 [1557416] Mol Cell Biol. 1992 Jun;12(6):2493-500 [1588953] J Virol. 1992 Oct;66(10):6035-44 [1527851] Science. 1992 Dec 18;258(5090):1941-4 [1470918] Int J Biochem. 1993 Apr;25(4):479-82 [8096823] Cell. 1994 Sep 9;78(5):787-98 [8087846] J Biol Chem. 1994 Oct 28;269(43):26822-9 [7929419] Cell Growth Differ. 1995 Jan;6(1):59-68 [7536440] J Virol. 1995 Jun;69(6):3885-8 [7745739] Oncogene. 1995 Oct 19;11(8):1631-8 [7478588] Curr Top Microbiol Immunol. 1996;211:191-9 [8585950] Oncogene. 1996 Jan 18;12(2):355-63 [8570212] Int J Clin Lab Res. 1996;26(1):24-32 [8739852] Trends Biochem Sci. 1996 Jul;21(7):267-71 [8755249] Virology. 1996 Oct 1;224(1):224-34 [8862417] Trends Biochem Sci. 1996 Mar;21(3):96-102 [8882582] Oncogene. 1997 Jan 16;14(2):203-12 [9010222] Nature. 1997 May 15;387(6630):299-303 [9153396] Crit Rev Oncog. 1996;7(3-4):245-60 [9258605] Mol Cell Biol. 1998 Feb;18(2):989-1002 [9447996] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the effects of charge cluster mutations in adeno-associated virus Rep68 protein in vitro. AN - 69573570; 9971790 AB - The Rep78 and Rep68 proteins of adeno-associated virus type 2 (AAV) are multifunctional proteins which are required for viral replication, regulation of AAV promoters, and preferential integration of the AAV genome into a region of human chromosome 19. These proteins bind the hairpin structures formed by the AAV inverted terminal repeat (ITR) origins of replication, make site- and strand-specific endonuclease cuts within the AAV ITRs, and display nucleoside triphosphate-dependent helicase activities. Additionally, several mutant Rep proteins display negative dominance in helicase and/or endonuclease assays when they are mixed with wild-type Rep78 or Rep68, suggesting that multimerization may be required for the helicase and endonuclease functions. Using overlap extension PCR mutagenesis, we introduced mutations within clusters of charged residues throughout the Rep68 moiety of a maltose binding protein-Rep68 fusion protein (MBP-Rep68Delta) expressed in Escherichia coli cells. Several mutations disrupted the endonuclease and helicase activities; however, only one amino-terminal-charge cluster mutant protein (D40A-D42A-D44A) completely lost AAV hairpin DNA binding activity. Charge cluster mutations within two other regions abolished both endonuclease and helicase activities. One region contains a predicted alpha-helical structure (amino acids 371 to 393), and the other contains a putative 3,4 heptad repeat (coiled-coil) structure (amino acids 441 to 483). The defects displayed by these mutant proteins correlated with a weaker association with wild-type Rep68 protein, as measured in coimmunoprecipitation assays. These experiments suggest that these regions of the Rep molecule are involved in Rep oligomerization events critical for both helicase and endonuclease activities. JF - Journal of virology AU - Davis, M D AU - Wonderling, R S AU - Walker, S L AU - Owens, R A AD - Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 2084 EP - 2093 VL - 73 IS - 3 SN - 0022-538X, 0022-538X KW - Carrier Proteins KW - 0 KW - DNA-Binding Proteins KW - Escherichia coli Proteins KW - Maltose-Binding Proteins KW - Monosaccharide Transport Proteins KW - Recombinant Fusion Proteins KW - Viral Proteins KW - maltose transport system, E coli KW - rep proteins, Adeno-associated virus 2 KW - 137750-19-7 KW - DNA KW - 9007-49-2 KW - Endonucleases KW - EC 3.1.- KW - DNA Helicases KW - EC 3.6.4.- KW - Index Medicus KW - Endonucleases -- metabolism KW - Carrier Proteins -- metabolism KW - DNA Helicases -- metabolism KW - Humans KW - DNA -- metabolism KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Recombinant Fusion Proteins -- chemistry KW - Mutagenesis KW - Carrier Proteins -- isolation & purification KW - DNA-Binding Proteins -- chemistry KW - Viral Proteins -- chemistry KW - ATP-Binding Cassette Transporters KW - Dependovirus -- chemistry KW - DNA-Binding Proteins -- physiology KW - Viral Proteins -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69573570?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Analysis+of+the+effects+of+charge+cluster+mutations+in+adeno-associated+virus+Rep68+protein+in+vitro.&rft.au=Davis%2C+M+D%3BWonderling%2C+R+S%3BWalker%2C+S+L%3BOwens%2C+R+A&rft.aulast=Davis&rft.aufirst=M&rft.date=1999-03-01&rft.volume=73&rft.issue=3&rft.spage=2084&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-04 N1 - Date created - 1999-03-04 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gene Ther. 1994 May;1(3):165-9 [7584077] J Virol. 1996 Apr;70(4):2440-8 [8642672] J Virol. 1992 Feb;66(2):1119-28 [1309894] J Virol. 1992 Feb;66(2):1236-40 [1309900] J Virol. 1992 Jul;66(7):4050-7 [1318396] Biochem Biophys Res Commun. 1996 Mar 18;220(2):294-9 [8645299] J Virol. 1996 Mar;70(3):1542-53 [8627673] J Virol. 1996 Jul;70(7):4783-6 [8676507] Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8350-5 [8710874] Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7966-72 [8755586] J Virol. 1997 Mar;71(3):2528-34 [9032395] J Virol. 1997 Apr;71(4):2722-30 [9060625] J Virol. 1997 Jun;71(6):4461-71 [9151837] J Virol. 1997 Sep;71(9):6996-7004 [9261429] Virology. 1997 Sep 15;236(1):167-76 [9299629] J Virol. 1998 Jun;72(6):4874-81 [9573254] Biophys J. 1967 Mar;7(2):121-35 [6048867] Proc Natl Acad Sci U S A. 1976 Mar;73(3):742-6 [1062784] Virology. 1977 May 15;78(2):488-99 [867815] J Virol. 1983 Feb;45(2):555-64 [6300419] Cell. 1983 May;33(1):135-43 [6088052] J Mol Biol. 1984 Oct 15;179(1):1-20 [6094825] J Virol. 1986 Feb;57(2):656-69 [3502703] J Virol. 1986 Jun;58(3):921-36 [3701931] J Virol. 1986 Oct;60(1):251-8 [3018288] EMBO J. 1992 Dec;11(13):5071-8 [1334463] J Virol. 1993 Feb;67(2):989-96 [8380474] J Virol. 1993 Feb;67(2):997-1005 [8380475] Genes Dev. 1993 Jun;7(6):1047-58 [8504929] J Virol. 1993 Jul;67(7):4442-7 [8389942] Nucleic Acids Res. 1993 Jun 11;21(11):2541-7 [8332451] J Virol. 1994 Feb;68(2):797-804 [8289383] J Virol. 1994 May;68(5):2947-57 [8151765] Cancer Lett. 1994 Jun 30;81(2):129-36 [8012930] Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5808-12 [8016070] J Virol. 1994 Aug;68(8):4998-5006 [8035499] Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10039-43 [7937833] J Virol. 1995 Apr;69(4):2038-46 [7884849] J Virol. 1995 Jun;69(6):3542-8 [7538173] Biochem Biophys Res Commun. 1995 May 25;210(3):717-25 [7763245] Virology. 1995 Oct 1;212(2):562-73 [7571426] J Virol. 1986 Dec;60(3):823-32 [3023672] Mol Cell Biol. 1986 Aug;6(8):2884-94 [3491293] Mol Cell Biol. 1987 Apr;7(4):1320-5 [3037312] Virology. 1987 Nov;161(1):18-28 [2823460] Proc Natl Acad Sci U S A. 1988 Dec;85(24):9396-400 [2849101] J Virol. 1989 Jul;63(7):3095-104 [2542617] Virology. 1989 Jul;171(1):239-47 [2545030] Gene. 1989 Apr 15;77(1):51-9 [2744487] Proc Natl Acad Sci U S A. 1989 Aug;86(15):5698-702 [2569737] J Virol. 1989 Oct;63(10):4450-4 [2550677] Cell. 1990 Jan 12;60(1):105-13 [2153052] Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5 [2156265] Oncogene. 1990 Jan;5(1):85-95 [2181379] Proteins. 1990;7(1):1-15 [2184436] Cell. 1990 May 4;61(3):447-57 [2159383] Annu Rev Biochem. 1990;59:289-329 [2165383] J Virol. 1990 Dec;64(12):6204-13 [2173787] J Virol. 1991 Jan;65(1):396-404 [1845899] Trends Biochem Sci. 1990 Nov;15(11):430-4 [2126155] J Mol Biol. 1991 Feb 20;217(4):721-9 [2005621] Nature. 1991 May 2;351(6321):78-80 [1851252] Virology. 1991 Sep;184(1):14-22 [1651588] Genes Dev. 1991 Sep;5(9):1553-67 [1884998] Genomics. 1991 Jul;10(3):831-4 [1653762] J Virol. 1992 Oct;66(10):6058-69 [1326656] J Virol. 1995 Nov;69(11):6787-96 [7474090] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin. AN - 69566490; 9952390 AB - To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions. JF - The Journal of infectious diseases AU - Cooper, P J AU - Awadzi, K AU - Ottesen, E A AU - Remick, D AU - Nutman, T B AD - Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892-0425, USA. pcooper@atlas.niaid.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 738 EP - 742 VL - 179 IS - 3 SN - 0022-1899, 0022-1899 KW - Anthelmintics KW - 0 KW - Interleukin-5 KW - Placebos KW - Ivermectin KW - 70288-86-7 KW - Abridged Index Medicus KW - Index Medicus KW - Ghana KW - Animals KW - Double-Blind Method KW - Dose-Response Relationship, Drug KW - Humans KW - Interleukin-5 -- blood KW - Male KW - Agranulocytosis -- chemically induced KW - Cell Degranulation -- drug effects KW - Onchocerciasis -- drug therapy KW - Onchocerca volvulus KW - Ivermectin -- adverse effects KW - Eosinophils -- physiology KW - Anthelmintics -- pharmacokinetics KW - Eosinophils -- drug effects KW - Anthelmintics -- adverse effects KW - Ivermectin -- pharmacokinetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69566490?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+infectious+diseases&rft.atitle=Eosinophil+sequestration+and+activation+are+associated+with+the+onset+and+severity+of+systemic+adverse+reactions+following+the+treatment+of+onchocerciasis+with+ivermectin.&rft.au=Cooper%2C+P+J%3BAwadzi%2C+K%3BOttesen%2C+E+A%3BRemick%2C+D%3BNutman%2C+T+B&rft.aulast=Cooper&rft.aufirst=P&rft.date=1999-03-01&rft.volume=179&rft.issue=3&rft.spage=738&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+infectious+diseases&rft.issn=00221899&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-30 N1 - Date created - 1999-03-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Power and sample size for testing homogeneity of relative risks in prospective studies. AN - 69512328; 11318170 AB - Power and sample-size formulas for testing the homogeneity of relative risks using the score method are presented. The homogeneity score test (Gart, 1985, Biometrika 72, 673-677) is formally equivalent to the Pearson chi-square test, although they look different. Results of this paper may be useful in assessing the validity of the model of a common relative risk before combining several 2 x 2 tables or in designing a prospective study for detecting heterogeneity of relative risks. JF - Biometrics AU - Nam, J M AD - Biostatistics Branch, National Cancer Institute, Rockville, Maryland 20892-7368, USA. namj@epndce.nci.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 289 EP - 293 VL - 55 IS - 1 SN - 0006-341X, 0006-341X KW - Contraceptives, Oral KW - 0 KW - Index Medicus KW - Contraceptives, Oral -- adverse effects KW - Animals KW - Prospective Studies KW - Humans KW - Bacteriuria -- etiology KW - Models, Statistical KW - Mice KW - Sample Size KW - Likelihood Functions KW - Male KW - Female KW - Carcinogenicity Tests -- statistics & numerical data KW - Risk KW - Biometry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69512328?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Power+and+sample+size+for+testing+homogeneity+of+relative+risks+in+prospective+studies.&rft.au=Nam%2C+J+M&rft.aulast=Nam&rft.aufirst=J&rft.date=1999-03-01&rft.volume=55&rft.issue=1&rft.spage=289&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sister chromatid exchange formation in mammalian cells is modulated by deoxyribonucleotide pool imbalance. AN - 69509293; 11225054 AB - The formation of sister chromatid exchanges (SEC) is closely related to DNA replication which is dependent on the proper balance of deoxyribonucleic triphosphates. Since DNA precursor imbalances can influence DNA metabolism, the relationship between 5-bromodeoxyuridine (BrdUrd)-induction of SCE and nucleotide pool imbalance was examined in Syrian hamster fetal cells (HFC) and mouse 3T6 cell line. In exponentially growing HFC, deoxyadenosine and deoxyguanosine stimulated the formation of SCE, while deoxycytidine (dCyd) prevented the dose dependent increase of SCE caused by BrdUrd. Cell growth inhibition produced by amino acid deprivation resulted in a significant increase in SCE as compared to exponentially growing cultures. This SCE enhancement was reduced by dCyd in HFC and did not occur in mouse 3T6 clone deficient in deoxycytidine deaminase. The modulation of SCE by DNA precursors is consistent with the induction of BrdUrd mutagenesis in mammalian cells and raises the possibility that common DNA changes are responsible for the induction of SCE and mutation in mammalian cells. JF - Somatic cell and molecular genetics AU - Popescu, N C AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-4255, USA. Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 101 EP - 108 VL - 25 IS - 2 SN - 0740-7750, 0740-7750 KW - Deoxyribonucleotides KW - 0 KW - Floxuridine KW - 039LU44I5M KW - Bromodeoxyuridine KW - G34N38R2N1 KW - Index Medicus KW - Animals KW - Bromodeoxyuridine -- pharmacology KW - Floxuridine -- pharmacology KW - Cells, Cultured KW - Cricetinae KW - Sister Chromatid Exchange -- drug effects KW - Deoxyribonucleotides -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69509293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Somatic+cell+and+molecular+genetics&rft.atitle=Sister+chromatid+exchange+formation+in+mammalian+cells+is+modulated+by+deoxyribonucleotide+pool+imbalance.&rft.au=Popescu%2C+N+C&rft.aulast=Popescu&rft.aufirst=N&rft.date=1999-03-01&rft.volume=25&rft.issue=2&rft.spage=101&rft.isbn=&rft.btitle=&rft.title=Somatic+cell+and+molecular+genetics&rft.issn=07407750&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-03-08 N1 - Date created - 2001-02-27 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Use of summary measures to adjust for informative missingness in repeated measures data with random effects. AN - 69508642; 11318181 AB - We discuss how to apply the conditional informative missing model of Wu and Bailey (1989, Biometrics 45, 939-955) to the setting where the probability of missing a visit depends on the random effects of the primary response in a time-dependent fashion. This includes the case where the probability of missing a visit depends on the true value of the primary response. Summary measures for missingness that are weighted sums of the indicators of missed visits are derived for these situations. These summary measures are then incorporated as covariates in a random effects model for the primary response. This approach is illustrated by analyzing data collected from a trial of heroin addicts where missed visits are informative about drug test results. Simulations of realistic experiments indicate that these time-dependent summary measures also work well under a variety of informative censoring models. These summary measures can achieve large reductions in estimation bias and mean squared errors relative to those obtained by using other summary measures. JF - Biometrics AU - Wu, M C AU - Follmann, D A AD - Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892-7938, USA. mwu@cu.nih.gov Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 75 EP - 84 VL - 55 IS - 1 SN - 0006-341X, 0006-341X KW - Narcotic Antagonists KW - 0 KW - Index Medicus KW - Probability KW - Narcotic Antagonists -- therapeutic use KW - Heroin Dependence -- urine KW - Epidemiologic Methods KW - Humans KW - Heroin Dependence -- drug therapy KW - Linear Models KW - Models, Statistical KW - Clinical Trials as Topic -- statistics & numerical data KW - Biometry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69508642?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biometrics&rft.atitle=Use+of+summary+measures+to+adjust+for+informative+missingness+in+repeated+measures+data+with+random+effects.&rft.au=Wu%2C+M+C%3BFollmann%2C+D+A&rft.aulast=Wu&rft.aufirst=M&rft.date=1999-03-01&rft.volume=55&rft.issue=1&rft.spage=75&rft.isbn=&rft.btitle=&rft.title=Biometrics&rft.issn=0006341X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-05-21 N1 - Date created - 2001-04-24 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Raman chemical imaging spectroscopy AN - 52343429; 2000-048378 JF - Analytical Chemistry (Washington, DC) AU - Schaeberle, Michael D AU - Morris, Hannah R AU - Turner, John F, II AU - Treado, Patrick J Y1 - 1999/03// PY - 1999 DA - March 1999 SP - 175 EP - 181 PB - American Chemical Society, Washington, DC VL - 71 IS - 5 SN - 0003-2700, 0003-2700 KW - imagery KW - chemical analysis KW - technology KW - anatase KW - silicon KW - layered materials KW - multispectral analysis KW - molecular structure KW - spatial distribution KW - Raman spectroscopy KW - transfer functions KW - future KW - rutile KW - oxides KW - components KW - spectroscopy KW - geochemistry KW - image analysis KW - filters KW - digitization KW - 02A:General geochemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/52343429?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ageorefmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Analytical+Chemistry+%28Washington%2C+DC%29&rft.atitle=Raman+chemical+imaging+spectroscopy&rft.au=Schaeberle%2C+Michael+D%3BMorris%2C+Hannah+R%3BTurner%2C+John+F%2C+II%3BTreado%2C+Patrick+J&rft.aulast=Schaeberle&rft.aufirst=Michael&rft.date=1999-03-01&rft.volume=71&rft.issue=5&rft.spage=175&rft.isbn=&rft.btitle=&rft.title=Analytical+Chemistry+%28Washington%2C+DC%29&rft.issn=00032700&rft_id=info:doi/ L2 - http://www3.interscience.wiley.com/cgi-bin/jhome/38876 LA - English DB - GeoRef N1 - Copyright - GeoRef, Copyright 2012, American Geosciences Institute. N1 - Date revised - 2000-01-01 N1 - Number of references - 33 N1 - PubXState - DC N1 - Document feature - illus. N1 - Last updated - 2012-06-07 N1 - SubjectsTermNotLitGenreText - anatase; chemical analysis; components; digitization; filters; future; geochemistry; image analysis; imagery; layered materials; molecular structure; multispectral analysis; oxides; Raman spectroscopy; rutile; silicon; spatial distribution; spectroscopy; technology; transfer functions ER - TY - JOUR T1 - Neuroimaging and Human Genetics AN - 19524921; 8067775 AB - The past few years have seen a rapid expansion of the application of neuroimaging tools to the investigation of the genetics of brain structure and function. In this chapter, we will (1) highlight the most important steps during the historical development of this research field, (2) explain the major purposes of using neuroimaging in genetic research, (3) address methodological issues that are relevant with regard to the application of neuroimaging in genetic research, (4) give an overview of the present state-of-research, and (5) provide several examples of how neuroimaging was successfully applied. Further Readings M. Buchsbaum, Self-regulation of stimulus intensity: Augmenting reducing and the average evoked response. In: G.E. Schwartz and D. Shapiro, Editors, 'Consciousness and self-regulation', Plenum Press, New York (1976). D. Durstewitz and J.K. Seamans, The computational role of dopamine D1 receptors in working memory, Neural Netw. 15 (2002), pp. 561-572. M. Higuchi, H. Arai, T. Nakagawa, S. Higuchi, T. Muramatsu, S. Matsushita, Y. Kosaka, M. Itoh and H. Sasaki, Regional cerebral glucose utilization is modulated by the dosage of apolipoprotein E type 4 allele and alpha1-antichymotrypsin type A allele in Alzheimer's disease, Neuroreport 8 (1997), pp. 2639-2643. Y. Hirayasu, S. Tanaka, M.E. Shenton, D.F. Salisbury, M.A. De Santis, J.J. Levitt, C. Wible, D. Yurgelun-Todd, R. Kikinis, F.A. Jolesz and R.W. McCarley, Prefrontal gray matter volume reduction in first episode schizophrenia, Cereb. Cortex 11 (2001), pp. 374-381. K.S. Kendler and S.H. Aggen, Time, memory and the heritability of major depression, Psychol. Med. 31 (2001), pp. 923-928. T. Kiesepa, T. Partonen, J. Haukka, J. Kaprio and J. Lonnquist, High concordance of bipolar I disorder in a nationwide sample of twins, Am. J. Psychiat. 161 (2004), pp. 1814-1821. J.J. Kim, S. Mohamed, N.C. Andreasen, D.S. O'Leary, G.L. Watkins, L.L. Boles Ponto and R.D. Hichwa, Regional neural dysfunctions in chronic schizophrenia studied with positron emission tomography, Am. J. Psychiat. 157 (2000), pp. 542-548. E. Kinnunen, J. Juntunen, L. Ketonen, S. Koskimies, Y.T. Konttinen, T. Salmi, M. Koskenvuo and J. Kaprio, Genetic susceptibility to multiple sclerosis. A co-twin study of a nationwide series, Arch. Neurol. 45 (1988), pp. 1108-1111. N.J. Tramo, W.C. Loftus, T.A. Stukel, R.L. Green, J.B. Weaver, Gazzaniga and M.S., Brain size, head size, and intelligent quotient in monozygotic twins, Neurology 50 (1998), pp. 1246-1252. Abstract | Full Text + Links | PDF (1073 K) | View Record in Scopus | Cited By in Scopus (63) View Record in Scopus | Cited By in Scopus (18) View Record in Scopus | Cited By in Scopus (61) View Record in Scopus | Cited By in Scopus (4) View Record in Scopus | Cited By in Scopus (69) View Record in Scopus | Cited By in Scopus (30) JF - International Journal of Radiation Oncology, Biology, & Physics AU - Winterer, Georg AU - Hariri, Ahmad R AU - Goldman, David AU - Weinberger, Daniel R AD - Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 325 EP - 383 PB - Elsevier Science, Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 43 IS - 4 SN - 0360-3016, 0360-3016 KW - Genetics Abstracts; Biotechnology and Bioengineering Abstracts; CSA Neurosciences Abstracts KW - Neuroimaging KW - Alzheimer's disease KW - Apolipoprotein E KW - Dopamine D1 receptors KW - Glucose KW - Glucose metabolism KW - Short term memory KW - Schizophrenia KW - Mental disorders KW - Consciousness KW - Memory KW - Cortex KW - Structure-function relationships KW - Positron emission tomography KW - Computational neuroscience KW - Depression KW - Head KW - Multiple sclerosis KW - Brain KW - Functional anatomy KW - Neurodegenerative diseases KW - Twins KW - Reviews KW - Language KW - Heritability KW - Cortex (prefrontal) KW - Substantia grisea KW - G 07880:Human Genetics KW - N3 11023:Neurogenetics KW - W 30960:Bioinformatics & Computer Applications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/19524921?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Neuroimaging+and+Human+Genetics&rft.au=Winterer%2C+Georg%3BHariri%2C+Ahmad+R%3BGoldman%2C+David%3BWeinberger%2C+Daniel+R&rft.aulast=Winterer&rft.aufirst=Georg&rft.date=1999-03-01&rft.volume=43&rft.issue=4&rft.spage=325&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2FS0074-7742%2805%2967010-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Neuroimaging; Apolipoprotein E; Alzheimer's disease; Glucose; Dopamine D1 receptors; Glucose metabolism; Short term memory; Schizophrenia; Memory; Consciousness; Mental disorders; Cortex; Structure-function relationships; Positron emission tomography; Computational neuroscience; Depression; Head; Multiple sclerosis; Brain; Functional anatomy; Neurodegenerative diseases; Twins; Reviews; Language; Cortex (prefrontal); Heritability; Substantia grisea DO - http://dx.doi.org/10.1016/S0074-7742(05)67010-9 ER - TY - JOUR T1 - Induction of Anti-Tumor Immunity Elicited by Tumor Cells Expressing a Murine LFA-3 Analog via a Recombinant Vaccinia Virus AN - 17579598; 4487712 AB - T cell activation requires binding of the T cell receptor to the major histocompatibility molecule-peptide complex in the presence of adhesion and/or costimulatory molecules such as B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), and CD2. The major ligand of CD2 is CD48, the murine analog of human leukocyte function-associated antigen 3 (LFA-3). To determine the effect of LFA-3 expression on the immunogenicity of tumor cells, we constructed a recombinant vaccinia virus containing the murine LFA-3 gene (designated rV-LFA-3). rV-LFA-3 was shown to be functional in vitro in terms of expression of LFA-3, T cell proliferation, adhesion, and cytotoxicity. Subcutaneous inoculation of rV-LFA-3-infected murine colon adenocarcinoma tumor cells (MC38) into immunocompetent syngeneic C57BL/6 mice resulted in complete lack of tumor growth. Inoculation of MC38 cells infected with equal doses of control wild-type vaccinia virus resulted in tumor growth in all animals. In addition, partial immunological protection was demonstrated against subsequent challenge with uninfected parental tumor cells up to 56 days after vaccination with rV-LFA-3-infected cells. Anti-tumor memory was also demonstrated by using gamma -irradiated MC38 cells and cells from another carcinoma model (CT26). These studies demonstrate that expression of LFA-3 via a poxvirus vector can be used to induce anti-tumor immunity. JF - Human Gene Therapy AU - Lorenz, MGO AU - Kantor, JA AU - Schlom, J AU - Hodge, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, 10 Center Drive, Building 10, Room 8B07, Bethesda, MD 20892, USA, js141c@nih.gov Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 623 EP - 631 VL - 10 IS - 4 SN - 1043-0342, 1043-0342 KW - C57BL/6 mice KW - man KW - B7-1 antigen KW - B7-2 antigen KW - CD54 antigen KW - CD86 antigen KW - LFA-3 antigen KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Gene therapy KW - Colon KW - Adenocarcinoma KW - Tumor cells KW - W3 33170:Cellular based KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17579598?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Induction+of+Anti-Tumor+Immunity+Elicited+by+Tumor+Cells+Expressing+a+Murine+LFA-3+Analog+via+a+Recombinant+Vaccinia+Virus&rft.au=Lorenz%2C+MGO%3BKantor%2C+JA%3BSchlom%2C+J%3BHodge%2C+J+W&rft.aulast=Lorenz&rft.aufirst=MGO&rft.date=1999-03-01&rft.volume=10&rft.issue=4&rft.spage=623&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/10.1089%2F10430349950018698 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Tumor cells; Adenocarcinoma; Colon; Gene therapy DO - http://dx.doi.org/10.1089/10430349950018698 ER - TY - JOUR T1 - Mutational consequences of replication of M13mp7l2 constructs containing cis-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyadenosine adducts AN - 17266018; 4537142 AB - The four adducts that arise by cis ring opening of the four optically active benzo[a]pyrene diol epoxides by the exocyclic N super(6)-amino group of deoxyadenosine were incorporated synthetically into each of two different oligonucleotide 16-mers, 5 theta -TTTXGAGTCTGCTCCC-3 theta [context I(A)] and 5 theta -CAGXTTTAGAGTCTGC-3 theta [context II(A)], at the X position. The eight resultant oligonucleotides were separately ligated into bacteriophage M13mp7L2 and replicated in Escherichia coli that had been SOS-induced, and the progeny were analyzed to evaluate the consequences of replication past these adducts. The presence of these adducts reduced plaque yields substantially. However, the progeny obtained exhibited high frequencies of base substitution mutation ranging from 9 to 68%, depending upon the individual adduct and the sequence context in which it was placed. For most of the adducts, A arrow right T transversion was the mutation found most frequently in either sequence context, and mutation frequencies in context I(A) were always substantially greater than those in context II(A). In context I(A), adducts with an R configuration at the site of nucleoside attachment were more mutagenic than those with an S configuration. In both sequence contexts that were studied, the cis adduct arising from the (7S,8R)-diol (9S,10R)-epoxide was the most mutagenic adduct. These findings clearly show that individual mutation frequencies are determined by the combined effects of both adduct structure and sequence context. JF - Chemical Research in Toxicology AU - Page, JE AU - Pilcher, A S AU - Yagi, H AU - Sayer, J M AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-FCRDC, Frederick, Maryland 21702, USA Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 258 EP - 263 VL - 12 IS - 3 SN - 0893-228X, 0893-228X KW - benzo(a)pyrene-7,8-diol 9,10-epoxide KW - deoxyadenosine KW - Toxicology Abstracts KW - DNA adducts KW - Polycyclic aromatic hydrocarbons KW - Mutagenicity KW - Benzo(a)pyrene KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17266018?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Mutational+consequences+of+replication+of+M13mp7l2+constructs+containing+cis-opened+benzo%5Ba%5Dpyrene+7%2C8-diol+9%2C10-epoxide-deoxyadenosine+adducts&rft.au=Page%2C+JE%3BPilcher%2C+A+S%3BYagi%2C+H%3BSayer%2C+J+M%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Page&rft.aufirst=JE&rft.date=1999-03-01&rft.volume=12&rft.issue=3&rft.spage=258&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mutagenicity; Benzo(a)pyrene; DNA adducts; Polycyclic aromatic hydrocarbons ER - TY - JOUR T1 - Curvature of Dinucleotide Poised for Formation of Trinucleotide in Transcription with Escherichia coli RNA Polymerase AN - 17241773; 4516695 AB - A frequently used schematic model of transcriptional elongation shows an RNA polymerase molecule moving along a linear DNA. This model is of course highly idealized and not compatible with promoter sequences and regulatory proteins located some distance away from the point of transcription initiation. These circumstances lead to the expectation of curvature along the DNA strand and require looping between sometimes distant points. We have now shown curvature in a dinucleotide formed at the very onset of transcription when it is poised for reaction with a mononucleotide to form a trinucleotide. The curvature became evident from the demonstration that a metal ion bound with a mononucleotide in the i+1 (elongation) site is approximately equidistant from bases at the 5' end (i-1 site) and 3' end (i site) of the dinucleotide. Similar results were obtained with three different dinucleotides and four mononucleotides. Curvature of the RNA initiate may reflect curvature of the DNA to which it is bound. These studies show curvature to be a significant feature in the interaction between DNA template and RNA elongate even at the very beginning of transcription. JF - Biochemistry (Washington) AU - Garland, C S AU - Tarien, E AU - Nirmala, R AU - Clark, P AU - Rifkind, J AU - Eichhorn, G L AD - Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 3421 EP - 3425 VL - 38 IS - 11 SN - 0006-2960, 0006-2960 KW - dinucleotides KW - transcription KW - trinucleotides KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-directed RNA polymerase KW - Escherichia coli KW - Transcription KW - N 14721:RNA polymerases KW - J 02726:RNA and ribosomes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17241773?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry+%28Washington%29&rft.atitle=Curvature+of+Dinucleotide+Poised+for+Formation+of+Trinucleotide+in+Transcription+with+Escherichia+coli+RNA+Polymerase&rft.au=Garland%2C+C+S%3BTarien%2C+E%3BNirmala%2C+R%3BClark%2C+P%3BRifkind%2C+J%3BEichhorn%2C+G+L&rft.aulast=Garland&rft.aufirst=C&rft.date=1999-03-01&rft.volume=38&rft.issue=11&rft.spage=3421&rft.isbn=&rft.btitle=&rft.title=Biochemistry+%28Washington%29&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed RNA polymerase; Transcription ER - TY - JOUR T1 - Microarrays and toxicology: The advent of toxicogenomics AN - 17236966; 4510713 AB - The availability of genome-scale DNA sequence information and reagents has radically altered life-science research. This revolution has led to the development of a new scientific subdiscipline derived from a combination of the fields of toxicology and genomics. This subdiscipline, termed toxicogenomics, is concerned with the identification of potential human and environmental toxicants, and their putative mechanisms of action, through the use of genomics resources. One such resource is DNA microarrays or "chips," which allow the monitoring of the expression levels of thousands of genes simultaneously. Here we propose a general method by which gene expression, as measured by cDNA microarrays, can be used as a highly sensitive and informative marker for toxicity. Our purpose is to acquaint the reader with the development and current state of microarray technology and to present our view of the usefulness of microarrays to the field of toxicology. JF - Molecular Carcinogenesis AU - Nuwaysir, E F AU - Bittner, M AU - Trent, J AU - Barrett, J C AU - Afshari, CA AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, 111 Alexander Drive, Research Triangle Park, NC 27709, USA Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 153 EP - 159 VL - 24 IS - 3 SN - 0899-1987, 0899-1987 KW - Genetics Abstracts; Toxicology Abstracts KW - Reviews KW - Genetic analysis KW - Genotoxicity KW - Toxicology KW - G 07220:General theory/testing systems KW - X 24250:Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17236966?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+Carcinogenesis&rft.atitle=Microarrays+and+toxicology%3A+The+advent+of+toxicogenomics&rft.au=Nuwaysir%2C+E+F%3BBittner%2C+M%3BTrent%2C+J%3BBarrett%2C+J+C%3BAfshari%2C+CA&rft.aulast=Nuwaysir&rft.aufirst=E&rft.date=1999-03-01&rft.volume=24&rft.issue=3&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Molecular+Carcinogenesis&rft.issn=08991987&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Genotoxicity; Reviews; Toxicology; Genetic analysis ER - TY - JOUR T1 - An scFv phage clone that binds to human beta sub(2)-microglobulin AN - 17229172; 4509797 AB - Using phage display technology, a novel mouse scFv phage clone D1 was generated from mice immunized with single-chain HLA-A2, the human MHC class I molecules. D1 recognized a determinant in beta sub(2)-microglobulin. It reacted with beta sub(2)-microglobulin associated with the heavy chain of HLA-A2, recombinant beta sub(2)-microglobulin made in Escherichia coli or beta sub(2)-microglobulin prepared from human urine. The heavy chain variable region of D1 belongs to gene family VII and the light chain variable region belongs to the kappa chain gene family XI according to the Kabat database. JF - Immunotechnology AU - Jwang, Biru AU - Yerushalmi, N AU - Kreitman, R J AU - Engberg, J AU - Pastan, I AD - Laboratory of Molecular Biology, DBS, National Cancer Institute, National Institutes of Health, 37/4E16, 37 Convent Drive MSC 4255. Bethesda, MD 20892, USA Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 231 EP - 236 VL - 4 IS - 3-4 SN - 1380-2933, 1380-2933 KW - Fv KW - beta 2-microglobulin KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Phage display KW - Immunoglobulins KW - W3 33375:Antibodies KW - F 06711:Monoclonal antibodies, hybridomas, antigens and antisera KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17229172?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunotechnology&rft.atitle=An+scFv+phage+clone+that+binds+to+human+beta+sub%282%29-microglobulin&rft.au=Jwang%2C+Biru%3BYerushalmi%2C+N%3BKreitman%2C+R+J%3BEngberg%2C+J%3BPastan%2C+I&rft.aulast=Jwang&rft.aufirst=Biru&rft.date=1999-03-01&rft.volume=4&rft.issue=3-4&rft.spage=231&rft.isbn=&rft.btitle=&rft.title=Immunotechnology&rft.issn=13802933&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immunoglobulins; Phage display ER - TY - JOUR T1 - A New Era for Cancer Immunotherapy Based on the Genes that Encode Cancer Antigens AN - 17221444; 4507249 AB - In 1929, reviewing the available information concerning cancer immunotherapy, W. H. Woglom wrote, "It would be as difficult to reject the right ear and leave the left ear intact as it is to immunize against cancer" (1929). Minimal progress had been made since the earliest descriptions of attempts to immunize against cancer by Nooth, the surgeon to the Duke of Kent, who in 1777 inoculated himself with cancer tissue, or the physician to Louis XVIII, who in 1808 injected himself with breast cancer tissue. Knowledge of the cellular immune system was sparse, and as late as 1958 the Journal of Immunology did not list the word "lymphocyte" in its index. Most attempts to develop cancer vaccines involved immunization of cancer patients using either their own or allogeneic tumors along with a variety of nonspecific immune adjuvants. Even as the basic tenets of modern cellular immunology were elucidated, studies of cancer immunotherapy languished at the periphery of respectable science due to a lack of information regarding the molecular identification of the components of the putative immune reaction against human cancers. In the past decade, however, the convergence of information from basic studies of cellular and molecular immunology and the application of recombinant DNA techniques to produce pharmacologic quantities of biologic molecules normally present only in minute amounts have substantially changed views concerning the immune response to human cancer and have provided the first demonstrations that immune reactions against cancer antigens can lead to the regression of invasive tumors in selected patients. The molecular identification of tumor antigens, their immunodominant peptides, and the T cell receptors that recognize them have placed studies of tumor immunology and immunotherapy in the mainstream of immunologic research. JF - Immunity AU - Rosenberg, SA AD - Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA, sar@nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 281 EP - 287 VL - 10 IS - 3 SN - 1074-7613, 1074-7613 KW - Cancer patients KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Immunotherapy KW - Carcinoma KW - Reviews KW - Antigen (tumor-associated) KW - Vaccines KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - G 07439:General - reviews/ethics, etc. KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17221444?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunity&rft.atitle=A+New+Era+for+Cancer+Immunotherapy+Based+on+the+Genes+that+Encode+Cancer+Antigens&rft.au=Rosenberg%2C+SA&rft.aulast=Rosenberg&rft.aufirst=SA&rft.date=1999-03-01&rft.volume=10&rft.issue=3&rft.spage=281&rft.isbn=&rft.btitle=&rft.title=Immunity&rft.issn=10747613&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer patients; Carcinoma; Antigen (tumor-associated); Reviews; Vaccines; Immunotherapy ER - TY - JOUR T1 - Adeno-retroviral chimeric viruses as in vivo transducing agents AN - 17215841; 4493634 AB - Several hybrid viral gene transfer systems have been described that exploit the favorable features of the two parent viral species. We have developed a hybrid adeno-retroviral vector system to generate a retroviral vector in situ. The system consists of adenoviruses encoding MoMLV gag.pol (Axtet.gag.pol), the VSV-G viral envelope (Axtet.VSV-G), the retroviral vector LXSN expressing the neomycin phosphotransferase gene (AV-LXSN) and a transcriptional regulator to control expression of gag.pol and envelope (AV-rtTA). In vitro, biologically active retroviral vector preparations were generated following adeno-retroviral transduction of 9L rat glioma cells. In vivo the transcomplementing adeno-retroviruses were co-administered intratumorally into subcutaneous 9L glioma tumors in rats and human A375 melanoma xenografts in nude mice. In the 9L rat model, G418 super(R) cell cultures were only obtained when 9L cells were harvested from tumors injected with all four transcomplementing adeno-retroviruses. Molecular analysis of DNA extracted from 9L G418 super(R) populations derived both in vitro and in vivo showed appropriate integration of the LXSN proviral sequence. Tumor cells were harvested 1, 3 and 4 weeks after adeno-retrovirus administration to the human A375 xenografts. The percentage of G418 super(R) colonies recovered from tumors transduced with all of the transcomplementing adeno-retroviruses increased with time, whereas no increase was observed in tumors transduced with AV-LXSN alone. DNA extracted from G418 super(R) A375 cell populations showed the presence of integrated proviral sequences only in animals that received the full complement of adeno-retroviruses. These results demonstrate that adenoviral vectors expressing transcomplementing genes for retroviral proteins and retroviral vector RNAs can be used for in situ transduction of target cells. JF - Gene Therapy AU - Caplen, N J AU - Higginbotham, J N AU - Scheel, J R AU - Vahanian, N AU - Yoshida, Y AU - Hamada, H AU - Blaese, R M AU - Ramsey, W J AD - Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, 10C103, Bethesda, MD 20892, USA Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 454 EP - 459 VL - 6 IS - 3 SN - 0969-7128, 0969-7128 KW - adenovirus KW - mice KW - rats KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Tumors KW - Melanoma KW - Expression vectors KW - Retrovirus KW - Gene transfer KW - Glioma KW - W3 33181:Gene therapy vectors KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17215841?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Gene+Therapy&rft.atitle=Adeno-retroviral+chimeric+viruses+as+in+vivo+transducing+agents&rft.au=Caplen%2C+N+J%3BHigginbotham%2C+J+N%3BScheel%2C+J+R%3BVahanian%2C+N%3BYoshida%2C+Y%3BHamada%2C+H%3BBlaese%2C+R+M%3BRamsey%2C+W+J&rft.aulast=Caplen&rft.aufirst=N&rft.date=1999-03-01&rft.volume=6&rft.issue=3&rft.spage=454&rft.isbn=&rft.btitle=&rft.title=Gene+Therapy&rft.issn=09697128&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Glioma; Retrovirus; Gene transfer; Expression vectors; Tumors ER - TY - JOUR T1 - A live attenuated chimeric recombinant parainfluenza virus (PIV) encoding the internal proteins of PIV type 3 and the surface glycoproteins of PIV type 1 induces complete resistance to PIV1 challenge and partial resistance to PIV3 challenge AN - 17215296; 4499070 AB - The recovery of wild type and attenuated human parainfluenza type 3 (PIV3) recombinant viruses has made possible a new strategy to rapidly generate a live-attenuated vaccine virus for PIV1. We previously replaced the coding sequences for the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of PIV3 with those of PIV1 in the PIV3 antigenomic cDNA. This was used to recover a fully-viable, recombinant chimeric PIV3-PIV1 virus, termed rPIV3-1, which bears the major protective antigens of PIV1 and is wild type-like with regard to growth in cell culture and in hamsters. Here we report the recovery of a derivative of rPIV3-1 carrying the three temperature-sensitive and attenuating amino acid coding changes found in the L gene of the live-attenuated cp45 PIV3 candidate vaccine virus. This virus, termed rPIV3-1.cp45L, is temperature-sensitive with a shut-off temperature of 38 degree C, which is similar to that of the recombinant rPIV3cp45L, which possesses the same three mutations, rPIV3-1.cp45L is attenuated in the respiratory tract of hamsters to the same extent as rPIV3cp45L. Infection of hamsters with rPIV3-1.cp45L generated a moderate level of hemagglutination-inhibiting antibodies against wild type PIV1 and induced complete resistance to challenge with wild type PIV1. This demonstrates that this novel attenuated chimeric virus is capable of inducing a highly effective immune response against PIV1. It confirms previous observations that the surface glycoproteins of parainfluenza viruses are sufficient to induce a high level of resistance to homologous virus challenge. Unexpectedly, infection with recombinant chimeric virus rPIV3-1.cp45L or rPIV3-1, each bearing the surface glycoprotein genes of PIV1 and the internal genes of PIV3, also induced a moderate level of resistance to replication of wild type PIV3 challenge virus. This indicates that the internal genes of PIV3 can independently induce protective immunity against PIV3 in rodents, albeit a lower level of resistance than that induced by the surface glycoproteins. Thus, a reverse genetics system for PIV3 has been used successfully to produce a live attenuated PIV1 vaccine candidate that is attenuated and protective in experimental infection in hamsters. JF - Vaccine AU - Tao, T AU - Skiadopoulos, M H AU - Durbin, A P AU - Davoodi, F AU - Collins, P L AU - Murphy, B R AD - Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, & Center Drive, MSC 0720, Bethesda, MD 20892-0720, USA, ttao@atlas.niaid.nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 1100 EP - 1108 VL - 17 IS - 9-10 SN - 0264-410X, 0264-410X KW - double prime L gene KW - hamsters KW - human parainfluenza virus 3 KW - Microbiology Abstracts A: Industrial & Applied Microbiology; Virology & AIDS Abstracts; Immunology Abstracts KW - Temperature effects KW - Hemagglutinins KW - Vaccines KW - Glycoproteins KW - Human parainfluenza virus 3 KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - A 01097:Viruses UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17215296?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologya&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=A+live+attenuated+chimeric+recombinant+parainfluenza+virus+%28PIV%29+encoding+the+internal+proteins+of+PIV+type+3+and+the+surface+glycoproteins+of+PIV+type+1+induces+complete+resistance+to+PIV1+challenge+and+partial+resistance+to+PIV3+challenge&rft.au=Tao%2C+T%3BSkiadopoulos%2C+M+H%3BDurbin%2C+A+P%3BDavoodi%2C+F%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Tao&rft.aufirst=T&rft.date=1999-03-01&rft.volume=17&rft.issue=9-10&rft.spage=1100&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human parainfluenza virus 3; Hemagglutinins; Glycoproteins; Temperature effects; Vaccines ER - TY - JOUR T1 - Clearance of Chlamydia trachomatis from the Murine Genital Mucosa Does Not Require Perforin-Mediated Cytolysis or Fas-Mediated Apoptosis AN - 17204420; 4491255 AB - The molecular mechanisms of resistance to genital infection with the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis are unknown. A role for major histocompatibility complex class II-restricted, interleukin-12-dependent CD4 super(+) T cells has been established, but the functional activity of these cells does not depend on secretion of gamma interferon. Here we examined the potential contribution of T-cell-mediated cytotoxicity and apoptosis to mucosal clearance of MoPn by using mice deficient in the molecular mediators of target cell lysis. Animals lacking perforin, Fas, Fas ligand, or both perforin and Fas ligand were infected genitally with C. trachomatis MoPn and monitored for expression of immunity to chlamydial antigens and clearance of MoPn from the genital mucosa. In each case, the profile of spleen cytokine production, the magnitude of the host antibody response, and the kinetics of chlamydial clearance were similar to those of genetically intact controls. Compensatory overproduction of tumor necrosis factor alpha, an alternate mediator of apoptosis in certain cell types, did not appear to account for the ability of mutant mice to resolve Chlamydia infections. These results fail to support CD4 super(+) T-cell-mediated apoptosis or CD8 super(+) T-cell-mediated cytotoxicity as being critical to the clearance of C. trachomatis MoPn urogenital infections. JF - Infection and Immunity AU - Perry, L L AU - Feilzer, K AU - Hughes, S AU - Caldwell, H D AD - Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S. 4th St., Hamilton, MT 59840, USA, harlan_caldwell@nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 1379 EP - 1385 VL - 67 IS - 3 SN - 0019-9567, 0019-9567 KW - CD4 antigen KW - Chlamydia trachomatis KW - Fas antigen KW - mice KW - perforin KW - tumor necrosis factor- alpha KW - urogenital tract infection KW - Immunology Abstracts; Microbiology Abstracts B: Bacteriology KW - Interleukin 12 KW - Cytolysis KW - Major histocompatibility complex KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17204420?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Infection+and+Immunity&rft.atitle=Clearance+of+Chlamydia+trachomatis+from+the+Murine+Genital+Mucosa+Does+Not+Require+Perforin-Mediated+Cytolysis+or+Fas-Mediated+Apoptosis&rft.au=Perry%2C+L+L%3BFeilzer%2C+K%3BHughes%2C+S%3BCaldwell%2C+H+D&rft.aulast=Perry&rft.aufirst=L&rft.date=1999-03-01&rft.volume=67&rft.issue=3&rft.spage=1379&rft.isbn=&rft.btitle=&rft.title=Infection+and+Immunity&rft.issn=00199567&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Chlamydia trachomatis; Cytolysis; Major histocompatibility complex; Interleukin 12 ER - TY - JOUR T1 - No Discrepancy between in Vivo Gene Marking Efficiency Assessed in Peripheral Blood Populations Compared with Bone Marrow Progenitors or CD34 super(+) Cells AN - 17196084; 4487713 AB - Reports of 1- to 2-log higher gene transfer levels in purified CD34 super(+) cells or marrow CFU compared with levels in mature circulating blood cells after transplantation of retrovirally transduced primitive human hematopoietic cells have resulted in concern that transduced progenitors do not contribute proportionally to ongoing hematopoiesis (Kohn et al., 1995; Brenner, 1996). To study the issue in a relevant large animal, we analyzed samples of mature blood cells, marrow CD34-enriched cells and marrow CD34-depleted cells, and marrow CFU from a cohort of 11 rhesus transplanted with retrovirally transduced cells and followed for up to 5.5 years. They were transplanted with CD34-enriched bone marrow (BM) or G-CSF/SCF-mobilized peripheral blood (PB) cells transduced with vectors containing either neo, human glucocerebrosidase, or murine adenosine deaminase genes. There were no significant differences between the levels of vector sequences found in BM CD34 super(+) cells, BM CD34 super(-) cells, PB granulocytes, or PB mononuclear cells (MNCs) in any animal. In four animals transplanted with SCF/G-CSF-primed BM cells and analyzed 3-6 months posttransplantation, the percentage of CFU containing the neo vector appeared to be 1 log higher than the representation of marked cells in the PB of these animals, but this discrepancy did not persist at time points greater than 6 months post-transplantation. The level of CFU marking was no higher than PB granulocyte or MNC marking at any time points in the other animals. Low levels of mature gene-modified cells probably reflect poor transduction of repopulating stem cells, not a block in differentiation or specific immune rejection of mature cells. This study represents the longest follow-up of primates transplanted with transduced hematopoietic cells, and it is encouraging that the levels of vector-containing cells appear stable for up to 5 years. JF - Human Gene Therapy AU - Sellers, SE AU - Tisdale, J F AU - Bodine, D M AU - Williams, DA AU - Karlsson, S AU - Meztger, M AU - Donahue, R E AU - Dunbar, CE AD - Building 10, Room 7C103, Hematology Branch, NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA, dunbarc@gwgate.nhlbi.nih.gov Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 633 EP - 640 VL - 10 IS - 4 SN - 1043-0342, 1043-0342 KW - CD34 antigen KW - glucocerebrosidase KW - man KW - neo gene KW - rhesus monkeys KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Transplantation KW - Bone marrow KW - Gene transfer KW - Hemopoiesis KW - Blood cells KW - Adenosine deaminase KW - G 07240:Immunogenetics KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17196084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=No+Discrepancy+between+in+Vivo+Gene+Marking+Efficiency+Assessed+in+Peripheral+Blood+Populations+Compared+with+Bone+Marrow+Progenitors+or+CD34+super%28%2B%29+Cells&rft.au=Sellers%2C+SE%3BTisdale%2C+J+F%3BBodine%2C+D+M%3BWilliams%2C+DA%3BKarlsson%2C+S%3BMeztger%2C+M%3BDonahue%2C+R+E%3BDunbar%2C+CE&rft.aulast=Sellers&rft.aufirst=SE&rft.date=1999-03-01&rft.volume=10&rft.issue=4&rft.spage=633&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene transfer; Transplantation; Hemopoiesis; Bone marrow; Blood cells; Adenosine deaminase ER - TY - JOUR T1 - Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction AN - 17192405; 4488117 AB - Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI). We mutated two human ribonucleases--pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)--to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites. Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI. To elicit cellular targeting as well as to block RI binding, transferrin was conjugated to a mutant human RNase, rhRNase(Gly89 arrow right Cys) and a mutant EDN (Thr87 arrow right Cys). The transferrin-rhRNase(Gly89 arrow right Cys) thioether conjugate was 5000-fold more toxic to U251 cells than recombinant wild-type hRNase. In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase. Thus, we endowed two human RI-sensitive RNases with greater cytotoxicity by increasing their resistance to RI. This strategy has the potential to generate a novel set of recombinant human proteins useful for targeted therapy of cancer. JF - Nature Biotechnology AU - Suzuki, M AU - Saxena, S K AU - Boix, E AU - Prill, R J AU - Vasandani, V M AU - Ladner, JE AU - Sung, C AU - Youle, R J AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA, youle@helix.nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 265 EP - 270 VL - 17 IS - 3 SN - 1087-0156, 1087-0156 KW - eosinophil-derived neurotoxin KW - ribonuclease A KW - ribonuclease inhibitor KW - ribonuclease inhibitors KW - Biotechnology and Bioengineering Abstracts; Biochemistry Abstracts 2: Nucleic Acids; Medical and Pharmaceutical Biotechnology Abstracts KW - Antitumor agents KW - N 14711:RNases KW - W3 33374:Antitumor agents KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17192405?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Engineering+receptor-mediated+cytotoxicity+into+human+ribonucleases+by+steric+blockade+of+inhibitor+interaction&rft.au=Suzuki%2C+M%3BSaxena%2C+S+K%3BBoix%2C+E%3BPrill%2C+R+J%3BVasandani%2C+V+M%3BLadner%2C+JE%3BSung%2C+C%3BYoule%2C+R+J&rft.aulast=Suzuki&rft.aufirst=M&rft.date=1999-03-01&rft.volume=17&rft.issue=3&rft.spage=265&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antitumor agents ER - TY - JOUR T1 - Thymidine Kinase-Deleted Vaccinia Virus Expressing Purine Nucleoside Phosphorylase as a Vector for Tumor-Directed Gene Therapy AN - 17189427; 4487715 AB - Tumor-directed gene therapy faces many obstacles. Lack of tissue targeting and low in vivo transduction efficiency represent some of the limitations for a successful therapeutic outcome. A thymidine kinase-deleted mutant vaccinia virus has been shown in marker studies to replicate selectively in tumor tissue in animal models. Purine nucleoside phosphorylase (PNP), from E. coli, converts the nontoxic prodrug 6-methylpurine deoxyriboside (6-MPDR) to the toxic purine 6-methylpurine. In this study, we investigated the cytotoxic properties of PNP, expressed by an optimized synthetic early/late promoter in a vaccinia virus (vMPPNP). In vitro cytotoxicity of psoralen-inactivated vMPPNP (1 mu g of psoralen, 4 min of LWUV [365 nm]) at the maximum tolerated dose (MTD) of 6-MPDR (80 mu M) reduced cell viability by day 3 to 1.7%. At an MOI of 0.002, replication-competent vMPPNP and 6-MPDR (80 mu M) caused reduction of cell viability to 19.8% within 4 days. Furthermore, there was complete abrogation of viral replication after intracellular conversion of prodrug into the active toxin. The potency of such a system was similar among all histologies tested. Finally, the cytotoxic efficacy has been shown to be more rapid and complete than that of cytosine deaminase (CD), a more established enzyme/prodrug system. When virus was delivered intraperitoneally into athymic mice with hepatic metastases, followed by administration of prodrug, there was a significant prolongation of survival and a 30% cure rate. In summary, owing to its tumor-targeting capabilities, high transduction efficiency, and high gene expression, a vaccinia virus expressing PNP could prove to be a potent and valuable vector for tumor-targeted gene therapy. JF - Human Gene Therapy AU - Puhlmann, M AU - Gnant, M AU - Brown, C K AU - Alexander, H R AU - Bartlett, D L AD - Surgery Branch, National Cancer Institute, NIH Bldg. 10, Rm. 2B17, 10 Center Drive, Bethesda, MD 20892, USA, dbart@nih.gov Y1 - 1999/03/01/ PY - 1999 DA - 1999 Mar 01 SP - 649 EP - 657 VL - 10 IS - 4 SN - 1043-0342, 1043-0342 KW - 6-methylpurine KW - 6-methylpurine deoxyriboside KW - Vaccinia virus KW - mice KW - psoralen KW - Biotechnology and Bioengineering Abstracts; Genetics Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Purine-nucleoside phosphorylase KW - Gene therapy KW - Thymidine kinase KW - Tumors KW - Cytosine deaminase KW - G 07443:Gene therapy KW - W 30965:Miscellaneous, Reviews KW - W3 33180:Gene based (protocols, clinical trials, and animal models) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17189427?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Human+Gene+Therapy&rft.atitle=Thymidine+Kinase-Deleted+Vaccinia+Virus+Expressing+Purine+Nucleoside+Phosphorylase+as+a+Vector+for+Tumor-Directed+Gene+Therapy&rft.au=Puhlmann%2C+M%3BGnant%2C+M%3BBrown%2C+C+K%3BAlexander%2C+H+R%3BBartlett%2C+D+L&rft.aulast=Puhlmann&rft.aufirst=M&rft.date=1999-03-01&rft.volume=10&rft.issue=4&rft.spage=649&rft.isbn=&rft.btitle=&rft.title=Human+Gene+Therapy&rft.issn=10430342&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Purine-nucleoside phosphorylase; Gene therapy; Tumors; Cytosine deaminase; Thymidine kinase ER - TY - JOUR T1 - Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity AN - 17189330; 4488115 AB - We converted a model, syngeneic, nonimmunogenic tumor antigen into a vaccine by fusing it with a proinflammatory chemokine. Two chemokines, interferon inducible protein 10 and monocyte chemotactic protein 3, were fused to lymphoma Ig variable regions (sFv). The sFv-chemokine fusion proteins elicited chemotactic responses in vitro and induced inflammatory responses in vivo. Furthermore, in two independent models, vaccination with DNA constructs encoding the corresponding fusions generated superior protection against a large tumor challenge (20 times the minimum lethal dose), as compared with the best available protein vaccines. Immunity was not elicited by controls, including fusions with irrelevant sFv; fusions with a truncated chemokine that lacked receptor binding and chemotactic activity; mixtures of free chemokine and sFv proteins; or naked DNA plasmid vaccines encoding unlinked sFv and chemokine. The requirement for linkage of conformationally intact sFv and functionally active chemokine strongly suggested that the mechanism underlying these effects was the novel targeting of antigen presenting cells (APC) for chemokine receptor-mediated uptake of antigen, rather than the simple recruitment of APC to tumor by the chemokine. Finally, in addition to superior potency, these fusions were distinguished from lymphoma Ig fusions with granulocyte-macrophage colony-stimulating factor or other cytokines by their induction of critical effector T cells. JF - Nature Biotechnology AU - Biragyn, A AU - Tani, K AU - Grimm, M C AU - Weeks, S AU - Kwak, L W AD - Department of Experimental Transplantation and Immunology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA, kwak@mail.ncifcrf.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 253 EP - 258 VL - 17 IS - 3 SN - 1087-0156, 1087-0156 KW - Interferon inducible protein 10 KW - cancer vaccines KW - monocyte chemotactic protein 3 KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Chemokines KW - Immunotherapy KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Vaccines KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17189330?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Biotechnology&rft.atitle=Genetic+fusion+of+chemokines+to+a+self+tumor+antigen+induces+protective%2C+T-cell+dependent+antitumor+immunity&rft.au=Biragyn%2C+A%3BTani%2C+K%3BGrimm%2C+M+C%3BWeeks%2C+S%3BKwak%2C+L+W&rft.aulast=Biragyn&rft.aufirst=A&rft.date=1999-03-01&rft.volume=17&rft.issue=3&rft.spage=253&rft.isbn=&rft.btitle=&rft.title=Nature+Biotechnology&rft.issn=10870156&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Antigen (tumor-associated); Vaccines; Immunotherapy; Lymphocytes T; Chemokines ER - TY - JOUR T1 - Functional Analysis of the Active Partition Region of the Coxiella burnetii Plasmid QpH1 AN - 17178313; 4474022 AB - The partition region qsopAB of the Coxiella burnetii plasmid QpH1 was analyzed. Locus qsopA alone appears to fulfill the partitioning function; QsopA represses its own promoter 17-fold. Two partition-associated incompatibility sites were identified: incA in a 200-bp region covering the qsopA promoter and incB in the qsopB locus. JF - Journal of Bacteriology AU - Lin, Z AU - Mallavia, L P AD - Rm. 301, Molecular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, NIH, 5500 Nathan Shock Dr., Baltimore, MD 21224, zlin@intra.nida.nih.gov Y1 - 1999/03// PY - 1999 DA - Mar 1999 SP - 1947 EP - 1952 VL - 181 IS - 6 SN - 0021-9193, 0021-9193 KW - QsopA protein KW - incA gene KW - incB gene KW - plasmid QpH1 KW - qsopA gene KW - qsopB gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Coxiella burnetii KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17178313?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Bacteriology&rft.atitle=Functional+Analysis+of+the+Active+Partition+Region+of+the+Coxiella+burnetii+Plasmid+QpH1&rft.au=Lin%2C+Z%3BMallavia%2C+L+P&rft.aulast=Lin&rft.aufirst=Z&rft.date=1999-03-01&rft.volume=181&rft.issue=6&rft.spage=1947&rft.isbn=&rft.btitle=&rft.title=Journal+of+Bacteriology&rft.issn=00219193&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Coxiella burnetii ER - TY - JOUR T1 - The use of combination vaccinia vaccines and dual-gene vaccinia vaccines to enhance antigen-specific T-cell immunity via T-cell costimulation AN - 17193975; 4489136 AB - Several recombinant vaccinia viruses are currently being evaluated to induce antigen-specific immunity to a variety of infectious disease agents and tumor associated antigens. T-cell costimulation is extremely important in enhancing T-cell responses, and recombinant vaccines have now been shown to be effective vectors to express a range of these molecules. Both combination vaccines (an admixture of a recombinant vaccinia virus expressing a specific target antigen and a recombinant vaccinia virus expressing a costimulatory molecule) and dual-gene vaccines expressing both transgenes on the same vector have been shown capable of effectively enhancing antigen-specific responses via T-cell costimulation. In this report, we compare for the first time the use of both types of approaches to enhance antigen-specific T-cell responses, and we demonstrate the importance of route of vaccine administration and vaccine dose in attaining optimal T-cell responses. These studies should have direct bearing on the design of vaccine clinical trials for infectious agents and/or tumor associated antigens, in which T-cell costimulatory molecules will be employed to enhance antigen-specific T-cell responses via the use of either combination or dualgene vaccinia vaccines. JF - Vaccine AU - Kalus, R M AU - Kantor, JA AU - Gritz, L AU - Yafal, A G AU - Mazzara, G P AU - Schlom, J AU - Hodge, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA, js141c@nih.gov Y1 - 1999/02/26/ PY - 1999 DA - 1999 Feb 26 SP - 893 EP - 903 VL - 17 IS - 7-8 SN - 0264-410X, 0264-410X KW - man KW - vaccinia virus KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Vaccinia virus KW - Combined vaccines KW - Antigen (tumor-associated) KW - Lymphocytes T KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17193975?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Vaccine&rft.atitle=The+use+of+combination+vaccinia+vaccines+and+dual-gene+vaccinia+vaccines+to+enhance+antigen-specific+T-cell+immunity+via+T-cell+costimulation&rft.au=Kalus%2C+R+M%3BKantor%2C+JA%3BGritz%2C+L%3BYafal%2C+A+G%3BMazzara%2C+G+P%3BSchlom%2C+J%3BHodge%2C+J+W&rft.aulast=Kalus&rft.aufirst=R&rft.date=1999-02-26&rft.volume=17&rft.issue=7-8&rft.spage=893&rft.isbn=&rft.btitle=&rft.title=Vaccine&rft.issn=0264410X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Vaccinia virus; Antigen (tumor-associated); Vaccines; Lymphocytes T; Combined vaccines ER - TY - JOUR T1 - CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes. AN - 69666861; 10102627 AB - Previously, we have shown that nuclear extracts from cultured mouse keratinocytes induced to differentiate by increasing the levels of extra-cellular calcium contain Fra-1, Fra-2, Jun B, Jun D and c-Jun proteins that bind to the AP-1 DNA binding sequence. Despite this DNA binding activity, AP-1 reporter activity was suppressed in these cells. Here, we have detected the CREB family proteins CREB and CREMalpha as additional participants in the AP-1 DNA binding complex in differentiating keratinocytes. AP-1 and CRE DNA binding activity correlated with the induction of CREB, CREMalpha and ATF-1 and CREB phosphorylation at ser133 (ser133 phospho-CREB) in the transition from basal to differentiating keratinocytes, but the activity of a CRE reporter remained unchanged. In contrast, the CRE reporter was activated in the presence of the dominant-negative (DN) CREB mutants, KCREB and A-CREB, proteins that dimerize with CREB family members and block their ability to bind to DNA. The increase in CRE reporter activity in the presence of these mutants suggests that CRE-mediated transcriptional activity is suppressed in keratinocytes through protein-protein interactions involving a factor that dimerizes with the CREB leucine zipper. In experiments where the A-CREB mutant was co-transfected with an AP-1 reporter construct, transcriptional activity was also increased indicating that a CREB family member binds AP-1 sites and represses AP-1 transcriptional activity as well. Exogenous expression of the transcriptional repressor CREMalpha down-regulated both CRE and AP-1 reporters in keratinocytes suggesting that this factor may contribute to the suppression of AP-1 transcriptional activity observed in differentiating keratinocytes. JF - Oncogene AU - Rutberg, S E AU - Adams, T L AU - Olive, M AU - Alexander, N AU - Vinson, C AU - Yuspa, S H AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02/25/ PY - 1999 DA - 1999 Feb 25 SP - 1569 EP - 1579 VL - 18 IS - 8 SN - 0950-9232, 0950-9232 KW - Cyclic AMP Response Element-Binding Protein KW - 0 KW - DNA-Binding Proteins KW - Macromolecular Substances KW - Repressor Proteins KW - Transcription Factor AP-1 KW - Cyclic AMP Response Element Modulator KW - 135844-64-3 KW - DNA KW - 9007-49-2 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Animals KW - Phosphorylation KW - Transfection KW - Dimerization KW - Protein Processing, Post-Translational KW - Calcium -- physiology KW - Cell Differentiation KW - Mice KW - Protein Multimerization KW - Leucine Zippers KW - Binding Sites KW - Cyclic AMP Response Element-Binding Protein -- metabolism KW - Transcription, Genetic -- drug effects KW - Transcription Factor AP-1 -- antagonists & inhibitors KW - Transcription Factor AP-1 -- metabolism KW - DNA -- metabolism KW - DNA-Binding Proteins -- pharmacology KW - Keratinocytes -- metabolism KW - Cyclic AMP Response Element-Binding Protein -- pharmacology KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69666861?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Oncogene&rft.atitle=CRE+DNA+binding+proteins+bind+to+the+AP-1+target+sequence+and+suppress+AP-1+transcriptional+activity+in+mouse+keratinocytes.&rft.au=Rutberg%2C+S+E%3BAdams%2C+T+L%3BOlive%2C+M%3BAlexander%2C+N%3BVinson%2C+C%3BYuspa%2C+S+H&rft.aulast=Rutberg&rft.aufirst=S&rft.date=1999-02-25&rft.volume=18&rft.issue=8&rft.spage=1569&rft.isbn=&rft.btitle=&rft.title=Oncogene&rft.issn=09509232&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-22 N1 - Date created - 1999-04-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell cycle-related differences in susceptibility of NIH/3T3 cells to ribonucleases. AN - 69596544; 10047464 AB - Microinjection of Onconase or RNase A into NIH/3T3 cells was used to study the intracellular actions of these two proteins. Onconase preferentially killed actively growing cells in both microinjection and cell culture experiments. Moreover, agents that increased the number of cells in S phase such as serum or microinjected signal transduction mediators (Ras, protein kinase C, and mitogen-activated protein kinase) enhanced Onconase cytotoxicity. Conversely, agents that decreased these proliferative pathways (dibutyryl cAMP and protein kinase A) correspondingly diminished Onconase cytotoxicity in microinjection experiments. These results were also mimicked in cell culture experiments since log-phase v-ras-transformed NIH/3T3 cells were more sensitive to Onconase (IC50 of 7 microg/ml) than parental NIH/3T3 fibroblasts (IC50 of 40 microg/ml). Based on those data we postulated that Onconase-mediated cell death in NIH/3T3 cells was related to events occurring at two or more points in the cell cycle preferentially associated with late G1/S and S phases. In contrast, quiescent NIH/3T3 cells were more sensitive to microinjected RNase A than log phase cells and positive mediators of proliferative signal transduction did not enhance RNase A-mediated cytotoxicity. Taken together, these results demonstrate that these two RNases use different pathways and/or mechanisms to elicit cytotoxic responses in NIH/3T3 cells. Predictions formulated from these studies can be tested for relevance to RNase actions in different target tumor cells. Copyright 1999 Academic Press. JF - Experimental cell research AU - Smith, M R AU - Newton, D L AU - Mikulski, S M AU - Rybak, S M AD - Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA. Y1 - 1999/02/25/ PY - 1999 DA - 1999 Feb 25 SP - 220 EP - 232 VL - 247 IS - 1 SN - 0014-4827, 0014-4827 KW - Annexin A5 KW - 0 KW - Culture Media, Conditioned KW - Culture Media, Serum-Free KW - Egg Proteins KW - Ribonucleases KW - EC 3.1.- KW - Ribonuclease, Pancreatic KW - EC 3.1.27.5 KW - Oncogene Protein p21(ras) KW - EC 3.6.5.2 KW - ranpirnase KW - ZE15FIT23E KW - Index Medicus KW - Animals KW - Ribonuclease, Pancreatic -- toxicity KW - Interphase -- drug effects KW - Mice KW - Microinjections KW - Annexin A5 -- pharmacology KW - Cell Death -- drug effects KW - Cattle KW - Cell Line, Transformed KW - Egg Proteins -- toxicity KW - Extracellular Space -- enzymology KW - Oncogene Protein p21(ras) -- physiology KW - Drug Synergism KW - Cell Transformation, Viral KW - Ribonucleases -- toxicity KW - 3T3 Cells -- drug effects KW - 3T3 Cells -- enzymology KW - Cell Cycle -- drug effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69596544?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Experimental+cell+research&rft.atitle=Cell+cycle-related+differences+in+susceptibility+of+NIH%2F3T3+cells+to+ribonucleases.&rft.au=Smith%2C+M+R%3BNewton%2C+D+L%3BMikulski%2C+S+M%3BRybak%2C+S+M&rft.aulast=Smith&rft.aufirst=M&rft.date=1999-02-25&rft.volume=247&rft.issue=1&rft.spage=220&rft.isbn=&rft.btitle=&rft.title=Experimental+cell+research&rft.issn=00144827&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-17 N1 - Date created - 1999-03-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Activation of nuclear factor of activated T cells-(NFAT) and activating protein 1 (AP-1) by oncogenic 70Z Cbl requires an intact phosphotyrosine binding domain but not Crk(L) or p85 phosphatidylinositol 3-kinase association. AN - 69576124; 9988765 AB - The Cbl proto-oncogene product is a complex adapter protein that functions as a negative regulator of protein tyrosine kinases. It is rapidly tyrosine-phosphorylated and associates with Crk(L) and p85 phosphatidylinositol 3-kinase (PI3K) upon engagement of numerous receptors linked to tyrosine kinases. Elucidation of the mechanism(s) underlying Cbl deregulation is therefore of considerable interest. The 70Z Cbl oncoprotein shows increased baseline tyrosine phosphorylation in fibroblasts and enhances nuclear factor of activated T cells (NFAT) activity in Jurkat T cells. Its transforming ability has been proposed to relate to its increased phosphotyrosine content. We demonstrate that 70Z Cbl shows increased basal and activation-induced tyrosine phosphorylation and association with Crk(L) and p85 PI3K in Jurkat T cells. 70Z Cbl, however, retains the ability to enhance NFAT and activating protein 1 (AP1) activity in the absence of Crk(L)/p85 PI3K association. In contrast, the G306E mutation, which inactivates the phosphotyrosine binding domain of Cbl, blocks NFAT/AP1 activation by 70Z Cbl. We conclude that 70Z Cbl-induced NFAT/AP1 activation requires the phosphotyrosine binding domain but not Crk(L)/p85 PI3K association. We hypothesize that 70Z Cbl acts as a dominant negative by blocking the negative regulatory function of the Cbl phosphotyrosine binding domain on protein-tyrosine kinases. JF - The Journal of biological chemistry AU - van Leeuwen, J E AU - Paik, P K AU - Samelson, L E AD - Cell Biology and Metabolism Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA. vanleeuj@box-v.nih.gov Y1 - 1999/02/19/ PY - 1999 DA - 1999 Feb 19 SP - 5153 EP - 5162 VL - 274 IS - 8 SN - 0021-9258, 0021-9258 KW - Adaptor Proteins, Signal Transducing KW - 0 KW - CRKL protein KW - DNA-Binding Proteins KW - NFATC Transcription Factors KW - Nuclear Proteins KW - Oncogene Protein v-cbl KW - Retroviridae Proteins, Oncogenic KW - Transcription Factor AP-1 KW - Transcription Factors KW - Phosphotyrosine KW - 21820-51-9 KW - Tyrosine KW - 42HK56048U KW - Phosphatidylinositol 3-Kinases KW - EC 2.7.1.- KW - Calcium-Calmodulin-Dependent Protein Kinases KW - EC 2.7.11.17 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Calcium-Calmodulin-Dependent Protein Kinases -- metabolism KW - Base Sequence KW - Phosphorylation KW - Humans KW - Jurkat Cells KW - Tyrosine -- metabolism KW - Protein Binding KW - Retroviridae Proteins, Oncogenic -- genetics KW - Phosphatidylinositol 3-Kinases -- metabolism KW - Transcription Factors -- metabolism KW - Transcription Factor AP-1 -- metabolism KW - Phosphotyrosine -- metabolism KW - Nuclear Proteins -- metabolism KW - Retroviridae Proteins, Oncogenic -- metabolism KW - DNA-Binding Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69576124?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Activation+of+nuclear+factor+of+activated+T+cells-%28NFAT%29+and+activating+protein+1+%28AP-1%29+by+oncogenic+70Z+Cbl+requires+an+intact+phosphotyrosine+binding+domain+but+not+Crk%28L%29+or+p85+phosphatidylinositol+3-kinase+association.&rft.au=van+Leeuwen%2C+J+E%3BPaik%2C+P+K%3BSamelson%2C+L+E&rft.aulast=van+Leeuwen&rft.aufirst=J&rft.date=1999-02-19&rft.volume=274&rft.issue=8&rft.spage=5153&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-18 N1 - Date created - 1999-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mutagenesis of the conserved residue Glu259 of Gsalpha demonstrates the importance of interactions between switches 2 and 3 for activation. AN - 69574720; 9988742 AB - We previously reported that substitution of Arg258 within the switch 3 region of Gsalpha impaired activation and increased basal GDP release due to loss of an interaction between the helical and GTPase domains (Warner, D. R., Weng, G., Yu, S., Matalon, R., and Weinstein, L. S. (1998) J Biol. Chem. 273, 23976-23983). The adjacent residue (Glu259) is strictly conserved in G protein alpha-subunits and is predicted to be important in activation. To determine the importance of Glu259, this residue was mutated to Ala (Gsalpha-E259A), Gln (Gsalpha-E259Q), Asp (Gsalpha-E259D), or Val (Gsalpha-E259V), and the properties of in vitro translation products were examined. The Gsalpha-E259V was studied because this mutation was identified in a patient with Albright hereditary osteodystrophy. S49 cyc reconstitution assays demonstrated that Gsalpha-E259D stimulated adenylyl cyclase normally in the presence of GTPgammaS but was less efficient with isoproterenol or AlF4-. The other mutants had more severely impaired effector activation, particularly in response to AlF4-. In trypsin protection assays, GTPgammaS was a more effective activator than AlF4- for all mutants, with Gsalpha-E259D being the least severely impaired. For Gsalpha-E259D, the AlF4--induced activation defect was more pronounced at low Mg2+ concentrations. Gsalpha-E259D and Gsalpha-E259A purified from Escherichia coli had normal rates of GDP release (as assessed by the rate GTPgammaS binding). However, for both mutants, the ability of AlF4- to decrease the rate of GTPgammaS binding was impaired, suggesting that they bound AlF4- more poorly. GTPgammaS bound to purified Gsalpha-E259D irreversibly in the presence of 1 mM free Mg2+, but dissociated readily at micromolar concentrations. Sucrose density gradient analysis of in vitro translates demonstrated that all mutants except Gsalpha-E259V bind to beta gamma at 0 degreesC and were stable at higher temperatures. In the active conformation Glu259 interacts with conserved residues in the switch 2 region that are important in maintaining both the active state and AlF4- in the guanine nucleotide binding pocket. Although both Gsalpha Arg258 and Glu259 are critical for activation, the mechanisms by which these residues affect Gsalpha protein activation are distinct. JF - The Journal of biological chemistry AU - Warner, D R AU - Romanowski, R AU - Yu, S AU - Weinstein, L S AD - Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, NINDS, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA. dwarner@helix.nih.gov Y1 - 1999/02/19/ PY - 1999 DA - 1999 Feb 19 SP - 4977 EP - 4984 VL - 274 IS - 8 SN - 0021-9258, 0021-9258 KW - Aluminum Compounds KW - 0 KW - DNA Primers KW - Recombinant Proteins KW - Guanosine Diphosphate KW - 146-91-8 KW - Guanosine 5'-O-(3-Thiotriphosphate) KW - 37589-80-3 KW - Glutamic Acid KW - 3KX376GY7L KW - GTP-Binding Protein alpha Subunits, Gs KW - EC 3.6.5.1 KW - Magnesium KW - I38ZP9992A KW - Fluorides KW - Q80VPU408O KW - aluminum fluoride KW - Z77H3IKW94 KW - Index Medicus KW - Animals KW - Fluorides -- metabolism KW - Guanosine Diphosphate -- metabolism KW - Recombinant Proteins -- genetics KW - Protein Binding KW - Magnesium -- metabolism KW - Mutagenesis, Site-Directed KW - Base Sequence KW - Cattle KW - Conserved Sequence KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Guanosine 5'-O-(3-Thiotriphosphate) -- metabolism KW - Recombinant Proteins -- chemistry KW - Protein Conformation KW - Aluminum Compounds -- metabolism KW - Glutamic Acid -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- genetics KW - Glutamic Acid -- chemistry KW - GTP-Binding Protein alpha Subunits, Gs -- metabolism KW - GTP-Binding Protein alpha Subunits, Gs -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69574720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Mutagenesis+of+the+conserved+residue+Glu259+of+Gsalpha+demonstrates+the+importance+of+interactions+between+switches+2+and+3+for+activation.&rft.au=Warner%2C+D+R%3BRomanowski%2C+R%3BYu%2C+S%3BWeinstein%2C+L+S&rft.aulast=Warner&rft.aufirst=D&rft.date=1999-02-19&rft.volume=274&rft.issue=8&rft.spage=4977&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-18 N1 - Date created - 1999-03-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Targeted disruption of gene function in Drosophila by RNA interference (RNA-i): a role for nautilus in embryonic somatic muscle formation. AN - 69584317; 9990044 AB - The expression of the MyoD gene homolog, nautilus (nau), in the Drosophila embryo defines a subset of mesodermal cells known as the muscle "pioneer" or "founder" cells. These cells are thought to establish the future muscle pattern in each hemisegment. Founders appear to recruit fusion-competent mesodermal cells to establish a particular muscle fiber type. In support of this concept every somatic muscle in the embryo is associated with one or more nautilus-positive cells. However, because of the lack of known (isolated) nautilus mutations, no direct test of the founder cell hypothesis has been possible. We now have utilized toxin ablation and genetic interference by double-stranded RNA (RNA interference or RNA-i) to determine both the role of the nautilus-expressing cells and the nautilus gene, respectively, in embryonic muscle formation. In the absence of nautilus-expressing cells muscle formation is severely disrupted or absent. A similar phenotype is observed with the elimination of the nautilus gene product by genetic interference upon injection of nautilus double-stranded RNA. These results define a crucial role for nautilus in embryonic muscle formation. The application of RNA interference to a variety of known Drosophila mutations as controls gave phenotypes essentially indistinguishable from the original mutation. RNA-i provides a powerful approach for the targeted disruption of a given genetic function in Drosophila. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Misquitta, L AU - Paterson, B M AD - Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02/16/ PY - 1999 DA - 1999 Feb 16 SP - 1451 EP - 1456 VL - 96 IS - 4 SN - 0027-8424, 0027-8424 KW - Drosophila Proteins KW - 0 KW - Insect Proteins KW - Muscle Proteins KW - RNA, Antisense KW - RNA, Double-Stranded KW - Transcription Factors KW - nautilus protein, Drosophila KW - 134548-65-5 KW - Index Medicus KW - Phenotype KW - Embryonic Induction KW - Animals KW - RNA, Double-Stranded -- genetics KW - Embryo, Nonmammalian -- physiology KW - Larva KW - Embryo, Nonmammalian -- drug effects KW - Chorion KW - Female KW - Mutagenesis KW - Insect Proteins -- genetics KW - RNA, Antisense -- pharmacology KW - Muscles -- embryology KW - Drosophila -- genetics KW - Gene Expression Regulation, Developmental KW - Drosophila -- embryology KW - Insect Proteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69584317?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Targeted+disruption+of+gene+function+in+Drosophila+by+RNA+interference+%28RNA-i%29%3A+a+role+for+nautilus+in+embryonic+somatic+muscle+formation.&rft.au=Misquitta%2C+L%3BPaterson%2C+B+M&rft.aulast=Misquitta&rft.aufirst=L&rft.date=1999-02-16&rft.volume=96&rft.issue=4&rft.spage=1451&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Nature. 1983 Jan 6;301(5895):66-9 [6337338] Cell. 1998 Dec 23;95(7):1017-26 [9875855] Biotechnology. 1988;10:437-56 [2850048] Genes Dev. 1988 Jul;2(7):843-52 [3209070] Genes Dev. 1988 Dec;2(12A):1666-76 [2850968] Mol Cell Biol. 1989 Oct;9(10):4304-11 [2573829] Genes Dev. 1990 Dec;4(12A):2098-111 [1980118] Development. 1990 Nov;110(3):791-804 [2100994] Proc Natl Acad Sci U S A. 1991 May 1;88(9):3782-6 [1902570] Development. 1993 Jun;118(2):401-15 [8223268] Cell. 1993 Dec 31;75(7):1241-4 [8269506] Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5662-6 [8202544] Development. 1994 Jun;120(6):1631-41 [8050369] Science. 1995 Feb 3;267(5198):688-93 [7839146] Trends Genet. 1995 Apr;11(4):153-9 [7732594] Bioessays. 1995 Mar;17(3):203-9 [7748174] Development. 1995 Jul;121(7):1979-88 [7635046] Development. 1995 Nov;121(11):3703-12 [8582282] Dev Biol. 1997 Jan 15;181(2):197-212 [9013930] Development. 1997 Sep;124(17):3253-62 [9310320] Curr Top Dev Biol. 1998;38:35-80 [9399076] Nature. 1998 Feb 19;391(6669):806-11 [9486653] Development. 1998 Jun;125(11):2075-86 [9570772] Dev Biol. 1998 Oct 15;202(2):153-6 [9769168] EMBO J. 1988 Jul;7(7):2175-83 [3416836] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice. AN - 69583915; 9990086 AB - Members of the muscarinic acetylcholine receptor family (M1-M5) are known to be involved in a great number of important central and peripheral physiological and pathophysiological processes. Because of the overlapping expression patterns of the M1-M5 muscarinic receptor subtypes and the lack of ligands endowed with sufficient subtype selectivity, the precise physiological functions of the individual receptor subtypes remain to be elucidated. To explore the physiological roles of the M2 muscarinic receptor, we have generated mice lacking functional M2 receptors by using targeted mutagenesis in mouse embryonic stem cells. The resulting mutant mice were analyzed in several behavioral and pharmacologic tests. These studies showed that the M2 muscarinic receptor subtype, besides its well documented involvement in the regulation of heart rate, plays a key role in mediating muscarinic receptor-dependent movement and temperature control as well as antinociceptive responses, three of the most prominent central muscarinic effects. These results offer a rational basis for the development of novel muscarinic drugs. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Gomeza, J AU - Shannon, H AU - Kostenis, E AU - Felder, C AU - Zhang, L AU - Brodkin, J AU - Grinberg, A AU - Sheng, H AU - Wess, J AD - Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA. Y1 - 1999/02/16/ PY - 1999 DA - 1999 Feb 16 SP - 1692 EP - 1697 VL - 96 IS - 4 SN - 0027-8424, 0027-8424 KW - Receptor, Muscarinic M2 KW - 0 KW - Receptors, Muscarinic KW - Oxotremorine KW - 5RY0UWH1JL KW - Morphine KW - 76I7G6D29C KW - Index Medicus KW - Animals KW - Pain -- physiopathology KW - Homozygote KW - Salivation -- drug effects KW - Salivation -- genetics KW - Gene Expression KW - Organ Specificity KW - Mice KW - Genomic Library KW - Salivation -- physiology KW - Mice, Knockout KW - Morphine -- pharmacology KW - Mutagenesis, Site-Directed KW - Analgesia KW - In Situ Hybridization KW - Restriction Mapping KW - Pain -- genetics KW - Stem Cells KW - Embryo, Mammalian KW - Female KW - Male KW - Tremor -- physiopathology KW - Tremor -- genetics KW - Receptors, Muscarinic -- genetics KW - Oxotremorine -- pharmacology KW - Brain -- metabolism KW - Receptors, Muscarinic -- physiology KW - Receptors, Muscarinic -- deficiency UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69583915?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=Pronounced+pharmacologic+deficits+in+M2+muscarinic+acetylcholine+receptor+knockout+mice.&rft.au=Gomeza%2C+J%3BShannon%2C+H%3BKostenis%2C+E%3BFelder%2C+C%3BZhang%2C+L%3BBrodkin%2C+J%3BGrinberg%2C+A%3BSheng%2C+H%3BWess%2C+J&rft.aulast=Gomeza&rft.aufirst=J&rft.date=1999-02-16&rft.volume=96&rft.issue=4&rft.spage=1692&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Trends Pharmacol Sci. 1989 Dec;Suppl:75-9 [2694528] Exp Neurol. 1966 Mar;14(3):371-82 [4951849] J Pharmacol Exp Ther. 1991 Feb;256(2):727-33 [1994002] J Neurosci. 1991 Oct;11(10):3218-26 [1941081] Mol Pharmacol. 1993 Feb;43(2):149-57 [8429821] Life Sci. 1993;52(5-6):441-8 [8441326] J Pharmacol Exp Ther. 1993 Jul;266(1):329-38 [8101218] Pharmacol Toxicol. 1993 Apr-May;72(4-5):262-7 [8372044] Pharmacol Ther. 1993 Jun;58(3):319-79 [7504306] Prog Brain Res. 1993;98:95-101 [8248542] J Neurosci. 1994 May;14(5 Pt 2):3351-63 [8182478] Ann N Y Acad Sci. 1995 May 10;757:186-93 [7611674] Nat Genet. 1995 Sep;11(1):33-9 [7550311] J Neurosci. 1995 Dec;15(12):8167-76 [8613751] Nature. 1996 Oct 10;383(6600):535-8 [8849726] Crit Rev Neurobiol. 1996;10(1):69-99 [8853955] Life Sci. 1997;60(13-14):969-76 [9121363] J Pharmacol Exp Ther. 1997 Apr;281(1):470-7 [9103533] J Pharmacol Exp Ther. 1997 May;281(2):876-83 [9152397] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13311-6 [9371842] Life Sci. 1962 Aug;1:361-3 [13947224] Annu Rev Pharmacol Toxicol. 1990;30:633-73 [2188581] Int J Neuropharmacol. 1966 May;5(3):207-16 [5916121] Eur J Pharmacol. 1973 Mar;21(3):337-42 [4736076] Neuropharmacology. 1979 Jul;18(7):601-3 [573869] Eur J Pharmacol. 1983 Nov 25;95(3-4):193-8 [6653670] Life Sci. 1985 May 27;36(21):2007-15 [4039782] Eur J Pharmacol. 1985 Oct 29;117(1):81-8 [3841316] Prog Neurobiol. 1986;26(2):119-46 [3704168] J Pharmacol Exp Ther. 1987 Feb;240(2):370-5 [3806401] J Med Chem. 1988 Jan;31(1):160-4 [3336014] J Neurosci. 1988 Dec;8(12):4646-52 [3199198] Comment In: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12222-3 [10535900] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The [URE3] prion is an aggregated form of Ure2p that can be cured by overexpression of Ure2p fragments. AN - 69581664; 9990052 AB - The [URE3] nonchromosomal genetic element is a prion of Ure2p, a regulator of nitrogen catabolism in Saccharomyces cerevisiae. Ure2p1-65 is the prion domain of Ure2p, sufficient to propagate [URE3] in vivo. We show that full length Ure2p-green fluorescent protein (GFP) or a Ure2p1-65-GFP fusion protein is aggregated in cells carrying [URE3] but is evenly distributed in cells lacking the [URE3] prion. This indicates that [URE3] involves a self-propagating aggregation of Ure2p. Overexpression of Ure2p1-65 induces the de novo appearance of [URE3] by 1,000-fold in a strain initially [ure-o], but cures [URE3] from a strain initially carrying the [URE3] prion. Overexpression of several other fragments of Ure2p or Ure2-GFP fusion proteins also efficiently cures the prion. We suggest that incorporation of fragments or fusion proteins into a putative [URE3] "crystal" of Ure2p poisons its propagation. JF - Proceedings of the National Academy of Sciences of the United States of America AU - Edskes, H K AU - Gray, V T AU - Wickner, R B AD - Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA. Y1 - 1999/02/16/ PY - 1999 DA - 1999 Feb 16 SP - 1498 EP - 1503 VL - 96 IS - 4 SN - 0027-8424, 0027-8424 KW - Fungal Proteins KW - 0 KW - Luminescent Proteins KW - Prions KW - Recombinant Fusion Proteins KW - Repressor Proteins KW - Saccharomyces cerevisiae Proteins KW - Green Fluorescent Proteins KW - 147336-22-9 KW - Glutathione Peroxidase KW - EC 1.11.1.9 KW - URE2 protein, S cerevisiae KW - Nitrogen KW - N762921K75 KW - Index Medicus KW - Repressor Proteins -- biosynthesis KW - Recombinant Fusion Proteins -- biosynthesis KW - Genetic Complementation Test KW - Plasmids KW - Repressor Proteins -- genetics KW - Nitrogen -- metabolism KW - Luminescent Proteins -- genetics KW - Luminescent Proteins -- biosynthesis KW - Saccharomyces cerevisiae -- genetics KW - Prions -- genetics KW - Prions -- chemistry KW - Saccharomyces cerevisiae -- metabolism KW - Fungal Proteins -- biosynthesis KW - Fungal Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69581664?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.atitle=The+%5BURE3%5D+prion+is+an+aggregated+form+of+Ure2p+that+can+be+cured+by+overexpression+of+Ure2p+fragments.&rft.au=Edskes%2C+H+K%3BGray%2C+V+T%3BWickner%2C+R+B&rft.aulast=Edskes&rft.aufirst=H&rft.date=1999-02-16&rft.volume=96&rft.issue=4&rft.spage=1498&rft.isbn=&rft.btitle=&rft.title=Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America&rft.issn=00278424&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Bacteriol. 1988 Feb;170(2):708-13 [2892826] Gene. 1987;52(2-3):225-33 [3038686] Nature. 1989 Mar 23;338(6213):342-5 [2564168] Microbiology. 1997 Feb;143 ( Pt 2):303-11 [9043107] Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12503-8 [9356479] J Biol Chem. 1998 Oct 30;273(44):28912-20 [9786894] Mol Gen Genet. 1975;136(4):327-35 [16095000] Genetics. 1989 May;122(1):19-27 [2659436] Cell. 1990 Nov 16;63(4):673-86 [1977523] Mol Cell Biol. 1991 Feb;11(2):822-32 [1990286] Gene. 1992 Jan 2;110(1):119-22 [1544568] Cell. 1993 Jul 2;73(7):1339-47 [8100741] Curr Genet. 1993 Sep;24(3):268-70 [8221937] Science. 1994 Apr 22;264(5158):566-9 [7909170] Nature. 1994 Aug 11;370(6489):471-4 [7913989] Genetics. 1994 Jul;137(3):659-70 [8088511] Genetics. 1994 Jul;137(3):671-6 [8088512] Science. 1995 May 12;268(5212):880-4 [7754373] Science. 1995 Oct 6;270(5233):93-5 [7569955] EMBO J. 1996 Jun 17;15(12):3127-34 [8670813] Science. 1996 Aug 2;273(5275):622-6 [8662547] J Bacteriol. 1996 Aug;178(15):4734-6 [8755910] Nature. 1967 May 20;214(5090):764-6 [4963878] Nature. 1967 Sep 2;215(5105):1043-4 [4964084] J Comp Pathol. 1968 Jul;78(3):293-9 [4970191] J Bacteriol. 1971 May;106(2):519-22 [5573734] Acta Neuropathol. 1981;54(1):63-74 [7195134] Genet Res. 1981 Apr;37(2):173-82 [7021322] Science. 1982 Dec 24;218(4579):1309-11 [6815801] Cell. 1983 Dec;35(2 Pt 1):349-58 [6418385] Cell. 1985 Apr;40(4):735-46 [2859120] Nature. 1985 May 23-29;315(6017):331-3 [3923361] J Bacteriol. 1987 Jun;169(6):2598-600 [3294799] Yeast. 1988 Sep;4(3):159-78 [3059716] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cell biology of the hippocampal formation in schizophrenia. AN - 69615029; 10071707 AB - The hippocampal formation (HF) has been a centerpiece of neuropathologic investigations of schizophrenia. Numerous MRI studies have demonstrated a slight bilateral reduction in HF volume. Reports of reduced N-acetyl aspartate measured with in vivo proton spectroscopy suggest that neuronal pathology exists. However, morphometric data from postmortem studies have not revealed a clear change in HF size, and recent studies of neuronal number and of cytoarchitecture have been largely negative. Evidence of glial proliferation is consistently absent. The most reproducible positive anatomic finding in postmortem HF has been reduced size of neuronal cell bodies. Studies of gene transcription have provided replicable evidence of decreased expression of mRNAs for synaptophysin, GAP-43, cholecystokinin, and non-NMDA glutamate receptor subunits (GLU R 1 and 2), particularly in CA 3-4. These data about the cellular and molecular biology of the HF in schizophrenia are different from that found in a number of conditions associated with hippocampal damage, including excitotoxicity, epilepsy, alcoholism, Alzheimer's disease, steroid neurotoxicity, and normal aging. Notwithstanding the real possibility that the data are epiphenomena of chronic illness, the findings may implicate a unique cellular defect in schizophrenia--a genetic variation affecting the plasticity of HF circuitry and connectivity. Directions for further research are proposed. JF - Biological psychiatry AU - Weinberger, D R AD - Clinical Brain Disorders Branch Intramural Research Program, National Institute Of Mental Health, NIH, Bethesda, Maryland 20892, USA. Y1 - 1999/02/15/ PY - 1999 DA - 1999 Feb 15 SP - 395 EP - 402 VL - 45 IS - 4 SN - 0006-3223, 0006-3223 KW - Nerve Tissue Proteins KW - 0 KW - Index Medicus KW - Phenotype KW - Neural Pathways -- physiopathology KW - Humans KW - Neuronal Plasticity -- physiology KW - Nerve Tissue Proteins -- metabolism KW - Transcription, Genetic KW - Neural Pathways -- pathology KW - Nerve Tissue Proteins -- genetics KW - Neurons -- metabolism KW - Schizophrenia -- metabolism KW - Hippocampus -- metabolism KW - Hippocampus -- pathology KW - Schizophrenia -- pathology KW - Schizophrenia -- genetics KW - Neurons -- pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69615029?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biological+psychiatry&rft.atitle=Cell+biology+of+the+hippocampal+formation+in+schizophrenia.&rft.au=Weinberger%2C+D+R&rft.aulast=Weinberger&rft.aufirst=D&rft.date=1999-02-15&rft.volume=45&rft.issue=4&rft.spage=395&rft.isbn=&rft.btitle=&rft.title=Biological+psychiatry&rft.issn=00063223&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-13 N1 - Date created - 1999-05-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. AN - 69591759; 10029071 AB - Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We report here the cloning and characterization of the 5'-regulatory region of the hTERT gene. The highly GC-rich content of the 5' end of the hTERT cDNA spans to the 5'-flanking region and intron 1, making a CpG island. A 1.7-kb DNA fragment encompassing the hTERT gene promoter was placed upstream of the luciferase reporter gene and transiently transfected into human cell lines of fibroblastic and epithelial origins that differed in their expression of the endogenous hTERT gene. Endogenous hTERT-expressing cells, but not nonexpressing cells, showed high levels of luciferase activity, suggesting that the regulation of hTERT gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments revealed that a 59-bp region (-208 to -150) is required for the maximal promoter activity. The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase activation. Identification of the regulatory regions of the hTERT promoter sequence will be essential in understanding the molecular mechanisms of positive and negative regulation of telomerase. JF - Cancer research AU - Horikawa, I AU - Cable, P L AU - Afshari, C AU - Barrett, J C AD - Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/02/15/ PY - 1999 DA - 1999 Feb 15 SP - 826 EP - 830 VL - 59 IS - 4 SN - 0008-5472, 0008-5472 KW - DNA-Binding Proteins KW - 0 KW - Proteins KW - telomerase RNA KW - RNA KW - 63231-63-0 KW - Telomerase KW - EC 2.7.7.49 KW - Index Medicus KW - Base Sequence KW - Humans KW - Molecular Sequence Data KW - Transcription, Genetic KW - Hepatitis B virus -- genetics KW - Virus Integration KW - Cloning, Molecular KW - Promoter Regions, Genetic KW - Telomerase -- genetics KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69591759?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Cloning+and+characterization+of+the+promoter+region+of+human+telomerase+reverse+transcriptase+gene.&rft.au=Horikawa%2C+I%3BCable%2C+P+L%3BAfshari%2C+C%3BBarrett%2C+J+C&rft.aulast=Horikawa&rft.aufirst=I&rft.date=1999-02-15&rft.volume=59&rft.issue=4&rft.spage=826&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-04 N1 - Date created - 1999-03-04 N1 - Date revised - 2017-01-13 N1 - Genetic sequence - AF098956; GENBANK N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - COOH-terminal domain of p53 modulates p53-mediated transcriptional transactivation, cell growth, and apoptosis. AN - 69589198; 10029073 AB - The tumor suppressor protein p53 contributes to the control of cell cycle checkpoints and stress-induced apoptosis and is frequently mutated in many different types of human cancers. The COOH terminus of p53 modulates the transcriptional and apoptotic activities of the protein. Although COOH-terminal mutants of p53 are uncommon, we proposed that these p53 mutants nevertheless contributed to the selective clonal expansion of the cancer cells. Therefore, we analyzed the tumor-derived p53 COOH-terminal domain (CTD) mutants (352D/H, 356G/W, 342-stop, 360-del, and 387-del) functionally. The results have revealed that all mutants have impaired apoptotic activity when compared with wild-type p53. However, some of these mutants still transcriptionally transactivate p21Waf/Cip1 and inhibit cell growth. Interestingly, of the tumor-derived CTD mutants, oligomerization-defective mutant 342-stop was the only one that did not exhibit sequence-specific DNA binding or failed to transactivate p21Waf1/Cip1, Bax, and IGF-BP3 transcriptionally. The failure to inhibit cell growth by this tumor-derived CTD mutant supports the hypothesis that p53 sequence-specific transcriptional transactivity to p21Waf1/Cip1 is correlated with induction of cell cycle arrest and that the p53 transcriptional transactivity requires oligomerization of the p53 protein. These and other data indicate that the CTD of p53 is an important component of p53-mediated apoptosis and cell growth arrest and that inactivation of the apoptotic function, but not the inhibition of growth, is an important step during human tumorigenesis. JF - Cancer research AU - Zhou, X AU - Wang, X W AU - Xu, L AU - Hagiwara, K AU - Nagashima, M AU - Wolkowicz, R AU - Zurer, I AU - Rotter, V AU - Harris, C C AD - Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02/15/ PY - 1999 DA - 1999 Feb 15 SP - 843 EP - 848 VL - 59 IS - 4 SN - 0008-5472, 0008-5472 KW - Tumor Suppressor Protein p53 KW - 0 KW - DNA KW - 9007-49-2 KW - Index Medicus KW - Cells, Cultured KW - Humans KW - DNA -- metabolism KW - Mutation KW - Structure-Activity Relationship KW - Cell Division KW - Tumor Suppressor Protein p53 -- physiology KW - Apoptosis KW - Tumor Suppressor Protein p53 -- chemistry KW - Transcriptional Activation UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69589198?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=COOH-terminal+domain+of+p53+modulates+p53-mediated+transcriptional+transactivation%2C+cell+growth%2C+and+apoptosis.&rft.au=Zhou%2C+X%3BWang%2C+X+W%3BXu%2C+L%3BHagiwara%2C+K%3BNagashima%2C+M%3BWolkowicz%2C+R%3BZurer%2C+I%3BRotter%2C+V%3BHarris%2C+C+C&rft.aulast=Zhou&rft.aufirst=X&rft.date=1999-02-15&rft.volume=59&rft.issue=4&rft.spage=843&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-04 N1 - Date created - 1999-03-04 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of conformation-dependent anti-gp120 murine monoclonal antibodies produced by immunization with monomeric and oligomeric human immunodeficiency virus type 1 envelope proteins. AN - 69577106; 9986792 AB - Twenty-five conformation-dependent monoclonal antibodies (MAbs) produced by immunization of mice with oligomeric forms of the human immunodeficiency virus type 1 (HIV-1) envelope (env) glycoprotein were used to map exposed, immunogenic regions on oligomeric env. Based on MAb cross-competition, reactivity with diverse env proteins, and reactivity with a panel of gp120 mutants, seven distinct epitope clusters were identified. These include the classic CD4 binding site, V1/V2, and V3. in addition, several novel epitope clusters, including one mapping to the N- and C-termini of gp120, were identified. The locations of the seven epitope clusters on the gp120 core structure are proposed. JF - Virology AU - Sugiura, W AU - Broder, C C AU - Moss, B AU - Earl, P L AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0445, USA. Y1 - 1999/02/15/ PY - 1999 DA - 1999 Feb 15 SP - 257 EP - 267 VL - 254 IS - 2 SN - 0042-6822, 0042-6822 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD4 KW - Gene Products, env KW - HIV Envelope Protein gp120 KW - Index Medicus KW - AIDS/HIV KW - Animals KW - Models, Molecular KW - Humans KW - Mice KW - Antigens, CD4 -- immunology KW - Cross Reactions KW - Antigens, CD4 -- metabolism KW - Biosensing Techniques KW - Mutagenesis, Site-Directed KW - Gene Products, env -- metabolism KW - Binding, Competitive KW - Neutralization Tests KW - Gene Products, env -- immunology KW - Enzyme-Linked Immunosorbent Assay KW - Epitope Mapping KW - Cell Line KW - Protein Conformation KW - HIV-1 -- immunology KW - HIV Envelope Protein gp120 -- immunology KW - HIV Envelope Protein gp120 -- genetics KW - Antibodies, Monoclonal -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69577106?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Characterization+of+conformation-dependent+anti-gp120+murine+monoclonal+antibodies+produced+by+immunization+with+monomeric+and+oligomeric+human+immunodeficiency+virus+type+1+envelope+proteins.&rft.au=Sugiura%2C+W%3BBroder%2C+C+C%3BMoss%2C+B%3BEarl%2C+P+L&rft.aulast=Sugiura&rft.aufirst=W&rft.date=1999-02-15&rft.volume=254&rft.issue=2&rft.spage=257&rft.isbn=&rft.btitle=&rft.title=Virology&rft.issn=00426822&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-09 N1 - Date created - 1999-03-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells. AN - 69563991; 9933022 AB - Excision repair cross complementation group 1 (ERCC-1) is a DNA repair gene that is essential for life, and it appears to be a marker gene for nucleotide excision repair activity. Overexpression of ERCC-1 during cisplatin-based chemotherapy is associated with clinical and cellular drug resistance. We therefore began to assess the influence of various pharmacological agents on the induction of ERCC-1 mRNA in A2780/CP70 human ovarian carcinoma cells. Cisplatin exposure in culture resulted in a 4- to 6-fold induction for the steady-state level of ERCC-1 mRNA in A2780/CP70 cells. ERCC-1 mRNA induction was concentration and time dependent. Cyclosporin A and herbimycin A, which suppress c-fos and c-jun gene expressions, respectively, blocked the cisplatin-induced increase in ERCC-1 mRNA. This effect of cyclosporin A or herbimycin A on the down-regulation of ERCC-1 correlates with enhanced cytotoxicity of cisplatin in this system. The products of c-fos and c-jun are components of the transcription factor AP-1 (activator protein 1). 12-O-Tetradecanoylphorbol 13-acetate (TPA), a known AP-1 agonist, induced ERCC-1 mRNA to the same extent as cisplatin, but did not synergize with cisplatin in this regard. The TPA effect was biphasic, with an initial increase during the first 1-6 hr, followed by decreasing mRNA levels at 24-72 hr. These data suggest that the effects of these pharmacological agents on ERCC-1 gene expression may be mediated through the modulation of AP-1 activities. JF - Biochemical pharmacology AU - Li, Q AU - Tsang, B AU - Bostick-Bruton, F AU - Reed, E AD - Medical Ovarian Cancer Section, Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02/15/ PY - 1999 DA - 1999 Feb 15 SP - 347 EP - 353 VL - 57 IS - 4 SN - 0006-2952, 0006-2952 KW - Benzoquinones KW - 0 KW - DNA-Binding Proteins KW - Lactams, Macrocyclic KW - Proteins KW - Quinones KW - RNA, Messenger KW - Rifabutin KW - 1W306TDA6S KW - herbimycin KW - 70563-58-5 KW - Cyclosporine KW - 83HN0GTJ6D KW - ERCC1 protein, human KW - EC 3.1.- KW - Endonucleases KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Cisplatin KW - Q20Q21Q62J KW - Index Medicus KW - Protein Biosynthesis KW - Rifabutin -- analogs & derivatives KW - Tumor Cells, Cultured KW - Humans KW - Cyclosporine -- pharmacology KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Quinones -- pharmacology KW - RNA, Messenger -- biosynthesis KW - DNA Repair KW - Cisplatin -- pharmacology KW - Gene Expression Regulation -- drug effects KW - Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563991?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+pharmacology&rft.atitle=Modulation+of+excision+repair+cross+complementation+group+1+%28ERCC-1%29+mRNA+expression+by+pharmacological+agents+in+human+ovarian+carcinoma+cells.&rft.au=Li%2C+Q%3BTsang%2C+B%3BBostick-Bruton%2C+F%3BReed%2C+E&rft.aulast=Li&rft.aufirst=Q&rft.date=1999-02-15&rft.volume=57&rft.issue=4&rft.spage=347&rft.isbn=&rft.btitle=&rft.title=Biochemical+pharmacology&rft.issn=00062952&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-10 N1 - Date created - 1999-02-10 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Kir6.2 oligoantisense administered into the globus pallidus reduces apomorphine-induced turning in 6-OHDA hemiparkinsonian rats. AN - 69634907; 10082813 AB - ATP-sensitive inwardly rectifying potassium channels (KATPs) couple cell metabolism with its membrane potential. The best characterized KATP is the pancreatic KATP which is an heteromultimer of Kir6.2 and SUR1 protein subunits. KATPs are found in a variety of excitable cells, including neurons of the central nervous system. Basal ganglia (BG), especially in the substantia nigra (SN) reticulata and the globus pallidus (GP), have a high density of KATPs. Pharmacological modulation of the KATPs within the BG alters GABAergic activity and produces behavioural changes. However, the relatively high concentrations of drugs used might not have been entirely selective for the KATPs and may have acted at presynaptic nerve terminals as well as on the post-synaptic neurons. As an alternative means of examining the role of KATPs in regulating motor behavior, we used oligoantisense technology to diminish selectively Kir6.2 formation in the GP neurons. We then examined the effect of reduction in Kir6.2 expression on apomorphine-induced turning behavior in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the SN. Two weeks after injection of 6-OHDA, contralateral circling in response to apomorphine (0.25 mg/kg sc) was recorded. Kir6.2 antisense oligodeoxyribonucleotide (ODN) was then administered daily for 6 days into the GP ipsilateral to the 6-OHDA injection. Responses to apomorphine were then tested again and the animals killed to determine the effect of the antisense ODN on Kir6. 2 mRNA. Administration of Kir6.2 antisense ODN significantly attenuated apomorphine-induced contralateral turning and specifically reduced Kir6.2 mRNA in the injected GP. These results are consistent with pharmacological experiments which suggest that KATP channels in the GP are involved in motor responses to apomorphine in 6-OHDA lesioned rats, localizing the effects to the GP neurons, probably through modulation of the GABAergic system. Copyright 1999 Elsevier Science B.V. JF - Brain research AU - Lamensdorf, I AU - Meiri, N AU - Harvey-White, J AU - Jacobowitz, D M AU - Kopin, I J AD - National Institute of Neurological Disorders and Stroke, Clinical Neuroscience Branch, National Institute of Health, Bethesda, MD 20892, USA. il25v@nih.gov Y1 - 1999/02/13/ PY - 1999 DA - 1999 Feb 13 SP - 275 EP - 284 VL - 818 IS - 2 SN - 0006-8993, 0006-8993 KW - Oligodeoxyribonucleotides, Antisense KW - 0 KW - Peptide Fragments KW - Oxidopamine KW - 8HW4YBZ748 KW - Apomorphine KW - N21FAR7B4S KW - Index Medicus KW - Rats KW - Animals KW - Rats, Sprague-Dawley KW - Neurons -- drug effects KW - Motor Activity -- drug effects KW - Rotation KW - Male KW - Parkinson Disease, Secondary -- pathology KW - Apomorphine -- antagonists & inhibitors KW - Oxidopamine -- toxicity KW - Peptide Fragments -- pharmacology KW - Globus Pallidus -- drug effects KW - Oligodeoxyribonucleotides, Antisense -- pharmacology KW - Parkinson Disease, Secondary -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69634907?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Kir6.2+oligoantisense+administered+into+the+globus+pallidus+reduces+apomorphine-induced+turning+in+6-OHDA+hemiparkinsonian+rats.&rft.au=Lamensdorf%2C+I%3BMeiri%2C+N%3BHarvey-White%2C+J%3BJacobowitz%2C+D+M%3BKopin%2C+I+J&rft.aulast=Lamensdorf&rft.aufirst=I&rft.date=1999-02-13&rft.volume=818&rft.issue=2&rft.spage=275&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Intermolecular cleavage by UmuD-like enzymes: identification of residues required for cleavage and substrate specificity. AN - 69573979; 9925794 AB - The UmuD-like proteins are best characterized for their role in damage-induced SOS mutagenesis. An essential step in this process is the enzymatic self-processing of the UmuD-like proteins. This reaction is thought to occur either via an intramolecular or intermolecular self-cleavage mechanism. Here, we demonstrate that it can also occur via an heterologous intermolecular cleavage reaction. The Escherichia coli UmuD enzyme demonstrated the broadest substrate specificity, cleaving both E. coli and Salmonella typhimurium UmuD substrates in vivo. In comparison, the wild-type S. typhimurium UmuD (UmuDSt) and MucA enzymes catalyzed intermolecular self-cleavage, but did not facilitate heterologous cleavage. Heterologous cleavage by the UmuDSt enzyme was, however, observed with chimeric UmuD substrates that possess residues 30-55 of UmuDSt. We have further localized the residue predominantly responsible for UmuDSt-catalyzed heterologous cleavage to Ser50 in the substrate molecule. We hypothesize that changes at this residue affect the positioning of the cleavage site of a substrate molecule within the catalytic cleft of the UmuDSt enzyme by affecting the formation of a so-called UmuD "filament-dimer". This hypothesis is further supported by the observation that mutations known to disrupt an E. coli UmuD' filament dimer also block intermolecular UmuDEc cleavage. Copyright 1998 Academic Press. JF - Journal of molecular biology AU - McDonald, J P AU - Peat, T S AU - Levine, A S AU - Woodgate, R AD - Section on DNA Replication Repair and Mutagenesis National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892-2725, USA. Y1 - 1999/02/05/ PY - 1999 DA - 1999 Feb 05 SP - 2199 EP - 2209 VL - 285 IS - 5 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - Escherichia coli Proteins KW - MucA protein, Bacteria KW - Recombinant Proteins KW - DNA-Directed DNA Polymerase KW - EC 2.7.7.7 KW - UmuD protein, E coli KW - Index Medicus KW - Salmonella typhimurium -- chemistry KW - Plasmids -- genetics KW - Dimerization KW - Amino Acid Sequence KW - Recombinant Proteins -- genetics KW - Salmonella typhimurium -- enzymology KW - Mutagenesis, Site-Directed KW - Recombinant Proteins -- metabolism KW - Molecular Sequence Data KW - Substrate Specificity KW - Recombinant Proteins -- chemistry KW - Salmonella typhimurium -- genetics KW - Mutation KW - Catalysis KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Bacterial Proteins -- metabolism KW - Escherichia coli -- genetics KW - Escherichia coli -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69573979?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Intermolecular+cleavage+by+UmuD-like+enzymes%3A+identification+of+residues+required+for+cleavage+and+substrate+specificity.&rft.au=McDonald%2C+J+P%3BPeat%2C+T+S%3BLevine%2C+A+S%3BWoodgate%2C+R&rft.aulast=McDonald&rft.aufirst=J&rft.date=1999-02-05&rft.volume=285&rft.issue=5&rft.spage=2199&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Enzyme activity of macrophage migration inhibitory factor toward oxidized catecholamines. AN - 69565859; 9920865 AB - Macrophage migration inhibitory factor (MIF) is a relatively small, 12.5-kDa protein that is structurally related to some isomerases and for which multiple immune and catalytic roles have been proposed. MIF is widely expressed in tissues with particularly high levels in neural tissues. Here we show that MIF is able to catalyze the conversion of 3,4-dihydroxyphenylaminechrome and norepinephrinechrome, toxic quinone products of the neurotransmitter catecholamines 3,4-dihydroxyphenylamine and norepinephrine, to indoledihydroxy derivatives that may serve as precursors to neuromelanin. This raises the possibility that MIF participates in a detoxification pathway for catecholamine products and could therefore have a protective role in neural tissues, which as in Parkinson's disease, may be subject to catecholamine-related cell death. JF - The Journal of biological chemistry AU - Matsunaga, J AU - Sinha, D AU - Pannell, L AU - Santis, C AU - Solano, F AU - Wistow, G J AU - Hearing, V J AD - Pigment Cell Biology Section, Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/02/05/ PY - 1999 DA - 1999 Feb 05 SP - 3268 EP - 3271 VL - 274 IS - 6 SN - 0021-9258, 0021-9258 KW - Catecholamines KW - 0 KW - DNA Primers KW - Macrophage Migration-Inhibitory Factors KW - Recombinant Proteins KW - Index Medicus KW - Oxidation-Reduction KW - Animals KW - Aging -- metabolism KW - Base Sequence KW - Recombinant Proteins -- metabolism KW - Humans KW - Mice KW - Brain -- metabolism KW - Macrophage Migration-Inhibitory Factors -- metabolism KW - Catecholamines -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69565859?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Enzyme+activity+of+macrophage+migration+inhibitory+factor+toward+oxidized+catecholamines.&rft.au=Matsunaga%2C+J%3BSinha%2C+D%3BPannell%2C+L%3BSantis%2C+C%3BSolano%2C+F%3BWistow%2C+G+J%3BHearing%2C+V+J&rft.aulast=Matsunaga&rft.aufirst=J&rft.date=1999-02-05&rft.volume=274&rft.issue=6&rft.spage=3268&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-26 N1 - Date created - 1999-02-26 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Mycolactone: A polyketide toxin from Mycobacterium ulcerans required for virulence AN - 17162343; 4457037 AB - Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe human skin disease that occurs primarily in Africa and Australia. Infection with M. ulcerans results in persistent severe necrosis without an acute inflammatory response. The presence of histopathological changes distant from the site of infection suggested that pathogenesis might be toxin mediated. A polyketide-derived macrolide designated mycolactone was isolated that causes cytopathicity and cell cycle arrest in cultured L929 murine fibroblasts. Intradermal inoculation of purified toxin into guinea pigs produced a lesion similar to that of Buruli ulcer in humans. This toxin may represent one of a family of virulence factors associated with pathology in mycobacterial diseases such as leprosy and tuberculosis. JF - Science (Washington) AU - George, K M AU - Chatterjee, D AU - Gunawardana, G AU - Welty, D AU - Hayman, J AU - Lee, R AU - Small, PLC AD - Rocky Mountain Lab., Natl. Inst. Allergy and Infect. Dis., NIH, Hamilton, MT 59840, USA, psmall@nih.gov Y1 - 1999/02/05/ PY - 1999 DA - 1999 Feb 05 SP - 854 EP - 857 PB - American Association for the Advancement of Science VL - 283 IS - 5403 SN - 0036-8075, 0036-8075 KW - Buruli ulcer KW - guinea-pigs KW - mycolactone KW - polyketides KW - Microbiology Abstracts B: Bacteriology; Toxicology Abstracts KW - Virulence KW - Mycobacterium ulcerans KW - Skin diseases KW - Toxins KW - X 24171:Microbial KW - J 02823:In vitro and in vivo effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17162343?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Mycolactone%3A+A+polyketide+toxin+from+Mycobacterium+ulcerans+required+for+virulence&rft.au=George%2C+K+M%3BChatterjee%2C+D%3BGunawardana%2C+G%3BWelty%2C+D%3BHayman%2C+J%3BLee%2C+R%3BSmall%2C+PLC&rft.aulast=George&rft.aufirst=K&rft.date=1999-02-05&rft.volume=283&rft.issue=5403&rft.spage=854&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Mycobacterium ulcerans; Virulence; Toxins; Skin diseases ER - TY - JOUR T1 - Mismatch Extension by Escherichia coli DNA Polymerase III Holoenzyme AN - 17160497; 4456093 AB - The in vitro fidelity of Escherichia coli DNA polymerase III holoenzyme (HE) is characterized by an unusual propensity for generating (-1)-frameshift mutations. Here we have examined the capability of HE isolated from both a wild-type and a proofreading-impaired mutD5 strain to polymerize from M13mp2 DNA primer-templates containing a terminal T(template) super(.)C mismatch. These substrates contained either an A or a G as the next (5') template base. The assay allows distinction between: (i) direct extension of the terminal C (producing a base substitution), (ii) exonucleolytic removal of the C, or (iii) for the G-containing template, extension after misalignment of the C on the next template G (producing a (-1)-frameshift). On the A-containing substrate, both HEs did not extend the terminal C (99%). In contrast, on the G-containing substrate, the MutD5 HE yielded 61% (-1)-frameshifts and 6% base substitutions. The wild-type HE mostly excised the mispaired C from this substrate before extension (98%), but among the 2% mutants (-1)-frameshifts exceeded base substitutions by 20 to 1. The preference of polymerase III HE for misalignment extension over direct mismatch extension provides a basis for explaining the in vitro (-1)-frameshift specificity of polymerase III HE. JF - Journal of Biological Chemistry AU - Pham, P T AU - Olson, M W AU - McHenry, C S AU - Schaaper, R M AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709 Y1 - 1999/02/05/ PY - 1999 DA - 1999 Feb 05 SP - 3705 EP - 3710 VL - 274 IS - 6 SN - 0021-9258, 0021-9258 KW - Microbiology Abstracts B: Bacteriology; Biochemistry Abstracts 2: Nucleic Acids KW - DNA-directed DNA polymerase KW - Escherichia coli KW - J 02725:DNA KW - N 14722:DNA polymerases UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17160497?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Mismatch+Extension+by+Escherichia+coli+DNA+Polymerase+III+Holoenzyme&rft.au=Pham%2C+P+T%3BOlson%2C+M+W%3BMcHenry%2C+C+S%3BSchaaper%2C+R+M&rft.aulast=Pham&rft.aufirst=P&rft.date=1999-02-05&rft.volume=274&rft.issue=6&rft.spage=3705&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Escherichia coli; DNA-directed DNA polymerase ER - TY - JOUR T1 - [Recurrent hyponatremia, neurological symptoms and long-term administration of levomepromazine]. TT - Rezidivierende Hyponatriämien, neurologische Symptomatik und jahrelange Einnahme von Levomepromazin. AN - 69633964; 10081342 AB - We present the case of an 84 year old lady with an episode of marked hyponatremia with acute neurological disturbances which in the latest case resolved completely after a 3 day period of fluid restriction. The more common causes of hyponatremia could be ruled out. There was no evidence for a neuroleptic drug associated change in serum sodium concentration. We conclude that the patient in this study belongs to a subset of geriatric patients in whom there is an intermittent SIADH which only becomes clinically evident when several factors coincide. The underlying mechanisms are not understood but could include the interaction of subclinical cerebrovascular disease and treatment with a neuroleptic drug in an elderly patient whose water and sodium homeostasis is compromised by the changes of normal aging which affect the many systems involved in maintaining water and sodium balance. JF - Praxis AU - Münzer, T AU - Gründler, B M AU - Miller, M AD - Gerontology Research Center, National Institute on Aging, Baltimore, USA. Y1 - 1999/02/04/ PY - 1999 DA - 1999 Feb 04 SP - 237 EP - 241 VL - 88 IS - 6 SN - 1661-8157, 1661-8157 KW - Index Medicus KW - Animals KW - Guinea Pigs KW - Aged, 80 and over KW - Humans KW - Water Intoxication -- chemically induced KW - Dyskinesia, Drug-Induced -- diagnosis KW - Aged KW - Water Intoxication -- diagnosis KW - Inappropriate ADH Syndrome -- chemically induced KW - Recurrence KW - Male KW - Inappropriate ADH Syndrome -- diagnosis KW - Hyponatremia -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69633964?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Praxis&rft.atitle=%5BRecurrent+hyponatremia%2C+neurological+symptoms+and+long-term+administration+of+levomepromazine%5D.&rft.au=M%C3%BCnzer%2C+T%3BGr%C3%BCndler%2C+B+M%3BMiller%2C+M&rft.aulast=M%C3%BCnzer&rft.aufirst=T&rft.date=1999-02-04&rft.volume=88&rft.issue=6&rft.spage=237&rft.isbn=&rft.btitle=&rft.title=Praxis&rft.issn=16618157&rft_id=info:doi/ LA - ger DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-08 N1 - Date created - 1999-06-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of leukemia after platinum-based chemotherapy for ovarian cancer. AN - 69559100; 9929525 AB - Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia. JF - The New England journal of medicine AU - Travis, L B AU - Holowaty, E J AU - Bergfeldt, K AU - Lynch, C F AU - Kohler, B A AU - Wiklund, T AU - Curtis, R E AU - Hall, P AU - Andersson, M AU - Pukkala, E AU - Sturgeon, J AU - Stovall, M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. Y1 - 1999/02/04/ PY - 1999 DA - 1999 Feb 04 SP - 351 EP - 357 VL - 340 IS - 5 SN - 0028-4793, 0028-4793 KW - Antineoplastic Agents KW - 0 KW - Antineoplastic Agents, Alkylating KW - Carboplatin KW - BG3F62OND5 KW - Cisplatin KW - Q20Q21Q62J KW - Melphalan KW - Q41OR9510P KW - Abridged Index Medicus KW - Index Medicus KW - Logistic Models KW - Dose-Response Relationship, Drug KW - Risk Factors KW - Humans KW - Melphalan -- adverse effects KW - Case-Control Studies KW - Combined Modality Therapy -- adverse effects KW - Antineoplastic Agents, Alkylating -- adverse effects KW - Aged KW - Middle Aged KW - Female KW - Leukemia -- radiotherapy KW - Leukemia -- chemically induced KW - Cisplatin -- adverse effects KW - Carboplatin -- adverse effects KW - Ovarian Neoplasms -- drug therapy KW - Antineoplastic Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69559100?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+journal+of+medicine&rft.atitle=Risk+of+leukemia+after+platinum-based+chemotherapy+for+ovarian+cancer.&rft.au=Travis%2C+L+B%3BHolowaty%2C+E+J%3BBergfeldt%2C+K%3BLynch%2C+C+F%3BKohler%2C+B+A%3BWiklund%2C+T%3BCurtis%2C+R+E%3BHall%2C+P%3BAndersson%2C+M%3BPukkala%2C+E%3BSturgeon%2C+J%3BStovall%2C+M&rft.aulast=Travis&rft.aufirst=L&rft.date=1999-02-04&rft.volume=340&rft.issue=5&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=The+New+England+journal+of+medicine&rft.issn=00284793&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-09 N1 - Date created - 1999-02-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The Relationship between Context and the Organisation of Repair in the L2 Classroom AN - 85694988; 9908739 AB - It is proposed that different contexts occur in second-language classrooms & that repair is organized differently within each context. It is suggested that within each context a particular pedagogical focus combines with a particular organization of repair which is appropriate to that focus. The organization of repair within each context is sketched & exemplified through analysis of classroom transcripts. 36 References. Adapted from the source document JF - IRAL AU - Seedhouse, Paul AD - Centre for International Studies in Education St. Thomas St U of Newcastle, Newcastle NEI 7RU UK paul.seedhouse@ncl.ac.uk Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 59 EP - 80 VL - 37 IS - 1 SN - 0019-042X, 0019-042X KW - Repair (72920) KW - Classroom Communication (12250) KW - Second Language Instruction (75700) KW - Context (15250) KW - article KW - 4112: applied linguistics; non-native language pedagogy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85694988?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Allba&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=IRAL&rft.atitle=The+Relationship+between+Context+and+the+Organisation+of+Repair+in+the+L2+Classroom&rft.au=Seedhouse%2C+Paul&rft.aulast=Seedhouse&rft.aufirst=Paul&rft.date=1999-02-01&rft.volume=37&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=IRAL&rft.issn=0019042X&rft_id=info:doi/ LA - English DB - Linguistics and Language Behavior Abstracts (LLBA) N1 - Date revised - 2003-10-01 N1 - Last updated - 2016-09-27 N1 - CODEN - IRALA4 N1 - SubjectsTermNotLitGenreText - Classroom Communication (12250); Second Language Instruction (75700); Repair (72920); Context (15250) ER - TY - JOUR T1 - Risk of leukemia after platinum-based chemotherapy for ovarian cancer. AN - 85231054; pmid-9929525 AB - BACKGROUND: Platinum-based chemotherapy is the cornerstone of modern treatment for ovarian, testicular, and other cancers, but few investigations have quantified the late sequelae of such treatment. METHODS: We conducted a case-control study of secondary leukemia in a population-based cohort of 28,971 women in North America and Europe who had received a diagnosis of invasive ovarian cancer between 1980 and 1993. Leukemia developed after the administration of platinum-based therapy in 96 women. These women were matched to 272 control patients. The type, cumulative dose, and duration of chemotherapy and the dose of radiation delivered to active bone marrow were compared in the two groups. RESULTS: Among the women who received platinum-based combination chemotherapy for ovarian cancer, the relative risk of leukemia was 4.0 (95 percent confidence interval, 1.4 to 11.4). The relative risks for treatment with carboplatin and for treatment with cisplatin were 6.5 (95 percent confidence interval, 1.2 to 36.6) and 3.3 (95 percent confidence interval, 1.1 to 9.4), respectively. We found evidence of a dose-response relation, with relative risks reaching 7.6 at doses of 1000 mg or more of platinum (P for trend <0.001). Radiotherapy without chemotherapy (median dose, 18.4 Gy) did not increase the risk of leukemia. CONCLUSIONS: Platinum-based treatment of ovarian cancer increases the risk of secondary leukemia. Nevertheless, the substantial benefit that platinum-based treatment offers patients with advanced disease outweighs the relatively small excess risk of leukemia. JF - The New England Journal of Medicine AU - Travis, L B AU - Holowaty, E J AU - Bergfeldt, K AU - Lynch, C F AU - Kohler, B A AU - Wiklund, T AU - Curtis, R E AU - Hall, P AU - Andersson, M AU - Pukkala, E AU - Sturgeon, J AU - Stovall, M AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. PY - 1999 SP - 351 EP - 357 VL - 340 IS - 5 SN - 0028-4793, 0028-4793 KW - Melphalan KW - Ovarian Neoplasms KW - Antineoplastic Agents KW - Combined Modality Therapy KW - Dose-Response Relationship, Drug KW - Human KW - Aged KW - Carboplatin KW - Leukemia KW - Cisplatin KW - Logistic Models KW - Risk Factors KW - Case-Control Studies KW - Middle Age KW - Antineoplastic Agents, Alkylating KW - Female UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/85231054?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Acomdisdome&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+New+England+Journal+of+Medicine&rft.atitle=Risk+of+leukemia+after+platinum-based+chemotherapy+for+ovarian+cancer.&rft.au=Travis%2C+L+B%3BHolowaty%2C+E+J%3BBergfeldt%2C+K%3BLynch%2C+C+F%3BKohler%2C+B+A%3BWiklund%2C+T%3BCurtis%2C+R+E%3BHall%2C+P%3BAndersson%2C+M%3BPukkala%2C+E%3BSturgeon%2C+J%3BStovall%2C+M&rft.aulast=Travis&rft.aufirst=L&rft.date=1999-02-01&rft.volume=340&rft.issue=5&rft.spage=351&rft.isbn=&rft.btitle=&rft.title=The+New+England+Journal+of+Medicine&rft.issn=00284793&rft_id=info:doi/ LA - eng DB - ComDisDome N1 - Last updated - 2010-05-07 ER - TY - JOUR T1 - Drinking water disinfection byproducts: review and approach to toxicity evaluation. AN - 69922691; 10229719 AB - There is widespread potential for human exposure to disinfection byproducts (DBPs) in drinking water because everyone drinks, bathes, cooks, and cleans with water. The need for clean and safe water led the U.S. Congress to pass the Safe Drinking Water Act more than 20 years ago in 1974. In 1976, chloroform, a trihalomethane (THM) and a principal DBP, was shown to be carcinogenic in rodents. This prompted the U.S. Environmental Protection Agency (U.S. EPA) in 1979 to develop a drinking water rule that would provide guidance on the levels of THMs allowed in drinking water. Further concern was raised by epidemiology studies suggesting a weak association between the consumption of chlorinated drinking water and the occurrence of bladder, colon, and rectal cancer. In 1992 the U.S. EPA initiated a negotiated rulemaking to evaluate the need for additional controls for microbial pathogens and DBPs. The goal was to develop an approach that would reduce the level of exposure from disinfectants and DBPs without undermining the control of microbial pathogens. The product of these deliberations was a proposed stage 1 DBP rule. It was agreed that additional information was necessary on how to optimize the use of disinfectants while maintaining control of pathogens before further controls to reduce exposure beyond stage 1 were warranted. In response to this need, the U.S. EPA developed a 5-year research plan to support the development of the longer term rules to control microbial pathogens and DBPs. A considerable body of toxicologic data has been developed on DBPs that occur in the drinking water, but the main emphasis has been on THMs. Given the complexity of the problem and the need for additional data to support the drinking water DBP rules, the U.S. EPA, the National Institute of Environmental Health Sciences, and the U.S. Army are working together to develop a comprehensive biologic and mechanistic DBP database. Selected DBPs will be tested using 2-year toxicity and carcinogenicity studies in standard rodent models; transgenic mouse models and small fish models; in vitro mechanistic and toxicokinetic studies; and reproductive, immunotoxicity, and developmental studies. The goal is to create a toxicity database that reflects a wide range of DBPs resulting from different disinfection practices. This paper describes the approach developed by these agencies to provide the information needed to make scientifically based regulatory decisions. JF - Environmental health perspectives AU - Boorman, G A AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. boorman@niehs.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 207 EP - 217 VL - 107 Suppl 1 SN - 0091-6765, 0091-6765 KW - Acetates KW - 0 KW - Hydrocarbons, Brominated KW - Trihalomethanes KW - Trichloroacetic Acid KW - 5V2JDO056X KW - dibromoacetic acid KW - 631-64-1 KW - Ozone KW - 66H7ZZK23N KW - Chloroform KW - 7V31YC746X KW - Dichloroacetic Acid KW - 9LSH52S3LQ KW - bromoform KW - TUT9J99IMU KW - Index Medicus KW - Animals KW - Dichloroacetic Acid -- toxicity KW - Trichloroacetic Acid -- toxicity KW - DNA Damage KW - Humans KW - Fishes KW - Chloroform -- toxicity KW - Mice KW - Acetates -- toxicity KW - Hydrocarbons, Brominated -- toxicity KW - Ozone -- toxicity KW - Disinfection KW - Water Supply -- standards UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69922691?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+health+perspectives&rft.atitle=Drinking+water+disinfection+byproducts%3A+review+and+approach+to+toxicity+evaluation.&rft.au=Boorman%2C+G+A&rft.aulast=Boorman&rft.aufirst=G&rft.date=1999-02-01&rft.volume=107+Suppl+1&rft.issue=&rft.spage=207&rft.isbn=&rft.btitle=&rft.title=Environmental+health+perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2000-07-27 N1 - Date created - 2000-07-27 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Appl Toxicol. 1985 Aug;5(4):261-4 [4045099] Environ Health Perspect. 1995 Nov;103 Suppl 8:225-31 [8741788] Fundam Appl Toxicol. 1985 Dec;5(6 Pt 1):1128-36 [3005099] Environ Mutagen. 1986;8 Suppl 7:1-119 [3516675] Fundam Appl Toxicol. 1986 Apr;6(3):447-53 [3699330] Cancer Res. 1987 Oct 1;47(19):5189-93 [3621204] Toxicol Appl Pharmacol. 1987 Sep 15;90(2):183-9 [3629594] Carcinogenesis. 1987 Oct;8(10):1491-9 [2888545] Fundam Appl Toxicol. 1995 Dec;28(2):155-66 [8835225] Environ Health Perspect. 1996 Oct;104(10):1056-61 [8930546] Cancer Causes Control. 1996 Nov;7(6):596-604 [8932920] Fundam Appl Toxicol. 1996 May;31(1):77-82 [8998956] Toxicology. 1996 Dec 18;114(3):207-21 [8980710] Cancer Res. 1997 Feb 1;57(3):355-61 [9012454] Carcinogenesis. 1997 Apr;18(4):777-81 [9111214] Toxicol Pathol. 1997 Mar-Apr;25(2):202-10 [9125779] Cancer Causes Control. 1997 Mar;8(2):192-200 [9134243] J Natl Cancer Inst. 1997 Jun 18;89(12):848-56 [9196250] Am J Public Health. 1997 Jul;87(7):1168-76 [9240108] J Toxicol Environ Health. 1997 Dec 12;52(5):425-45 [9388534] Epidemiology. 1998 Jan;9(1):21-8 [9430264] J Natl Cancer Inst. 1975 Oct;55(4):909-16 [171429] Cancer Res. 1981 Dec;41(12 Pt 1):4997-5003 [7307000] J Natl Cancer Inst. 1983 Nov;71(5):965-72 [6580498] Fundam Appl Toxicol. 1985 Aug;5(4):760-9 [4043598] J Appl Toxicol. 1985 Aug;5(4):255-60 [4045098] Epidemiology. 1998 Jan;9(1):29-35 [9430265] Toxicol Pathol. 1997 Nov-Dec;25(6):541-8 [9437797] Toxicol Appl Pharmacol. 1998 Jan;148(1):137-47 [9465273] Toxicol Pathol. 1998 Jan-Feb;26(1):104-12 [9502392] Epidemiology. 1998 Mar;9(2):134-40 [9504280] Epidemiology. 1998 Sep;9(5):484-9 [9730025] Toxicol Pathol. 1998 Sep-Oct;26(5):587-94 [9789944] Epidemiology. 1992 Sep;3(5):407-13 [1391132] Carcinogenesis. 1987 Dec;8(12):1959-61 [3677321] Food Chem Toxicol. 1989 Feb;27(2):77-87 [2714719] Toxicology. 1989 May 31;56(1):79-86 [2728008] Cancer Res. 1990 Sep 1;50(17):5504-14 [2386955] Toxicology. 1990 Sep;63(3):341-59 [2219130] Jpn J Cancer Res. 1991 Feb;82(2):165-9 [1900820] Fundam Appl Toxicol. 1991 Feb;16(2):337-47 [2055364] Toxicol Ind Health. 1991 Sep-Nov;7(5-6):423-32 [1780885] Am J Public Health. 1992 Jul;82(7):955-63 [1535181] Fundam Appl Toxicol. 1992 Aug;19(2):159-68 [1516771] Fundam Appl Toxicol. 1992 Aug;19(2):186-96 [1516774] J Environ Pathol Toxicol Oncol. 1992 Sep-Oct;11(5-6):287-92 [1464809] J Natl Cancer Inst. 1993 May 19;85(10):817-22 [8487327] Environ Health Perspect. 1993 Apr;100:249-57 [8354173] Am J Epidemiol. 1993 Oct 1;138(7):492-501 [8213753] Fundam Appl Toxicol. 1994 Jan;22(1):90-102 [8125218] Mutat Res. 1995 Feb;341(4):289-302 [7531288] Carcinogenesis. 1995 Feb;16(2):335-42 [7859366] Carcinogenesis. 1995 Mar;16(3):495-500 [7697804] Carcinogenesis. 1995 Mar;16(3):593-7 [7697818] Science. 1995 Apr 21;268(5209):356-7 [7716533] Toxicology. 1995 Mar 31;97(1-3):59-69 [7716793] Am J Epidemiol. 1995 May 1;141(9):850-62 [7717362] Cancer Lett. 1995 May 25;92(1):67-76 [7538896] Cancer Res. 1995 Sep 1;55(17):3702-5 [7641179] Environ Health Perspect. 1995 Jun;103(6):592-6 [7556013] Eur J Cancer. 1995 Jul-Aug;31A(7-8):1061-4 [7576992] Environ Health Perspect. 1995 Oct;103(10):942-50 [8529591] Ecotoxicol Environ Saf. 1995 Nov;32(2):103-30 [8575356] Fundam Appl Toxicol. 1985 Dec;5(6 Pt 1):1065-74 [4092869] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantity of partial agonist activity for antiglucocorticoids complexed with mutant glucocorticoid receptors is constant in two different transactivation assays but not predictable from steroid structure. AN - 69824527; 10369406 AB - An unsolved question in steroid hormone action is why the amount of agonist activity displayed by antisteroids is not constant but varies with the assay conditions. Receptor mutations have provided insight into hormone action, presumably due to changes in the tertiary structure of the receptor that alter its interaction surfaces with the transcriptional machinery or/and co-factors. We have now employed two mechanistically different induction assays to determine whether disparate transactivation processes are similarly altered by receptor mutations. The two activation assays studied were (i) the standard induction of GREtkLUC in transiently transfected CV-1 cells and (ii) a novel modulation of endogenous receptor activity by transiently transfected receptors in HeLa cells. Five different mutations in the ligand binding and DNA binding domains of the rat glucocorticoid receptor (CS1, CS1/CD, 451/9, C656G, and R732Q) and seven steroids of varied structures (five antagonists and two agonists) were selected for use. The results in both induction assays were the same. However, no generalizations regarding steroid structure and activity emerged. Neither of two potent glucocorticoids were active with GR-CS1, or GR-CS1/CD, while RU 486 was the only antisteroid with appreciable agonist activity. With the GR-451/9 mutant, three antagonists afforded partial agonist activity. We confirmed that the C656G mutant is both "super-sensitive" and "super-selective" for transactivation. In contrast, the R732Q mutation caused significant decreases in activity with both antagonists and subsaturating concentrations of agonists. This inability to generalize about the behavior of any class of steroids with mutant receptors may reflect an induced fit for each receptor steroid complex. Nevertheless, the activity of a given steroid appeared to be constant in two different transactivation assays for a given mutant receptor. Thus, disparate transactivation processes may utilize identical receptor surfaces, even in the expression of partial agonist activity for specific antiglucocorticoids. JF - The Journal of steroid biochemistry and molecular biology AU - Sarlis, N J AU - Bayly, S F AU - Szapary, D AU - Simons, S S AD - Steroid Hormones Section, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 89 EP - 102 VL - 68 IS - 3-4 SN - 0960-0760, 0960-0760 KW - Glucocorticoids KW - 0 KW - Hormone Antagonists KW - Pregnatrienes KW - Receptors, Glucocorticoid KW - Recombinant Fusion Proteins KW - Recombinant Proteins KW - Mifepristone KW - 320T6RNW1F KW - deacylcortivazol KW - 3JO09QT49F KW - Desoxycorticosterone KW - 40GP35YQ49 KW - Dexamethasone KW - 7S5I7G3JQL KW - Index Medicus KW - Recombinant Fusion Proteins -- biosynthesis KW - Animals KW - HeLa Cells KW - Dexamethasone -- pharmacology KW - Humans KW - Mifepristone -- pharmacology KW - Pregnatrienes -- pharmacology KW - Rats KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Proteins -- metabolism KW - Kinetics KW - Cercopithecus aethiops KW - Desoxycorticosterone -- pharmacology KW - Amino Acid Substitution KW - Cell Line KW - Glucocorticoids -- metabolism KW - Receptors, Glucocorticoid -- chemistry KW - Hormone Antagonists -- pharmacokinetics KW - Transcription, Genetic KW - Receptors, Glucocorticoid -- metabolism KW - Transcriptional Activation KW - Glucocorticoids -- pharmacology KW - Hormone Antagonists -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69824527?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.atitle=Quantity+of+partial+agonist+activity+for+antiglucocorticoids+complexed+with+mutant+glucocorticoid+receptors+is+constant+in+two+different+transactivation+assays+but+not+predictable+from+steroid+structure.&rft.au=Sarlis%2C+N+J%3BBayly%2C+S+F%3BSzapary%2C+D%3BSimons%2C+S+S&rft.aulast=Sarlis&rft.aufirst=N&rft.date=1999-02-01&rft.volume=68&rft.issue=3-4&rft.spage=89&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+steroid+biochemistry+and+molecular+biology&rft.issn=09600760&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-25 N1 - Date created - 1999-06-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Serum organochlorine pesticides and PCBs and breast cancer risk: results from a prospective analysis (USA). AN - 69762516; 10334636 AB - To prospectively evaluate relationships of organochlorine pesticides and polychlorinated biphenyls (PCBs) with breast cancer, we conducted a case-control study nested in a cohort using the Columbia, Missouri Breast Cancer Serum Bank. Women donated blood in 1977-87, and during up to 9.5 years follow-up, 105 donors who met the inclusion criteria for the current study were diagnosed with breast cancer. For each case, two controls matched on age and date of blood collection were selected. Five DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] analogs, 13 other organochlorine pesticides, and 27 PCBs were measured in serum. Women in the upper three quartiles of hexachlorobenzene were at twice the risk of breast cancer compared to those in the lowest quartile. However, there was no evidence for a dose-response relationship, and the association was limited to women whose blood was collected close to the time of diagnosis. Women with higher serum levels of other organochlorine pesticides and PCBs showed no increased risk of breast cancer overall, although positive associations were suggested for PCB-118 and PCB-138 when blood was collected close to the time of diagnosis. Results of this study do not support a role for organochlorine pesticides and PCBs in breast cancer etiology. JF - Cancer causes & control : CCC AU - Dorgan, J F AU - Brock, J W AU - Rothman, N AU - Needham, L L AU - Miller, R AU - Stephenson, H E AU - Schussler, N AU - Taylor, P R AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7374, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 1 EP - 11 VL - 10 IS - 1 SN - 0957-5243, 0957-5243 KW - Insecticides KW - 0 KW - DDT KW - CIW5S16655 KW - Polychlorinated Biphenyls KW - DFC2HB4I0K KW - Index Medicus KW - Prospective Studies KW - Humans KW - DDT -- blood KW - Case-Control Studies KW - Aged KW - Middle Aged KW - DDT -- adverse effects KW - Blood Banks KW - Female KW - Risk Assessment KW - Insecticides -- adverse effects KW - Polychlorinated Biphenyls -- blood KW - Breast Neoplasms -- etiology KW - Breast Neoplasms -- epidemiology KW - Polychlorinated Biphenyls -- adverse effects KW - Insecticides -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69762516?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+causes+%26+control+%3A+CCC&rft.atitle=Serum+organochlorine+pesticides+and+PCBs+and+breast+cancer+risk%3A+results+from+a+prospective+analysis+%28USA%29.&rft.au=Dorgan%2C+J+F%3BBrock%2C+J+W%3BRothman%2C+N%3BNeedham%2C+L+L%3BMiller%2C+R%3BStephenson%2C+H+E%3BSchussler%2C+N%3BTaylor%2C+P+R&rft.aulast=Dorgan&rft.aufirst=J&rft.date=1999-02-01&rft.volume=10&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Cancer+causes+%26+control+%3A+CCC&rft.issn=09575243&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of inhaled alpha-methylstyrene vapor toxicity for B6C3F1 mice and F344 rats. AN - 69721053; 10220856 AB - alpha-Methylstyrene (AMS) is a chemical intermediate used in the synthesis of specialty polymers and copolymers. Inhalation studies of AMS were conducted because of the lack of toxicity data and the structural similarity of AMS to styrene, a toxic and potentially carcinogenic chemical. Male and female B6C3F1 mice were exposed to 0, 600, 800, or 1000 ppm AMS 6 h/day, 5 days/week, for 12 days. After 1 exposure, 21% (5/24) of female mice were found dead in the 1000-ppm group, 56% (10/18) in the 800-ppm group, and 6% (1/18) in the 600-ppm concentration group. After 12 exposures, relative liver weights were significantly increased and relative spleen weights were significantly decreased in both male and female mice at all concentrations. No microscopic treatment-related lesions were observed. A decrease in hepatic glutathione (GSH) was associated with AMS exposure for 1 and 5 days. Male and female F344 rats were exposed to 0, 600 or 1000 ppm AMS for 12 days. No mortality or sedation occurred in AMS-exposed rats. Relative liver weights were significantly increased in both males and females after 12 exposures to 600 or 1000 ppm. An increased hyaline droplet accumulation was detected in male rats in both concentration groups; no significant microscopic lesions were observed in other tissues examined. Exposure of male and female F344 rats and male NBR rats to 0, 125, 250 or 500 ppm AMS, 6 h/day for 9 days resulted in increased accumulation of hyaline droplets in the renal tubules of male F344 rats in the 250 and 500 ppm concentration groups. Although AMS and styrene are structurally very similar, AMS was considerably less toxic for mice and more toxic for male rats than styrene. JF - Toxicological sciences : an official journal of the Society of Toxicology AU - Morgan, D L AU - Mahler, J F AU - Kirkpatrick, D T AU - Price, H C AU - O'Connor, R W AU - Wilson, R E AU - Moorman, M P AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. morgand@niehs.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 187 EP - 194 VL - 47 IS - 2 SN - 1096-6080, 1096-6080 KW - Styrenes KW - 0 KW - vinyltoluene KW - 25013-15-4 KW - Glutathione KW - GAN16C9B8O KW - Index Medicus KW - Animals KW - Spleen -- metabolism KW - Glutathione -- metabolism KW - Volatilization KW - Liver -- metabolism KW - Mice KW - Rats KW - Rats, Inbred F344 KW - Liver -- drug effects KW - Body Weight -- drug effects KW - Toxicity Tests KW - Spleen -- drug effects KW - Administration, Inhalation KW - Female KW - Male KW - Organ Size -- drug effects KW - Styrenes -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69721053?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.atitle=Characterization+of+inhaled+alpha-methylstyrene+vapor+toxicity+for+B6C3F1+mice+and+F344+rats.&rft.au=Morgan%2C+D+L%3BMahler%2C+J+F%3BKirkpatrick%2C+D+T%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BWilson%2C+R+E%3BMoorman%2C+M+P&rft.aulast=Morgan&rft.aufirst=D&rft.date=1999-02-01&rft.volume=47&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Toxicological+sciences+%3A+an+official+journal+of+the+Society+of+Toxicology&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-07 N1 - Date created - 1999-07-07 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exposure of farmers to phosmet, a swine insecticide. AN - 69690403; 10204668 AB - The goal of this study was to measure dermal and inhalation exposures to phosmet during application to animals and to identify what determinants of exposure influence the exposure levels. Ten farmers were monitored using dermal patches, gloves, and air sampling media during normal activities of applying phosmet to pigs for insect control. Exposures were measured on the clothing (outer), under the clothing (inner), on the hands, and in the air. Possible exposure determinants were identified, and a questionnaire on work practices was administered. The geometric mean of the outer exposure measurements was 79 microg/h, whereas the geometric mean of the inner exposure measurements was 6 microg/h. The geometric mean for hand exposure was 534 microg/h, and the mean air concentration was 0.2 microg/m3. Glove use was associated with the hand and total dermal exposure levels, but no other determinant was associated with any of the exposure measures. The average penetration through the clothing was 54%, which dropped to 8% when the farmers wearing short sleeves were excluded. The farmers reported an average of 40 hours a year performing insecticide-related tasks. Farmers who applied phosmet to animals had measurable exposures, but the levels were lower than what has been seen in other pesticide applications. Inhalation exposures were insignificant when compared with dermal exposures, which came primarily from the hands. Clothing, particularly gloves, provided substantial protection from exposures. No other exposure determinant was identified. JF - Scandinavian journal of work, environment & health AU - Stewart, P A AU - Fears, T AU - Kross, B AU - Ogilvie, L AU - Blair, A AD - National Cancer Institute, Bethesda, Maryland 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 33 EP - 38 VL - 25 IS - 1 SN - 0355-3140, 0355-3140 KW - Insecticides KW - 0 KW - Phosmet KW - VN04LI540Y KW - Index Medicus KW - Swine KW - Regression Analysis KW - Gloves, Protective KW - Animals KW - Protective Clothing KW - Skin Absorption KW - Inhalation Exposure KW - Humans KW - Iowa KW - Occupational Exposure -- prevention & control KW - Animal Husbandry KW - Phosmet -- analysis KW - Insecticides -- analysis KW - Occupational Exposure -- analysis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69690403?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Scandinavian+journal+of+work%2C+environment+%26+health&rft.atitle=Exposure+of+farmers+to+phosmet%2C+a+swine+insecticide.&rft.au=Stewart%2C+P+A%3BFears%2C+T%3BKross%2C+B%3BOgilvie%2C+L%3BBlair%2C+A&rft.aulast=Stewart&rft.aufirst=P&rft.date=1999-02-01&rft.volume=25&rft.issue=1&rft.spage=33&rft.isbn=&rft.btitle=&rft.title=Scandinavian+journal+of+work%2C+environment+%26+health&rft.issn=03553140&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-25 N1 - Date created - 1999-05-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characteristics of persons who self-reported a high pesticide exposure event in the Agricultural Health Study. AN - 69651529; 10092411 AB - Characteristics of persons who report high pesticide exposure events (HPEE) were studied in a large cohort of licensed pesticide applicators from Iowa and North Carolina who enrolled in the Agricultural Health Study between December 1993 and December 1995. Fourteen percent reported having "an incident or experience while using any pesticide which caused an unusually high personal exposure. " After taking into account total number of applications made and education, females (OR=0.76), applicators from NC (OR=0.65), and privately licensed applicators (OR=0.65) were less likely to have reported an HPEE. Work practices more common among both private and commercial applicators with an HPEE included delay in changing clothing or washing after pesticide application, mixing pesticide application clothing with the family wash, washing up inside the house after application, applying pesticides within 50 yards of their well, and storing pesticides in the home. Job characteristics more common among those with an HPEE included self-repair of application equipment and first pesticide use more than 10 years in the past. These job characteristics explained much of the difference in reported HPEE between males and females, but not between IA and NC subjects or between commercial or private applicators. Copyright 1999 Academic Press. JF - Environmental research AU - Alavanja, M C AU - Sandler, D P AU - McDonnell, C J AU - Mage, D T AU - Kross, B C AU - Rowland, A S AU - Blair, A AD - Epidemiology and Biostatistics Program, National Cancer Institute, 6130 Executive Boulevard, Bethesda, Maryland, 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 180 EP - 186 VL - 80 IS - 2 Pt 1 SN - 0013-9351, 0013-9351 KW - Pesticides KW - 0 KW - Index Medicus KW - Sex Factors KW - Humans KW - Continental Population Groups KW - Cohort Studies KW - Adult KW - Professional Competence KW - Bias (Epidemiology) KW - Male KW - Female KW - Risk Assessment KW - Agriculture KW - Occupational Exposure -- statistics & numerical data UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69651529?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+research&rft.atitle=Characteristics+of+persons+who+self-reported+a+high+pesticide+exposure+event+in+the+Agricultural+Health+Study.&rft.au=Alavanja%2C+M+C%3BSandler%2C+D+P%3BMcDonnell%2C+C+J%3BMage%2C+D+T%3BKross%2C+B+C%3BRowland%2C+A+S%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1999-02-01&rft.volume=80&rft.issue=2+Pt+1&rft.spage=180&rft.isbn=&rft.btitle=&rft.title=Environmental+research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. AN - 69629369; 10080601 AB - The incidence of secondary leukemia after epipodophyllotoxin treatment and the relationship between epipodophyllotoxin cumulative dose and risk are not well characterized. The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) has developed a monitoring plan to obtain reliable estimates of the risk of secondary leukemia after epipodophyllotoxin treatment. Twelve NCI-supported cooperative group clinical trials were identified that use epipodophyllotoxins at low ( or =3.0 g/m2 etoposide) cumulative doses. Cases of secondary leukemia (including treatment-related myelodysplastic syndrome) occurring on these trials have been reported to CTEP, as has duration of follow-up for all patients, thereby allowing calculation of cumulative 6-year incidence rates of secondary leukemia for each etoposide dose group. The calculated cumulative 6-year risks for development of secondary leukemia for the low, moderate, and higher cumulative dose groups were 3.3%, (95% upper confidence bound of 5.9%), 0.7% (95% upper confidence bound of 1.6%), and 2.2%, (95% upper confidence bound of 4.6%), respectively. Within the context of the epipodophyllotoxin cumulative dose range and schedules of administration encompassed by the monitoring plan regimens, and within the context of multiagent chemotherapy regimens that include alkylating agents, doxorubicin, and other agents, factors other than epipodophyllotoxin cumulative dose seem to be of primary importance in determining the risk of secondary leukemia. Data obtained by the CTEP secondary leukemia monitoring plan support the relative safety of using epipodophyllotoxins according to the therapeutic plans outlined in the monitored protocols. JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology AU - Smith, M A AU - Rubinstein, L AU - Anderson, J R AU - Arthur, D AU - Catalano, P J AU - Freidlin, B AU - Heyn, R AU - Khayat, A AU - Krailo, M AU - Land, V J AU - Miser, J AU - Shuster, J AU - Vena, D AD - National Cancer Institute, Bethesda, MD 20892, USA. smithm@ctep.nci.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 569 EP - 577 VL - 17 IS - 2 SN - 0732-183X, 0732-183X KW - Antineoplastic Agents, Phytogenic KW - 0 KW - Etoposide KW - 6PLQ3CP4P3 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Clinical Trials as Topic KW - Child KW - Child, Preschool KW - Infant KW - Risk Factors KW - Adult KW - Drug Monitoring KW - Follow-Up Studies KW - Adolescent KW - Female KW - Male KW - Leukemia -- chemically induced KW - Antineoplastic Agents, Phytogenic -- adverse effects KW - Antineoplastic Agents, Phytogenic -- therapeutic use KW - Etoposide -- therapeutic use KW - Etoposide -- adverse effects KW - Myelodysplastic Syndromes -- chemically induced KW - Neoplasms, Second Primary -- chemically induced UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69629369?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.atitle=Secondary+leukemia+or+myelodysplastic+syndrome+after+treatment+with+epipodophyllotoxins.&rft.au=Smith%2C+M+A%3BRubinstein%2C+L%3BAnderson%2C+J+R%3BArthur%2C+D%3BCatalano%2C+P+J%3BFreidlin%2C+B%3BHeyn%2C+R%3BKhayat%2C+A%3BKrailo%2C+M%3BLand%2C+V+J%3BMiser%2C+J%3BShuster%2C+J%3BVena%2C+D&rft.aulast=Smith&rft.aufirst=M&rft.date=1999-02-01&rft.volume=17&rft.issue=2&rft.spage=569&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+oncology+%3A+official+journal+of+the+American+Society+of+Clinical+Oncology&rft.issn=0732183X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-01 N1 - Date created - 1999-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Development of TGF-beta resistance during malignant progression. AN - 69614947; 10071951 AB - Transforming growth factor-beta (TGF-beta) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiation as well as a number of basic physiological functions. The effects of TGF-beta are critically dependent on the expression and distribution of a family of TGF-beta receptors, the TGF-beta types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. The coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-beta RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-beta RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-beta RII gene may be a very critical step in the pathway of carcinogenesis. JF - Archives of pharmacal research AU - Kim, Y S AU - Yi, Y AU - Choi, S G AU - Kim, S J AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 1 EP - 8 VL - 22 IS - 1 SN - 0253-6269, 0253-6269 KW - Transforming Growth Factor beta KW - 0 KW - Receptor, Epidermal Growth Factor KW - EC 2.7.10.1 KW - Index Medicus KW - Animals KW - Receptor, Epidermal Growth Factor -- metabolism KW - Humans KW - Disease Progression KW - Receptor, Epidermal Growth Factor -- physiology KW - Mutation KW - Transforming Growth Factor beta -- physiology KW - Neoplasms -- pathology KW - Transforming Growth Factor beta -- genetics KW - Transforming Growth Factor beta -- metabolism KW - Neoplasms -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69614947?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Archives+of+pharmacal+research&rft.atitle=Development+of+TGF-beta+resistance+during+malignant+progression.&rft.au=Kim%2C+Y+S%3BYi%2C+Y%3BChoi%2C+S+G%3BKim%2C+S+J&rft.aulast=Kim&rft.aufirst=Y&rft.date=1999-02-01&rft.volume=22&rft.issue=1&rft.spage=1&rft.isbn=&rft.btitle=&rft.title=Archives+of+pharmacal+research&rft.issn=02536269&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-01 N1 - Date created - 1999-07-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analysis of the degradation function of Mdm2. AN - 69614051; 10074902 AB - Degradation of the p53 tumor suppressor protein has been shown to be regulated by Mdm2. In this study, we identify regions of Mdm2 that are not required for p53 binding but are essential for degradation. Mdm2 mutants lacking these regions function in a dominant negative fashion, stabilizing endogenous p53 in cells by interfering with the degradative function of the endogenous Mdm2. p53 protein stabilized in this way does not strongly enhance the expression of p21(Waf1/Cip1), the product of a p53-responsive gene, supporting the model in which binding of Mdm2 to the NH2-terminal domain of p53 inhibits interaction with other components of the basal transcriptional machinery. Interestingly, COOH-terminal truncations of Mdm2 that retain p53 binding but fail to mediate its degradation are also stabilized themselves. Because Mdm2, like p53, is normally an unstable protein that is degraded through the proteasome, this result suggests a direct link between the regulation of Mdm2 and p53 stability. JF - Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research AU - Kubbutat, M H AU - Ludwig, R L AU - Levine, A J AU - Vousden, K H AD - ABL Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 87 EP - 92 VL - 10 IS - 2 SN - 1044-9523, 1044-9523 KW - Arid4a protein, mouse KW - 0 KW - Carrier Proteins KW - Cell Cycle Proteins KW - DNA-Binding Proteins KW - E2F Transcription Factors KW - Luminescent Proteins KW - Nuclear Proteins KW - Proto-Oncogene Proteins KW - Retinoblastoma Protein KW - Retinoblastoma-Binding Protein 1 KW - Transcription Factor DP1 KW - Transcription Factors KW - Tumor Suppressor Protein p53 KW - Green Fluorescent Proteins KW - 147336-22-9 KW - MDM2 protein, human KW - EC 2.3.2.27 KW - Mdm2 protein, mouse KW - Proto-Oncogene Proteins c-mdm2 KW - Index Medicus KW - Animals KW - Transcription Factors -- metabolism KW - Humans KW - Luminescent Proteins -- metabolism KW - Mice KW - Precipitin Tests KW - Mutagenesis KW - Blotting, Western KW - Transfection KW - Retinoblastoma Protein -- metabolism KW - Point Mutation KW - Cell Line KW - Proto-Oncogene Proteins -- metabolism KW - Proto-Oncogene Proteins -- genetics KW - Tumor Suppressor Protein p53 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69614051?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.atitle=Analysis+of+the+degradation+function+of+Mdm2.&rft.au=Kubbutat%2C+M+H%3BLudwig%2C+R+L%3BLevine%2C+A+J%3BVousden%2C+K+H&rft.aulast=Kubbutat&rft.aufirst=M&rft.date=1999-02-01&rft.volume=10&rft.issue=2&rft.spage=87&rft.isbn=&rft.btitle=&rft.title=Cell+growth+%26+differentiation+%3A+the+molecular+biology+journal+of+the+American+Association+for+Cancer+Research&rft.issn=10449523&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-21 N1 - Date created - 1999-05-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The extracellular versus intracellular mechanisms of inhibition of TCR-triggered activation in thymocytes by adenosine under conditions of inhibited adenosine deaminase. AN - 69611994; 10069416 AB - The absence or low levels of adenosine deaminase (ADA) in humans result in severe combined immunodeficiency (SCID), which is characterized by hypoplastic thymus, T lymphocyte depletion and autoimmunity. Deficiency of ADA causes increased levels of both intracellular and extracellular adenosine, although only the intracellular lymphotoxicity of accumulated adenosine is considered in the pathogenesis of ADA SCID. It is shown that extracellular but not intracellular adenosine selectively inhibits TCR-triggered up-regulation of activation markers and apoptotic events in thymocytes under conditions of ADA deficiency. The effects of intracellular adenosine are dissociated from effects of extracellular adenosine in experiments using an adenosine transporter blocker. We found that prevention of toxicity of intracellular adenosine led to survival of TCR-cross-linked thymocytes in long-term (4 days) assays, but it was not sufficient for normal T cell differentiation under conditions of inhibited ADA. Surviving TCR-cross-linked thymocytes had a non-activated phenotype due to extracellular adenosine-mediated, TCR-antagonizing signaling. Taken together the data suggest that both intracellular toxicity and signaling by extracellular adenosine may contribute to pathogenesis of ADA SCID. Accordingly, extracellular adenosine may act on thymocytes, which survived intracellular toxicity of adenosine during ADA deficiency by counteracting TCR signaling. This, in turn, could lead to failure of positive and negative selection of thymocytes, and to additional elimination of thymocytes or autoimmunity of surviving T cells. JF - International immunology AU - Apasov, S G AU - Sitkovsky, M V AD - Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 179 EP - 189 VL - 11 IS - 2 SN - 0953-8178, 0953-8178 KW - Adenosine Deaminase Inhibitors KW - 0 KW - Antigens, CD3 KW - Receptors, Antigen, T-Cell KW - Adenosine Deaminase KW - EC 3.5.4.4 KW - GTP-Binding Proteins KW - EC 3.6.1.- KW - Adenosine KW - K72T3FS567 KW - Index Medicus KW - Adenosine Deaminase -- metabolism KW - Thymus Gland -- cytology KW - Animals KW - Apoptosis KW - Antigens, CD3 -- metabolism KW - GTP-Binding Proteins -- metabolism KW - Biological Transport KW - Mice KW - Mice, Transgenic KW - GTP-Binding Proteins -- immunology KW - Mice, Inbred DBA KW - Lymphocyte Activation -- drug effects KW - Adenosine -- pharmacology KW - Severe Combined Immunodeficiency -- enzymology KW - Receptors, Antigen, T-Cell -- immunology KW - T-Lymphocytes -- immunology KW - Severe Combined Immunodeficiency -- immunology KW - Adenosine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69611994?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+immunology&rft.atitle=The+extracellular+versus+intracellular+mechanisms+of+inhibition+of+TCR-triggered+activation+in+thymocytes+by+adenosine+under+conditions+of+inhibited+adenosine+deaminase.&rft.au=Apasov%2C+S+G%3BSitkovsky%2C+M+V&rft.aulast=Apasov&rft.aufirst=S&rft.date=1999-02-01&rft.volume=11&rft.issue=2&rft.spage=179&rft.isbn=&rft.btitle=&rft.title=International+immunology&rft.issn=09538178&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-08-17 N1 - Date created - 1999-08-17 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Atypical ductular proliferation and its inhibition by transforming growth factor beta1 in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease. AN - 69607713; 10068199 AB - Many acute and chronic liver diseases are often associated with atypical ductular proliferation (ADP). These ADPs have gained increasing interest since a number of recent observations suggest that ADPs may represent progenies of the putative liver stem cell compartment. In this study, we show that feeding mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) results in persistent proliferation of primitive ductules with poorly defined lumens. Similar to oval cell proliferation in other rodent models as well as in various human liver diseases, DDC-induced ADP originated from the portal tract, spread into the hepatic lobule, and was associated closely with appearance of hepatocytes harboring an antigen (A6), which normally is expressed in biliary epithelium. Furthermore, DDC treatment severely inhibited the regenerative capacity of mice after partial hepatectomy. The development of ADP was selectively blocked in DDC-fed TGF-beta1 transgenic mice producing active TGF-beta1 in the liver and no accumulation of new hepatocytes expressing the A6 antigen was observed. Moreover, the transforming growth factor beta1 (TGF-beta1) transgenic mice did not survive beyond 3 weeks from starting the DDC-containing diet. The results suggest that persistent activation of the hepatic stem cell compartment is essential for liver regeneration in the DDC model and that active TGF-beta1 may negatively control activation of stem cells in the liver. These data further emphasize the relevance of the DDC model as an experimental tool for studying chronic liver diseases. JF - Laboratory investigation; a journal of technical methods and pathology AU - Preisegger, K H AU - Factor, V M AU - Fuchsbichler, A AU - Stumptner, C AU - Denk, H AU - Thorgeirsson, S S AD - Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 103 EP - 109 VL - 79 IS - 2 SN - 0023-6837, 0023-6837 KW - Transforming Growth Factor beta KW - 0 KW - Dicarbethoxydihydrocollidine KW - 632-93-9 KW - Index Medicus KW - Liver Regeneration -- drug effects KW - Animals KW - Liver -- pathology KW - Chemical and Drug Induced Liver Injury KW - Cell Division -- drug effects KW - Hepatectomy -- methods KW - Disease Models, Animal KW - Mice KW - Epithelial Cells -- pathology KW - Liver -- drug effects KW - Common Bile Duct KW - Ligation KW - Chronic Disease KW - Mice, Transgenic -- genetics KW - Transforming Growth Factor beta -- pharmacology KW - Bile Ducts, Intrahepatic -- drug effects KW - Liver Diseases, Alcoholic -- pathology KW - Bile Ducts, Intrahepatic -- pathology KW - Transforming Growth Factor beta -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607713?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.atitle=Atypical+ductular+proliferation+and+its+inhibition+by+transforming+growth+factor+beta1+in+the+3%2C5-diethoxycarbonyl-1%2C4-dihydrocollidine+mouse+model+for+chronic+alcoholic+liver+disease.&rft.au=Preisegger%2C+K+H%3BFactor%2C+V+M%3BFuchsbichler%2C+A%3BStumptner%2C+C%3BDenk%2C+H%3BThorgeirsson%2C+S+S&rft.aulast=Preisegger&rft.aufirst=K&rft.date=1999-02-01&rft.volume=79&rft.issue=2&rft.spage=103&rft.isbn=&rft.btitle=&rft.title=Laboratory+investigation%3B+a+journal+of+technical+methods+and+pathology&rft.issn=00236837&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-01 N1 - Date created - 1999-04-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Actions of intrathecal diphtheria toxin-substance P fusion protein on models of persistent pain. AN - 69607607; 10068170 AB - Substance P (SP) plays a central role in the transduction of second messenger signals from primary afferent nociceptive terminals to second-order neurons in the spinal cord. We have tested a recombinant engineered diphtheria toxin/SP fusion protein (DAB389SP) in acute and chronic pain models in the rat. DAB389SP binds to the SP receptor (SPR) and is internalized and kills SPR-expressing cells by blocking cellular protein synthesis. DAB389SP delivery was by intrathecal infusion, of varying duration, at the lumbar level. In the chronic constriction injury model of neuropathic pain a significant reduction in mechanically induced hyperalgesia was obtained. This effect was less marked in an acute carageenan inflammation model. Although other pain characteristics (mechano-allodynia, cold-allodynia, and heat-hyperalgesia) showed some improvement, these were less pronounced. Immunocytochemistry revealed a toxin-induced reduction in lamina I, of SPR and of NMDA NR1 subunit receptor expressing neurons, and of c-Fos, an inducible molecular marker of persistent nociceptive activity. The use of cytotoxic fusion proteins to target specific cell types may be of considerable benefit in the study of nociception and the treatment of chronic pain. JF - Pain AU - Benoliel, R AU - Eliav, E AU - Mannes, A J AU - Caudle, R M AU - Leeman, S AU - Iadarola, M J AD - Neuronal Gene Expression Unit, Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4410, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 243 EP - 253 VL - 79 IS - 2-3 SN - 0304-3959, 0304-3959 KW - Diphtheria Toxin KW - 0 KW - Recombinant Fusion Proteins KW - Substance P KW - 33507-63-0 KW - Carrageenan KW - 9000-07-1 KW - Index Medicus KW - Acute Disease KW - Animals KW - Inflammation -- chemically induced KW - Pain Measurement KW - Inflammation -- drug therapy KW - Sciatic Nerve -- physiopathology KW - Rats KW - Rats, Sprague-Dawley KW - Hyperalgesia -- pathology KW - Constriction, Pathologic -- physiopathology KW - Hyperalgesia -- physiopathology KW - Injections, Spinal KW - Chronic Disease KW - Immunohistochemistry KW - Male KW - Inflammation -- pathology KW - Pain -- drug therapy KW - Pain -- pathology KW - Diphtheria Toxin -- genetics KW - Substance P -- genetics KW - Recombinant Fusion Proteins -- therapeutic use KW - Recombinant Fusion Proteins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607607?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Pain&rft.atitle=Actions+of+intrathecal+diphtheria+toxin-substance+P+fusion+protein+on+models+of+persistent+pain.&rft.au=Benoliel%2C+R%3BEliav%2C+E%3BMannes%2C+A+J%3BCaudle%2C+R+M%3BLeeman%2C+S%3BIadarola%2C+M+J&rft.aulast=Benoliel&rft.aufirst=R&rft.date=1999-02-01&rft.volume=79&rft.issue=2-3&rft.spage=243&rft.isbn=&rft.btitle=&rft.title=Pain&rft.issn=03043959&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-21 N1 - Date created - 1999-06-21 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes. AN - 69607496; 10067811 AB - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption of normal hormone signaling pathways, reproductive and developmental effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen. Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and adverse health effects. In this study, we examined the expression of CYP1B1 in human peripheral blood lymphocytes of unexposed individuals using a quantitative reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1-5 days of culture resulted in a peak induction of CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied greatly among different individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1 exhibits variable constitutive expression and is inducible in vitro by TCDD in human lymphocytes and that the magnitude of induction varies within the population. These data define the suitability of CYP1B1 for use as a mechanistically based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromatic hydrocarbon receptor. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Spencer, D L AU - Masten, S A AU - Lanier, K M AU - Yang, X AU - Grassman, J A AU - Miller, C R AU - Sutter, T R AU - Lucier, G W AU - Walker, N J AD - Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 139 EP - 146 VL - 8 IS - 2 SN - 1055-9965, 1055-9965 KW - Biomarkers KW - 0 KW - Biomarkers, Tumor KW - Environmental Pollutants KW - Estrogens, Catechol KW - Mitogens KW - Polychlorinated Dibenzodioxins KW - Estradiol KW - 4TI98Z838E KW - RNA KW - 63231-63-0 KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - 4-hydroxyestradiol KW - C3ZO03450E KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Dose-Response Relationship, Drug KW - Humans KW - Estrogens, Catechol -- biosynthesis KW - RNA -- analysis KW - Lymphocyte Activation -- drug effects KW - Leukocytes, Mononuclear -- enzymology KW - Estradiol -- analogs & derivatives KW - Molecular Epidemiology KW - Gene Expression Regulation, Enzymologic -- drug effects KW - Biomarkers -- analysis KW - Adult KW - Biomarkers, Tumor -- analysis KW - Environmental Exposure KW - Estradiol -- biosynthesis KW - Middle Aged KW - Leukocytes, Mononuclear -- drug effects KW - Male KW - Female KW - RNA -- genetics KW - Cytochrome P-450 Enzyme System -- analysis KW - Cytochrome P-450 Enzyme System -- genetics KW - Polychlorinated Dibenzodioxins -- adverse effects KW - Lymphocytes -- enzymology KW - Cytochrome P-450 Enzyme System -- drug effects KW - Lymphocytes -- drug effects KW - Environmental Pollutants -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607496?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Quantitative+analysis+of+constitutive+and+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin-induced+cytochrome+P450+1B1+expression+in+human+lymphocytes.&rft.au=Spencer%2C+D+L%3BMasten%2C+S+A%3BLanier%2C+K+M%3BYang%2C+X%3BGrassman%2C+J+A%3BMiller%2C+C+R%3BSutter%2C+T+R%3BLucier%2C+G+W%3BWalker%2C+N+J&rft.aulast=Spencer&rft.aufirst=D&rft.date=1999-02-01&rft.volume=8&rft.issue=2&rft.spage=139&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-28 N1 - Date created - 1999-04-28 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Merkel cell carcinoma and melanoma: etiological similarities and differences. AN - 69607457; 10067813 AB - Merkel cell carcinoma (MCC) of the skin and cutaneous malignant melanoma can now be compared epidemiologically through the use of population-based data not previously available for MCC. The results may provide new clues to etiology. In this study, United States data covered by the Surveillance, Epidemiology, and End Results (SEER) Program were from nine areas of the United States (approximately 10% of the population). In 1986-1994, 425 cases of MCC were registered. The annual age-adjusted incidence per 100,000 of MCC was 0.23 for whites and 0.01 for blacks; among whites, the ratio of melanoma to MCC was approximately 65 to 1. Only 5% of MCC occurred before age 50, unlike the lifelong risk of nodular and superficial spreading melanoma. Regional incidence rates of both cancers increased similarly with increasing sun exposure as measured by the UVB solar index. The most sun-exposed anatomical site, the face, was the location of 36% of MCC but only 14% of melanoma. Both cancers increased in frequency and aggressiveness after immunosuppression and organ transplantation (36 cases from the Cincinnati Transplant Tumor registry and 12 from published case reports) and after B-cell neoplasia (5 cases in this study; 13 from case series in the literature). The SEER data contained reports of six patients with both types of cancer; 5 melanomas before the diagnosis of MCC and 1 after diagnosis. MCC and melanoma are similarly related to sun exposure and immunosuppression, but they differ markedly from one another in their distributions by age, race, and anatomical site, especially the face. JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology AU - Miller, R W AU - Rabkin, C S AD - Genetic Epidemiology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-7360, USA. millerr@epndce.nci.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 153 EP - 158 VL - 8 IS - 2 SN - 1055-9965, 1055-9965 KW - Index Medicus KW - Age Factors KW - Neoplasms, Multiple Primary -- epidemiology KW - Sunlight -- adverse effects KW - Humans KW - SEER Program KW - Lymphoma, B-Cell -- epidemiology KW - Aged KW - Facial Neoplasms -- epidemiology KW - Population Surveillance KW - Registries KW - Immunosuppression -- adverse effects KW - Neoplasms, Second Primary -- epidemiology KW - Aged, 80 and over KW - European Continental Ancestry Group KW - Ultraviolet Rays -- adverse effects KW - Environmental Exposure KW - Incidence KW - Middle Aged KW - Organ Transplantation -- adverse effects KW - United States -- epidemiology KW - African Continental Ancestry Group KW - Facial Neoplasms -- etiology KW - Male KW - Female KW - Carcinoma, Merkel Cell -- epidemiology KW - Skin Neoplasms -- etiology KW - Melanoma -- etiology KW - Skin Neoplasms -- epidemiology KW - Carcinoma, Merkel Cell -- etiology KW - Melanoma -- epidemiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607457?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.atitle=Merkel+cell+carcinoma+and+melanoma%3A+etiological+similarities+and+differences.&rft.au=Miller%2C+R+W%3BRabkin%2C+C+S&rft.aulast=Miller&rft.aufirst=R&rft.date=1999-02-01&rft.volume=8&rft.issue=2&rft.spage=153&rft.isbn=&rft.btitle=&rft.title=Cancer+epidemiology%2C+biomarkers+%26+prevention+%3A+a+publication+of+the+American+Association+for+Cancer+Research%2C+cosponsored+by+the+American+Society+of+Preventive+Oncology&rft.issn=10559965&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-28 N1 - Date created - 1999-04-28 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Erratum In: Cancer Epidemiol Biomarkers Prev 1999 May;8(5):485 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Buspirone treatment of alcoholism: age of onset, and cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid concentrations, but not medication treatment, predict return to drinking. AN - 69607334; 10069556 AB - Disturbances in central nervous system serotonin (5-HT) have been implicated in the pathophysiology of alcoholism. To test the hypothesis that increasing 5-HT function could promote treatment compliance, we randomized patients who had completed a 5-week inpatient treatment program for alcoholism to receive either buspirone or placebo for 1 year. Ten of the 49 patients remained in the study for the entire year. The days to relapse did not differ significantly between patients receiving buspirone or placebo. Regardless of the medication, late-onset alcoholics had a longer time to relapse than early-onset alcoholics. Cerebrospinal fluid showed that patients with high concentrations of both the 5-HT metabolite, 5-hydroxyindoleacetic acid, and the dopamine metabolite, homovanillic acid, were more likely to relapse, compared with patients with low concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid. JF - Alcoholism, clinical and experimental research AU - George, D T AU - Rawlings, R AU - Eckardt, M J AU - Phillips, M J AU - Shoaf, S E AU - Linnoila, M AD - Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-1610, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 272 EP - 278 VL - 23 IS - 2 SN - 0145-6008, 0145-6008 KW - Anti-Anxiety Agents KW - 0 KW - Hydroxyindoleacetic Acid KW - 54-16-0 KW - Buspirone KW - TK65WKS8HL KW - Homovanillic Acid KW - X77S6GMS36 KW - Index Medicus KW - Homovanillic Acid -- cerebrospinal fluid KW - Psychiatric Status Rating Scales KW - Double-Blind Method KW - Age of Onset KW - Humans KW - Adult KW - Hydroxyindoleacetic Acid -- cerebrospinal fluid KW - Predictive Value of Tests KW - Middle Aged KW - Recurrence KW - Male KW - Survival Analysis KW - Buspirone -- therapeutic use KW - Alcoholism -- cerebrospinal fluid KW - Anti-Anxiety Agents -- therapeutic use KW - Alcoholism -- psychology KW - Alcoholism -- drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69607334?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Alcoholism%2C+clinical+and+experimental+research&rft.atitle=Buspirone+treatment+of+alcoholism%3A+age+of+onset%2C+and+cerebrospinal+fluid+5-hydroxyindolacetic+acid+and+homovanillic+acid+concentrations%2C+but+not+medication+treatment%2C+predict+return+to+drinking.&rft.au=George%2C+D+T%3BRawlings%2C+R%3BEckardt%2C+M+J%3BPhillips%2C+M+J%3BShoaf%2C+S+E%3BLinnoila%2C+M&rft.aulast=George&rft.aufirst=D&rft.date=1999-02-01&rft.volume=23&rft.issue=2&rft.spage=272&rft.isbn=&rft.btitle=&rft.title=Alcoholism%2C+clinical+and+experimental+research&rft.issn=01456008&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-09 N1 - Date created - 1999-06-09 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gangliosides asymmetrically alter the membrane order in cultured PC-12 cells. AN - 69603989; 10063608 AB - Exogenous gangliosides readily associate with the cell membranes and produce marked effects on cell growth and differentiation. We have studied the effect of bovine brain gangliosides (BBG) on the membrane dynamics of intact cells. The structural and dynamic changes in the cell membrane were monitored by the fluorescence probes DPH, TMA-DPH and laurdan. Incorporation of BBG into the cell membrane decreased the fluorescence intensity, lifetime and the steady state anisotropy of TMA-DPH. Analysis of the time resolved anisotropy decay by wobbling in the cone model revealed that BBG decreased the order parameter, and increased the cone angle without altering the rotational relaxation rate. The fluorescence intensity and lifetime of DPH were unaffected by BBG incorporation, however, a modest increase was observed in the steady state anisotropy. BBG incorporation reduced the total fluorescence intensity of laurdan with pronounced quenching of the 440-nm band. The wavelength sensitivity of generalized polarization of laurdan manifested an ordered liquid crystalline environment of the probe in the cell membrane. BBG incorporation reduced the GP values and augmented the liquid crystalline behavior of the cell membrane. BBG incorporation also influenced the permeability of cell membranes to cations. An influx of Na+ and Ca2+ and an efflux of K+ was observed. The data demonstrate that incorporation of gangliosides into the cell membrane substantially enhances the disorder and hydration of the lipid bilayer region near the exoplasmic surface. The inner core region near the center of the bilayer becomes slightly more ordered and remains highly hydrophobic. Such changes in the structure and dynamics of the membrane could play an important role in modulation of transmembrane signaling events by the gangliosides. JF - Biophysical chemistry AU - Ravichandra, B AU - Joshi, P G AD - Department of Biophysics, National Institute of Mental Health and Neurosciences, Bangalore, India. Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 117 EP - 132 VL - 76 IS - 2 SN - 0301-4622, 0301-4622 KW - Fluorescent Dyes KW - 0 KW - Gangliosides KW - Laurates KW - Membranes, Artificial KW - 2-Naphthylamine KW - CKR7XL41N4 KW - laurdan KW - Y97FBL93VW KW - Index Medicus KW - Animals KW - Anisotropy KW - Brain Chemistry KW - Laurates -- metabolism KW - 2-Naphthylamine -- analogs & derivatives KW - Rats KW - Microscopy, Fluorescence KW - 2-Naphthylamine -- metabolism KW - Cattle KW - Cell Survival -- physiology KW - PC12 Cells KW - Gangliosides -- pharmacology KW - Cell Membrane -- drug effects KW - Cell Membrane -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69603989?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biophysical+chemistry&rft.atitle=Gangliosides+asymmetrically+alter+the+membrane+order+in+cultured+PC-12+cells.&rft.au=Ravichandra%2C+B%3BJoshi%2C+P+G&rft.aulast=Ravichandra&rft.aufirst=B&rft.date=1999-02-01&rft.volume=76&rft.issue=2&rft.spage=117&rft.isbn=&rft.btitle=&rft.title=Biophysical+chemistry&rft.issn=03014622&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-04-13 N1 - Date created - 1999-04-13 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - The role of interindividual variation in human carcinogenesis. AN - 69600321; 10064330 AB - The process of chemical carcinogenesis is a complex multistage process initiated by DNA damage in growth control genes. Carcinogens enter the body from a variety of sources, but most require metabolic activation before they can damage DNA. There are multiple protective processes that include detoxification and conjugation, DNA repair and programmed cell death. Most of these functions exhibit wide interindividual variation in the population and thus are thought to affect cancer risk. The role of gene-environment interactions is being explored, and current data indicate that genetic susceptibilities can modify carcinogen exposures from the diet and tobacco smoking, although much more data exist for the latter. This review addresses the relationships of human carcinogenesis to these interindividual differences of phase I, phase II and DNA repair enzymes. JF - The Journal of nutrition AU - Lai, C AU - Shields, P G AD - Molecular Epidemiology Section, Laboratory of Human Carcinogenesis, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 552S EP - 555S VL - 129 IS - 2S Suppl SN - 0022-3166, 0022-3166 KW - Carcinogens KW - 0 KW - Index Medicus KW - Carcinogens -- metabolism KW - Polymorphism, Genetic KW - Risk Factors KW - Humans KW - Genetic Variation KW - Neoplasms -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69600321?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=The+role+of+interindividual+variation+in+human+carcinogenesis.&rft.au=Lai%2C+C%3BShields%2C+P+G&rft.aulast=Lai&rft.aufirst=C&rft.date=1999-02-01&rft.volume=129&rft.issue=2S+Suppl&rft.spage=552S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-11 N1 - Date created - 1999-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Diet, genetic susceptibility and human cancer etiology. AN - 69597935; 10064331 AB - There is evidence that high penetrance hereditary genes cause a number of relatively uncommon tumors in the familial setting, whereas common cancers are influenced by multiple loci that alter susceptibility to cancer and other conditions. The latter category of genes are involved in the metabolism of carcinogens (activation, detoxification) as well as those that interact with dietary exposure. This paper will consider some of the basic principles in studying susceptibility genes and provide a few examples in which they interact with dietary components. JF - The Journal of nutrition AU - Sinha, R AU - Caporaso, N AD - Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 556S EP - 559S VL - 129 IS - 2S Suppl SN - 0022-3166, 0022-3166 KW - Carcinogens KW - 0 KW - Vitamin D KW - 1406-16-2 KW - Ethanol KW - 3K9958V90M KW - Alcohol Dehydrogenase KW - EC 1.1.1.1 KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Meat KW - Humans KW - Genetic Predisposition to Disease KW - Diet KW - Neoplasms -- genetics KW - Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69597935?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+nutrition&rft.atitle=Diet%2C+genetic+susceptibility+and+human+cancer+etiology.&rft.au=Sinha%2C+R%3BCaporaso%2C+N&rft.aulast=Sinha&rft.aufirst=R&rft.date=1999-02-01&rft.volume=129&rft.issue=2S+Suppl&rft.spage=556S&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+nutrition&rft.issn=00223166&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-11 N1 - Date created - 1999-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Is human thioredoxin monomeric or dimeric? AN - 69593898; 10048336 AB - We have examined the molecular weight and rotational correlation time of human thioredoxin by analytical ultracentrifugation and NMR spectroscopy, respectively. Two variants of human thioredoxin were studied, namely human thioredoxin identical in amino acid sequence to the one whose NMR structure we previously determined (C62A, C69A, C73A, M74T) and human thioredoxin (C62A, C69A, C73A, M74) containing the wild-type amino acid methionine at position 74. In both cases, the experimental data indicate that the predominant species is monomeric and we find no evidence for the existence of a well-defined dimeric form as was observed in the recently reported crystal structure (Weichsel et al., 1996) of human thioredoxin and the C73S mutant. JF - Protein science : a publication of the Protein Society AU - Gronenborn, A M AU - Clore, G M AU - Louis, J M AU - Wingfield, P T AD - Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. gronenborn@vger.niddk.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 426 EP - 429 VL - 8 IS - 2 SN - 0961-8368, 0961-8368 KW - Threonine KW - 2ZD004190S KW - Thioredoxins KW - 52500-60-4 KW - Methionine KW - AE28F7PNPL KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Humans KW - Methionine -- analysis KW - Threonine -- analysis KW - Ultracentrifugation KW - Protein Conformation KW - Magnetic Resonance Spectroscopy KW - Thioredoxins -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69593898?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.atitle=Is+human+thioredoxin+monomeric+or+dimeric%3F&rft.au=Gronenborn%2C+A+M%3BClore%2C+G+M%3BLouis%2C+J+M%3BWingfield%2C+P+T&rft.aulast=Gronenborn&rft.aufirst=A&rft.date=1999-02-01&rft.volume=8&rft.issue=2&rft.spage=426&rft.isbn=&rft.btitle=&rft.title=Protein+science+%3A+a+publication+of+the+Protein+Society&rft.issn=09618368&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-05-06 N1 - Date created - 1999-05-06 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Biochemistry. 1989 Nov 14;28(23):8972-9 [2690953] Biochemistry. 1990 Aug 14;29(32):7387-401 [2223770] J Biomol NMR. 1992 Sep;2(5):431-45 [1422155] J Mol Biol. 1993 Mar 20;230(2):364-72 [8464050] Biochemistry. 1997 Nov 18;36(46):13979-88 [9369469] Structure. 1996 Jun 15;4(6):735-51 [8805557] J Biomol NMR. 1996 Oct;8(3):273-84 [8953218] Protein Sci. 1997 Aug;6(8):1653-60 [9260278] Structure. 1994 Jun 15;2(6):503-22 [7922028] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Corneal endothelial deposits in children positive for human immunodeficiency virus receiving rifabutin prophylaxis for Mycobacterium avium complex bacteremia. AN - 69590534; 10030558 AB - To assess the potential ocular effects of prophylactic administration of rifabutin in children with symptomatic human immunodeficiency virus (HIV) infection and CD4 counts less than 50 cells per mm3. Twenty-five children with HIV infection were enrolled in a phase I-II study of prophylactic administration of systemic rifabutin for prevention of disseminated Mycobacterium avium complex infection and monitored prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. The dose of rifabutin ranged from 5.0 mg to 15.0 mg per kg, and the median ophthalmic follow-up was 24 months. During the study period, six of the children receiving rifabutin prophylaxis for M. avium complex developed unusual bilateral, initially peripheral, stellate, corneal endothelial deposits without associated uveitis. Review of serial corneal drawings and photographs showed an increase in the number of corneal deposits with continued administration of rifabutin. The duration of rifabutin treatment (P = .017) and follow-up (P = .0011) was significantly longer in patients who developed these corneal endothelial changes. Corneal endothelial deposits should be considered a potential side effect of rifabutin therapy. To date, these findings have not been sight threatening. JF - American journal of ophthalmology AU - Smith, J A AU - Mueller, B U AU - Nussenblatt, R B AU - Whitcup, S M AD - Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1858, USA. jmas@box-j.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 164 EP - 169 VL - 127 IS - 2 SN - 0002-9394, 0002-9394 KW - Anti-Bacterial Agents KW - 0 KW - Rifabutin KW - 1W306TDA6S KW - Abridged Index Medicus KW - Index Medicus KW - AIDS/HIV KW - Prospective Studies KW - Cell Count KW - Humans KW - AIDS-Related Opportunistic Infections -- microbiology KW - Child KW - AIDS-Related Opportunistic Infections -- prevention & control KW - Adolescent KW - Visual Acuity KW - Male KW - Female KW - Child, Preschool KW - Corneal Diseases -- chemically induced KW - Rifabutin -- adverse effects KW - Anti-Bacterial Agents -- therapeutic use KW - Bacteremia -- prevention & control KW - Anti-Bacterial Agents -- adverse effects KW - Rifabutin -- therapeutic use KW - HIV Seropositivity -- complications KW - Bacteremia -- microbiology KW - Endothelium, Corneal -- drug effects KW - Mycobacterium avium-intracellulare Infection -- prevention & control KW - Endothelium, Corneal -- pathology KW - Antibiotic Prophylaxis KW - Corneal Diseases -- pathology KW - Mycobacterium avium-intracellulare Infection -- microbiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69590534?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+ophthalmology&rft.atitle=Corneal+endothelial+deposits+in+children+positive+for+human+immunodeficiency+virus+receiving+rifabutin+prophylaxis+for+Mycobacterium+avium+complex+bacteremia.&rft.au=Smith%2C+J+A%3BMueller%2C+B+U%3BNussenblatt%2C+R+B%3BWhitcup%2C+S+M&rft.aulast=Smith&rft.aufirst=J&rft.date=1999-02-01&rft.volume=127&rft.issue=2&rft.spage=164&rft.isbn=&rft.btitle=&rft.title=American+journal+of+ophthalmology&rft.issn=00029394&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-26 N1 - Date created - 1999-02-26 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Ophthalmol. 2000 Mar;129(3):410-1 [10755956] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. AN - 69579014; 9989554 AB - There has been speculation in the literature about a link between fluoxetine use and suicidal behavior. The authors of this study hypothesized that there is no elevation in risk of suicidal behavior associated with use of fluoxetine. The data come from the National Institute of Mental Health Collaborative Depression Study, a prospective, naturalistic follow-up of persons who presented for treatment of affective disorders. The analyses included data on 643 subjects who were followed up after fluoxetine was approved by the Food and Drug Administration in December 1987 for the treatment of depression. Nearly 30% (N = 185) of the study group was treated with fluoxetine at some point during the follow-up period. Relative to the other subjects, those who were subsequently treated with fluoxetine had onset of affective illness at a younger age and, after intake into the study and before 1988, had elevated rates of suicide attempts before fluoxetine treatment. A mixed-effects survival analysis that incorporated treatment exposure time, multiple treatment trials, and multiple suicide attempts per subject showed that relative to no treatment, use of fluoxetine and use of other somatic antidepressants were associated with nonsignificant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with elevated risk, and each suicide attempt after intake into the Collaborative Depression Study was associated with a marginally significant increase in risk of suicidal behavior. The results do not support the speculation that fluoxetine increases the risk of suicide. Rather, there was a nonsignificant reduction in risk of suicidal behavior among patients treated with fluoxetine, even though those subjects were more severely ill before treatment with fluoxetine. JF - The American journal of psychiatry AU - Leon, A C AU - Keller, M B AU - Warshaw, M G AU - Mueller, T I AU - Solomon, D A AU - Coryell, W AU - Endicott, J AD - NIMH Collaborative Depression Study, USA. acleon@mail.med.cornell.edu Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 195 EP - 201 VL - 156 IS - 2 SN - 0002-953X, 0002-953X KW - Antidepressive Agents KW - 0 KW - Serotonin Uptake Inhibitors KW - Fluoxetine KW - 01K63SUP8D KW - Abridged Index Medicus KW - Index Medicus KW - Severity of Illness Index KW - Drug Administration Schedule KW - Age of Onset KW - Suicide, Attempted -- psychology KW - Humans KW - Antidepressive Agents -- adverse effects KW - Prospective Studies KW - Antidepressive Agents -- administration & dosage KW - Suicide, Attempted -- statistics & numerical data KW - Risk Factors KW - Adult KW - Treatment Outcome KW - Antidepressive Agents -- therapeutic use KW - Follow-Up Studies KW - Female KW - Male KW - Survival Analysis KW - Fluoxetine -- adverse effects KW - Serotonin Uptake Inhibitors -- administration & dosage KW - Depressive Disorder -- psychology KW - Serotonin Uptake Inhibitors -- therapeutic use KW - Fluoxetine -- administration & dosage KW - Fluoxetine -- therapeutic use KW - Depressive Disorder -- drug therapy KW - Suicide -- statistics & numerical data KW - Suicide -- psychology KW - Serotonin Uptake Inhibitors -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69579014?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Prospective+study+of+fluoxetine+treatment+and+suicidal+behavior+in+affectively+ill+subjects.&rft.au=Leon%2C+A+C%3BKeller%2C+M+B%3BWarshaw%2C+M+G%3BMueller%2C+T+I%3BSolomon%2C+D+A%3BCoryell%2C+W%3BEndicott%2C+J&rft.aulast=Leon&rft.aufirst=A&rft.date=1999-02-01&rft.volume=156&rft.issue=2&rft.spage=195&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas. AN - 69577023; 10027343 AB - To examine the association between gallstones and cholecystectomy, we conducted a nationwide population-based cohort study in Denmark. Patients with a discharge diagnosis of gallstones from 1977 to 1989 were identified from the Danish National Registry of Patients and followed up for cancer occurrence until death or the end of 1993 by record linkage to the Danish Cancer Registry. Included in the cohort were 60 176 patients, with 471 450 person-years of follow-up. Cancer risks were estimated by standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) stratified by years of follow-up and by cholecystectomy status. Among patients without cholecystectomy, the risks at 5 or more years of follow-up were significantly elevated for cancers of liver (SIR = 2.0, CI = 1.2-3.1) and gallbladder (SIR = 2.7, CI = 1.5-4.4) and near unity for cancers of extrahepatic bile duct (SIR = 1.1), ampulla of Vater (SIR = 1.0) and pancreas (SIR = 1.1). The excess risk of liver cancer was seen only among patients with a history of hepatic disease. Among cholecystectomy patients, the risks at 5 or more years of follow-up declined for cancers of liver (SIR = 1.1) and extrahepatic bile duct (SIR = 0.7), but were elevated for cancers of ampulla of Vater (SIR = 2.0, CI = 1.0-3.7) and pancreas (SIR = 1.3, CI = 1.1-1.6). These findings confirm that gallstone disease increases the risk of gallbladder cancer, whereas cholecystectomy appears to increase the risk of cancers of ampulla of Vater and pancreas. Further research is needed to clarify the carcinogenic risks associated with gallstones and cholecystectomy and to define the mechanisms involved. JF - British journal of cancer AU - Chow, W H AU - Johansen, C AU - Gridley, G AU - Mellemkjaer, L AU - Olsen, J H AU - Fraumeni, J F AD - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892-7182, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 640 EP - 644 VL - 79 IS - 3-4 SN - 0007-0920, 0007-0920 KW - Index Medicus KW - Humans KW - Cohort Studies KW - Denmark -- epidemiology KW - Incidence KW - Aged KW - Middle Aged KW - Male KW - Female KW - Risk Assessment KW - Registries KW - Gallbladder Neoplasms -- epidemiology KW - Biliary Tract Neoplasms -- epidemiology KW - Cholelithiasis -- surgery KW - Cholelithiasis -- complications KW - Biliary Tract Neoplasms -- etiology KW - Gallbladder Neoplasms -- etiology KW - Pancreatic Neoplasms -- epidemiology KW - Liver Neoplasms -- epidemiology KW - Liver Neoplasms -- etiology KW - Cholecystectomy -- adverse effects KW - Pancreatic Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69577023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=British+journal+of+cancer&rft.atitle=Gallstones%2C+cholecystectomy+and+risk+of+cancers+of+the+liver%2C+biliary+tract+and+pancreas.&rft.au=Chow%2C+W+H%3BJohansen%2C+C%3BGridley%2C+G%3BMellemkjaer%2C+L%3BOlsen%2C+J+H%3BFraumeni%2C+J+F&rft.aulast=Chow&rft.aufirst=W&rft.date=1999-02-01&rft.volume=79&rft.issue=3-4&rft.spage=640&rft.isbn=&rft.btitle=&rft.title=British+journal+of+cancer&rft.issn=00070920&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-05 N1 - Date created - 1999-03-05 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Int J Cancer. 1989 Mar 15;43(3):415-21 [2925272] Br J Cancer. 1993 May;67(5):877-84 [8494719] Cancer Causes Control. 1993 Jul;4(4):375-82 [8347787] Lancet. 1993 Nov 20;342(8882):1262-5 [7901583] Eur J Cancer. 1994;30A(3):344-50 [8204357] Cancer. 1987 Jun 15;59(12):2112-6 [3567872] Dig Dis Sci. 1996 Feb;41(2):387-91 [8601387] J Gastroenterol. 1996 Aug;31(4):538-45 [8844475] J Surg Res. 1984 Aug;37(2):108-11 [6748630] Cancer Res. 1986 Sep;46(9):4782-6 [3731125] Jpn J Cancer Res. 1986 Jun;77(6):579-83 [3089992] Cancer Causes Control. 1994 May;5(3):267-72 [8061176] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Cholera toxin suppresses interleukin (IL)-12 production and IL-12 receptor beta1 and beta2 chain expression. AN - 69575277; 9927516 AB - Cholera toxin (CT) is a potent mucosal vaccine adjuvant, which has been shown to induce T helper cell type 2 (Th2) responses in systemic and mucosal tissues. We report that CT inhibits the production of interleukin (IL)-12, a major Th2 counterregulatory cytokine. IL-12 p70 production by stimulated human monocytes was inhibited by CT in a dose-dependent manner. This suppression occurred at the level of gene transcription, was maximal at low concentrations of CT, and was dependent on the A subunit of the toxin, since purified CT B subunit had minimal effect. CT also inhibited the production of IL-12 p70 by monocyte-derived dendritic cells, as well as the production of tumor necrosis factor alpha, but not IL-10, IL-6, or transforming growth factor (TGF)-beta1, by stimulated monocytes. The effects of CT were not due to autocrine production of IL-10, TGF-beta1, or prostaglandin E2. CT inhibited the production of IFN-gamma by anti-CD3-stimulated human peripheral blood mononuclear cell, due in part to suppression of IL-12 production, but also to the inhibition of expression of the beta1 and beta2 chains of the IL-12 receptor on T cells. In vivo, mice given CT before systemic challenge with lipopolysaccharide had markedly reduced serum levels of IL-12 p40 and interferon gamma. These data demonstrate two novel mechanisms by which CT can inhibit Th1 immune responses, and help explain the ability of mucosally administered CT to enhance Th2-dependent immune responses. JF - The Journal of experimental medicine AU - Braun, M C AU - He, J AU - Wu, C Y AU - Kelsall, B L AD - Immune Cell Interaction Unit, Mucosal Immunity Section, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 541 EP - 552 VL - 189 IS - 3 SN - 0022-1007, 0022-1007 KW - Adjuvants, Immunologic KW - 0 KW - Antigens, CD3 KW - IL12RB1 protein, human KW - IL12RB2 protein, human KW - Il12rb1 protein, mouse KW - Il12rb2 protein, mouse KW - Lipopolysaccharides KW - RNA, Messenger KW - Receptors, Interleukin KW - Receptors, Interleukin-12 KW - Tumor Necrosis Factor-alpha KW - Interleukin-12 KW - 187348-17-0 KW - Interferon-gamma KW - 82115-62-6 KW - Cholera Toxin KW - 9012-63-9 KW - Index Medicus KW - AIDS/HIV KW - Th1 Cells -- immunology KW - Animals KW - Dose-Response Relationship, Drug KW - Humans KW - Interferon-gamma -- biosynthesis KW - Tumor Necrosis Factor-alpha -- biosynthesis KW - Mice KW - Mucous Membrane -- immunology KW - Antigens, CD3 -- immunology KW - Lipopolysaccharides -- immunology KW - Gene Expression Regulation KW - Th2 Cells -- immunology KW - RNA, Messenger -- isolation & purification KW - Dendritic Cells -- immunology KW - Cholera Toxin -- immunology KW - Interleukin-12 -- biosynthesis KW - Monocytes -- immunology KW - Dendritic Cells -- drug effects KW - Cholera Toxin -- pharmacology KW - Monocytes -- drug effects KW - Interleukin-12 -- genetics KW - Receptors, Interleukin -- biosynthesis UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69575277?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+experimental+medicine&rft.atitle=Cholera+toxin+suppresses+interleukin+%28IL%29-12+production+and+IL-12+receptor+beta1+and+beta2+chain+expression.&rft.au=Braun%2C+M+C%3BHe%2C+J%3BWu%2C+C+Y%3BKelsall%2C+B+L&rft.aulast=Braun&rft.aufirst=M&rft.date=1999-02-01&rft.volume=189&rft.issue=3&rft.spage=541&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+experimental+medicine&rft.issn=00221007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-02 N1 - Date created - 1999-06-02 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Gastroenterology. 1985 Jul;89(1):27-35 [3891496] Proc Natl Acad Sci U S A. 1986 Aug;83(15):5673-7 [3016713] Biochem J. 1986 Sep 1;238(2):313-22 [3541910] J Immunol. 1987 Dec 1;139(11):3764-70 [2824614] J Immunol. 1989 Jan 1;142(1):20-7 [2783324] Immunology. 1989 Mar;66(3):410-5 [2703255] Immunology. 1989 Mar;66(3):416-21 [2522908] J Immunol. 1989 Jun 1;142(11):3781-7 [2785565] J Exp Med. 1989 Sep 1;170(3):1039-44 [2788703] J Immunol. 1989 Dec 1;143(11):3647-52 [2555413] J Exp Med. 1990 Jul 1;172(1):95-103 [2162906] J Immunol. 1991 May 1;146(9):2908-14 [1901890] Scand J Immunol. 1991 Jun;33(6):691-8 [1710819] Microbiol Rev. 1992 Dec;56(4):622-47 [1480112] J Immunol. 1993 Apr 15;150(8 Pt 1):3274-83 [8468469] Scand J Immunol. 1993 Apr;37(4):452-8 [8469928] Eur J Immunol. 1993 Sep;23(9):2136-43 [8370397] J Exp Med. 1993 Oct 1;178(4):1309-20 [8376936] J Immunol. 1994 May 1;152(9):4663-70 [8157979] Immunology. 1994 Mar;81(3):338-42 [8206507] J Immunol. 1994 Jul 15;153(2):647-57 [8021502] J Clin Invest. 1997 Sep 15;100(6):1513-9 [9294119] Nature. 1997 Oct 16;389(6652):737-42 [9338786] Infect Immun. 1997 Nov;65(11):4734-7 [9353058] J Immunol. 1997 Nov 15;159(10):5157-61 [9366446] Immunology. 1997 Sep;92(1):60-8 [9370925] Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1709-14 [9465081] J Clin Immunol. 1998 Jan;18(1):1-30 [9475350] Immunol Res. 1998;17(1-2):269-78 [9479588] J Immunol. 1998 Mar 1;160(5):2174-9 [9498755] Int Rev Immunol. 1998;16(3-4):365-96 [9505196] Nature. 1998 Mar 19;392(6673):245-52 [9521319] J Immunol. 1997 Dec 1;159(11):5301-8 [9548469] J Immunol. 1998 Feb 1;160(3):1132-8 [9570526] J Immunol. 1998 Feb 1;160(3):1198-203 [9570534] Res Immunol. 1997 Oct-Dec;148(8-9):504-20 [9588829] Scand J Immunol. 1998 May;47(5):401-7 [9627122] Infect Immun. 1998 Jul;66(7):3480-4 [9632629] J Immunol. 1998 Jun 15;160(12):5719-28 [9637480] J Immunol. 1998 Jun 15;160(12):5936-44 [9637507] J Exp Med. 1998 Jul 6;188(1):217-22 [9653099] J Immunol. 1998 Dec 15;161(12):6567-74 [9862683] J Immunol. 1996 Nov 15;157(10):4521-8 [8906830] Cell Immunol. 1996 Sep 15;172(2):224-8 [8964084] Ann N Y Acad Sci. 1996 Oct 31;795:60-70 [8958917] J Immunol. 1997 Jan 15;158(2):834-41 [8993001] J Exp Med. 1997 Feb 3;185(3):415-27 [9053442] J Immunol. 1997 May 1;158(9):4381-8 [9127002] Proc Natl Acad Sci U S A. 1997 May 13;94(10):5267-72 [9144226] J Exp Med. 1997 Jun 2;185(11):1977-85 [9166427] J Exp Med. 1997 Jun 2;185(11):1987-95 [9166428] Eur J Immunol. 1997 May;27(5):1213-20 [9174613] Immunol Rev. 1997 Apr;156:25-37 [9176697] Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6688-92 [8022835] Infect Immun. 1994 Oct;62(10):4244-9 [7927680] Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10795-9 [7526379] Blood. 1994 Dec 15;84(12):4008-27 [7994020] J Exp Med. 1995 Jan 1;181(1):41-53 [7807021] Int Immunol. 1994 Sep;6(9):1333-43 [7819141] J Immunol. 1995 Feb 1;154(3):1032-40 [7822780] J Exp Med. 1995 Feb 1;181(2):775-9 [7836930] Vaccine. 1994 Oct;12(13):1238-40 [7839730] Eur J Immunol. 1995 Mar;25(3):672-6 [7705395] Infect Immun. 1995 Jun;63(6):2100-8 [7768587] Immunity. 1995 Jun;2(6):665-75 [7796298] J Exp Med. 1995 Nov 1;182(5):1281-90 [7595199] J Immunol. 1995 Nov 15;155(10):4621-9 [7594461] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):388-91 [8552644] J Exp Med. 1996 Jan 1;183(1):147-57 [8551218] J Infect Dis. 1996 Mar;173(3):627-35 [8627026] Infect Immun. 1996 May;64(5):1516-25 [8613355] Immunity. 1996 May;4(5):471-81 [8630732] J Exp Med. 1996 Mar 1;183(3):901-13 [8642294] J Immunol. 1996 Jun 1;156(11):4137-45 [8666780] Science. 1996 Jul 12;273(5272):228-31 [8662504] J Exp Med. 1996 Aug 1;184(2):473-83 [8760801] J Immunol. 1996 Sep 15;157(6):2348-57 [8805632] Crit Rev Immunol. 1995;15(3-4):317-48 [8834454] J Immunol Methods. 1996 Sep 27;196(2):121-35 [8841451] Immunology. 1997 Jun;91(2):197-203 [9227317] Immunol Today. 1997 Jul;18(7):335-43 [9238837] J Immunol. 1997 Aug 15;159(4):1658-65 [9257825] J Immunol. 1975 Feb;114(2 pt 2):863-71 [1112982] Infect Immun. 1982 Nov;38(2):424-33 [7141703] J Immunol. 1984 Dec;133(6):2892-7 [6491278] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. AN - 69573492; 9989566 AB - Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents. After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents. Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone. The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed. JF - The American journal of psychiatry AU - Breier, A F AU - Malhotra, A K AU - Su, T P AU - Pinals, D A AU - Elman, I AU - Adler, C M AU - Lafargue, R T AU - Clifton, A AU - Pickar, D AD - Experimental Therapeutics Branch, Division of Intramural Research Programs, NIMH, Bethesda, MD, USA. breiervalan@lily.com Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 294 EP - 298 VL - 156 IS - 2 SN - 0002-953X, 0002-953X KW - Antipsychotic Agents KW - 0 KW - Human Growth Hormone KW - 12629-01-5 KW - Prolactin KW - 9002-62-4 KW - Clozapine KW - J60AR2IKIC KW - Risperidone KW - L6UH7ZF8HC KW - Hydrocortisone KW - WI4X0X7BPJ KW - Abridged Index Medicus KW - Index Medicus KW - Drug Administration Schedule KW - Double-Blind Method KW - Humans KW - Adult KW - Treatment Outcome KW - Schizophrenic Psychology KW - Chronic Disease KW - Human Growth Hormone -- blood KW - Psychiatric Status Rating Scales -- statistics & numerical data KW - Male KW - Hydrocortisone -- blood KW - Female KW - Basal Ganglia Diseases -- epidemiology KW - Basal Ganglia Diseases -- chemically induced KW - Schizophrenia -- blood KW - Parkinson Disease, Secondary -- chemically induced KW - Prolactin -- blood KW - Clozapine -- therapeutic use KW - Antipsychotic Agents -- therapeutic use KW - Schizophrenia -- diagnosis KW - Schizophrenia -- drug therapy KW - Risperidone -- adverse effects KW - Clozapine -- adverse effects KW - Antipsychotic Agents -- adverse effects KW - Risperidone -- therapeutic use UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69573492?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+American+journal+of+psychiatry&rft.atitle=Clozapine+and+risperidone+in+chronic+schizophrenia%3A+effects+on+symptoms%2C+parkinsonian+side+effects%2C+and+neuroendocrine+response.&rft.au=Breier%2C+A+F%3BMalhotra%2C+A+K%3BSu%2C+T+P%3BPinals%2C+D+A%3BElman%2C+I%3BAdler%2C+C+M%3BLafargue%2C+R+T%3BClifton%2C+A%3BPickar%2C+D&rft.aulast=Breier&rft.aufirst=A&rft.date=1999-02-01&rft.volume=156&rft.issue=2&rft.spage=294&rft.isbn=&rft.btitle=&rft.title=The+American+journal+of+psychiatry&rft.issn=0002953X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment In: Am J Psychiatry. 2000 Feb;157(2):310 [10671435] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - N-(2-chloroethyl)-N-nitrosourea tethered to lexitropsin induces minor groove lesions at the p53 cDNA that are more cytotoxic than mutagenic. AN - 69569797; 9973219 AB - Many different N-chloroethyl-N-nitrosourea (CENU) derivatives have been synthesized in an attempt to minimize carcinogenic activity while favoring antineoplastic activity. CENU derivatives linked to the dipeptide lexitropsin (lex) showed significant changes in groove- and sequence-selective DNA alkylation inducing thermolabile N3-alkyladenines (N3-Alkyl-As) at lex equilibrium binding sites. CENU-lex sequence specificity for DNA alkylation was determined using 32P-end-labeled restriction fragments of the p53 cDNA. The adducted sites were converted into single-strand breaks by sequential heating at neutral pH and exposure to piperidine. To establish the mutagenic and lethal properties of CENU-lex-specific lesions, a yeast expression vector harboring a human wild-type p53 cDNA was treated in vitro with CENU-lex and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. p53 mutants were isolated from independent ade- transformants. The results revealed that: (a) CENU-lex preferentially induces N3-Alkyl-A at specific lex equilibrium binding sites, the formations of which are strongly inhibited by distamycin; (b) reactivity toward Gs is still present, albeit to a lesser extent when compared to N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea and to CENU; (c) 91% of the 49 CENU-lex p53 mutations (45 of 49) were bp substitutions, 29 of which were GC-->AT transitions, mainly at 5' purine G sites; (d) all AT-targeted mutations but one were AT-->TA transversions; (e) the distribution of the CENU-lex mutations along the p53 cDNA was not random, with position 273 (codon 91), where only GC-->AT transitions were observed, being a real (n = 3, P < 0.0002) CENU-lex mutation hot spot; and (f) a shift in DNA alkylation sites between lesion spectra induced by CENU-lex and N-(2-chloroethyl-N-cyclohexyl-N-nitrosourea was associated with an increased lethality and a decreased mutagenicity, whereas no dramatic change in mutational specificity was observed. Hence, it is tempting to conclude that, in this experimental system, N3-Alkyl-A is more lethal than mutagenic, whereas O6-alkylguanine is a common premutational lesion formed at non-lex binding sites. These results suggest that CENU derivatives with virtually absolute specificity for A residues would make targeting of lethal, nonmutagenic lesions at A+T-rich regions possible, and this may represent a new strategy for the development of new chemotherapeutic agents with a higher therapeutic index. JF - Cancer research AU - Inga, A AU - Chen, F X AU - Monti, P AU - Aprile, A AU - Campomenosi, P AU - Menichini, P AU - Ottaggio, L AU - Viaggi, S AU - Abbondandolo, A AU - Gold, B AU - Fronza, G AD - CSTA-Mutagenesis Laboratory, National Cancer Institute (IST), Genova, Italy. Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 689 EP - 695 VL - 59 IS - 3 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - DNA, Complementary KW - Mutagens KW - lexitropsin KW - 110124-49-7 KW - 1-(2-chloroethyl)-1-nitrosourea KW - 2365-30-2 KW - Netropsin KW - 64B3O0RD7N KW - Ethylnitrosourea KW - P8M1T4190R KW - Index Medicus KW - Base Sequence KW - Transfection KW - Humans KW - Molecular Sequence Data KW - Structure-Activity Relationship KW - Alkylation KW - Netropsin -- chemistry KW - DNA, Complementary -- genetics KW - Genes, p53 -- drug effects KW - Ethylnitrosourea -- analogs & derivatives KW - Mutagens -- toxicity KW - Mutagens -- pharmacology KW - Netropsin -- toxicity KW - Netropsin -- pharmacology KW - DNA, Complementary -- drug effects KW - Ethylnitrosourea -- chemistry KW - Ethylnitrosourea -- toxicity KW - DNA, Complementary -- metabolism KW - Antineoplastic Agents -- toxicity KW - Antineoplastic Agents -- pharmacology KW - Netropsin -- analogs & derivatives KW - Ethylnitrosourea -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69569797?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=N-%282-chloroethyl%29-N-nitrosourea+tethered+to+lexitropsin+induces+minor+groove+lesions+at+the+p53+cDNA+that+are+more+cytotoxic+than+mutagenic.&rft.au=Inga%2C+A%3BChen%2C+F+X%3BMonti%2C+P%3BAprile%2C+A%3BCampomenosi%2C+P%3BMenichini%2C+P%3BOttaggio%2C+L%3BViaggi%2C+S%3BAbbondandolo%2C+A%3BGold%2C+B%3BFronza%2C+G&rft.aulast=Inga&rft.aufirst=A&rft.date=1999-02-01&rft.volume=59&rft.issue=3&rft.spage=689&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - A pilot study: use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures. AN - 69569681; 9972969 AB - To study the effects of the adenine analog, fludarabine, on patients with refractory dermatomyositis and polymyositis, and to assess variables used in following myositis patients during medical intervention. Patients whose myositis was not controlled by prednisone and at least one other immunosuppressive medication were entered into a pilot study during which they received 6 monthly cycles of intravenous fludarabine. Patients were assessed at baseline, every other month, and at month 7 for primary outcome measures of strength and function. Other measurements including peripheral blood cell subsets, muscle enzymes, and various assessments of disease activity were followed monthly during the fludarabine infusion period and for up to 6 months post therapy. Of 16 patients who entered the study, 4 patients were classified as improved, and 7 patients were classified as unchanged. Five patients who withdrew before month 7 were classified as treatment failures. Fludarabine caused a significant and prolonged lymphopenia without an increase in infectious complications over that seen with other immunosuppressive agents used for myositis. A sudden death of one patient at the end of the study was not thought to be drug related. Variables followed during the study emphasized the distinction between patient functional improvement and disease remission. A subset of patients with refractory myositis may benefit from fludarabine therapy and controlled trials are indicated. Refinement and validation of variables useful for following myositis patients await larger studies. JF - The Journal of rheumatology AU - Adams, E M AU - Pucino, F AU - Yarboro, C AU - Hicks, J E AU - Thornton, B AU - McGarvey, C AU - Sonies, B C AU - Bartlett, M L AU - Villalba, M L AU - Fleisher, T AU - Plotz, P H AD - Arthritis Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 352 EP - 360 VL - 26 IS - 2 SN - 0315-162X, 0315-162X KW - Anti-Inflammatory Agents KW - 0 KW - Immunosuppressive Agents KW - Vidarabine KW - FA2DM6879K KW - fludarabine KW - P2K93U8740 KW - Prednisone KW - VB0R961HZT KW - Index Medicus KW - Magnetic Resonance Imaging KW - Muscle, Skeletal -- pathology KW - Prednisone -- therapeutic use KW - Humans KW - Anti-Inflammatory Agents -- therapeutic use KW - Edema -- pathology KW - Aged KW - Pilot Projects KW - Edema -- drug therapy KW - Hematologic Tests KW - Adult KW - Treatment Outcome KW - Flow Cytometry KW - Middle Aged KW - Female KW - Male KW - Dermatomyositis -- drug therapy KW - Vidarabine -- analogs & derivatives KW - Polymyositis -- drug therapy KW - Vidarabine -- therapeutic use KW - Vidarabine -- adverse effects KW - Immunosuppressive Agents -- therapeutic use KW - Immunosuppressive Agents -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69569681?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+rheumatology&rft.atitle=A+pilot+study%3A+use+of+fludarabine+for+refractory+dermatomyositis+and+polymyositis%2C+and+examination+of+endpoint+measures.&rft.au=Adams%2C+E+M%3BPucino%2C+F%3BYarboro%2C+C%3BHicks%2C+J+E%3BThornton%2C+B%3BMcGarvey%2C+C%3BSonies%2C+B+C%3BBartlett%2C+M+L%3BVillalba%2C+M+L%3BFleisher%2C+T%3BPlotz%2C+P+H&rft.aulast=Adams&rft.aufirst=E&rft.date=1999-02-01&rft.volume=26&rft.issue=2&rft.spage=352&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+rheumatology&rft.issn=0315162X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-30 N1 - Date created - 1999-06-30 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Pre- versus postinjury effects of intravenous GABAergic anesthetics on formalin-induced Fos immunoreactivity in the rat spinal cord. AN - 69568432; 9972767 AB - We evaluated the suppression of spinal Fos-like immunoreactivity (FLI) by i.v. anesthetics in the rat formalin model. Preformalin injection (1.5% subcutaneously) treatment groups included i.v. saline controls and three i.v. GABAergic anesthetic groups (pentobarbital 20 mg/kg, propofol 10 mg/kg, or alphaxalone 1.5 mg/kg; n = 12 per group). After perfusion 2 h postformalin, spinal cords were dissected, sliced at 30 microm, and processed by immunoperoxidase staining with an antibody against the Fos protein. Quantification and determination of the laminar distribution of Fos-labeled nuclei were performed at the L4-5 spinal level ipsilateral to formalin injection. Drug groups demonstrating FLI suppression were comparatively studied in a 5-min postformalin treatment group. Pentobarbital pretreatment failed to suppress FLI. However, significant reductions (percent decrease) of FLI were observed with propofol (63%) and alphaxalone (30%) compared with saline controls. Pre- versus postformalin comparison studies showed that propofol, but not alphaxalone, suppressed FLI more effectively when given preformalin. Given the observed inconsistencies between this study of Fos expression and our previous behavioral study, it is questionable whether anesthetic modulation of noxious stimulus-induced FLI parallels that of behavioral responses. In this study, we examined whether i.v. general anesthetics (propofol, alphaxalone, and pentobarbital) prevent injury-induced spinal cord changes. We measured spinal Fos protein after rats received anesthetics before versus after a formalin injection. Fos inhibition patterns were inconsistent with behavioral studies of these anesthetics, suggesting that Fos inhibition does not always correlate with behavioral analgesia. JF - Anesthesia and analgesia AU - Gilron, I AU - Quirion, R AU - Coderre, T J AD - National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. igilron@yoda.nidr.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 414 EP - 420 VL - 88 IS - 2 SN - 0003-2999, 0003-2999 KW - Adjuvants, Anesthesia KW - 0 KW - Analgesics KW - Anesthetics KW - Anesthetics, Intravenous KW - Coloring Agents KW - Fixatives KW - GABA Modulators KW - Pregnanediones KW - Proto-Oncogene Proteins c-fos KW - Formaldehyde KW - 1HG84L3525 KW - alphaxalone KW - BD07M97B2A KW - Pentobarbital KW - I4744080IR KW - Propofol KW - YI7VU623SF KW - Abridged Index Medicus KW - Index Medicus KW - Propofol -- pharmacology KW - Animals KW - Analysis of Variance KW - Rats, Long-Evans KW - Anesthetics -- pharmacology KW - Cell Nucleus -- immunology KW - Disease Models, Animal KW - Cell Nucleus -- drug effects KW - Cytoplasm -- drug effects KW - Pentobarbital -- pharmacology KW - Rats KW - Adjuvants, Anesthesia -- pharmacology KW - Cytoplasm -- immunology KW - Injections, Subcutaneous KW - Pregnanediones -- pharmacology KW - Male KW - Immunoenzyme Techniques KW - Lumbar Vertebrae KW - Proto-Oncogene Proteins c-fos -- drug effects KW - Spinal Cord -- immunology KW - GABA Modulators -- pharmacology KW - Anesthetics, Intravenous -- pharmacology KW - Spinal Cord -- drug effects KW - Proto-Oncogene Proteins c-fos -- immunology KW - Formaldehyde -- administration & dosage KW - Analgesics -- pharmacology KW - Formaldehyde -- adverse effects KW - Fixatives -- adverse effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69568432?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesia+and+analgesia&rft.atitle=Pre-+versus+postinjury+effects+of+intravenous+GABAergic+anesthetics+on+formalin-induced+Fos+immunoreactivity+in+the+rat+spinal+cord.&rft.au=Gilron%2C+I%3BQuirion%2C+R%3BCoderre%2C+T+J&rft.aulast=Gilron&rft.aufirst=I&rft.date=1999-02-01&rft.volume=88&rft.issue=2&rft.spage=414&rft.isbn=&rft.btitle=&rft.title=Anesthesia+and+analgesia&rft.issn=00032999&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Upregulated expression of fibronectin receptors underlines the adhesive capability of thymocytes to thymic epithelial cells during the early stages of differentiation: lessons from sublethally irradiated mice. AN - 69564245; 9920847 AB - A 250-cGy whole-body gamma-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3(-)CD25(hi)CD44(+) and CD3(-)CD25(in/hi)CD44(-) cells occurred. Enhanced expression of L-selectin, alpha4, and alpha5 integrin chains (L-selhi alpha4(hi) alpha5(hi)) was also exhibited by these cells. This pattern of expression was maintained until the CD4(+)CD8(+) (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4(+) or CD8(+) single positive (SP) thymocytes (L-selin alpha4(in) alpha5(in)). In some recently generated SP cells, alpha4 expression was downregulated before the alpha5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the alpha6 integrin chain was downregulated only in maturing CD4(+) cells. Importantly, the increased expression of L-selectin and alpha4 and alpha5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the alpha4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for alpha5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the beta1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25(+) precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components. JF - Blood AU - Dalmau, S R AU - Freitas, C S AU - Savino, W AD - Program of Experimental Medicine, Basic Research Center, National Cancer Institute, Rio de Janeiro, Brazil. Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 974 EP - 990 VL - 93 IS - 3 SN - 0006-4971, 0006-4971 KW - Antibodies, Monoclonal KW - 0 KW - Antigens, CD KW - Integrin alpha5 KW - Integrin alpha6 KW - Oligopeptides KW - Peptide Fragments KW - Receptors, Fibronectin KW - Receptors, Interleukin-2 KW - tyrosyl-isoleucyl-glycyl-seryl-arginine KW - 110590-64-2 KW - L-Selectin KW - 126880-86-2 KW - Integrin alpha4 KW - 143198-26-9 KW - arginyl-glycyl-aspartic acid KW - 78VO7F77PN KW - glycyl-arginyl-glycyl-aspartyl-serine KW - 96426-21-0 KW - Protein-Tyrosine Kinases KW - EC 2.7.10.1 KW - Abridged Index Medicus KW - Index Medicus KW - Space life sciences KW - Antigens, CD -- biosynthesis KW - Radiation Injuries, Experimental -- pathology KW - Animals KW - Extracellular Matrix -- metabolism KW - Receptors, Interleukin-2 -- analysis KW - Antigens, CD -- genetics KW - Immunologic Deficiency Syndromes -- pathology KW - Phosphorylation KW - Male KW - Peptide Fragments -- metabolism KW - Epithelial Cells -- physiology KW - Antibodies, Monoclonal -- metabolism KW - Protein Processing, Post-Translational KW - Cell Differentiation KW - Mice KW - Protein-Tyrosine Kinases -- metabolism KW - Radiation Injuries, Experimental -- immunology KW - L-Selectin -- genetics KW - Regeneration KW - L-Selectin -- biosynthesis KW - Mice, Inbred C57BL KW - Oligopeptides -- metabolism KW - Immunologic Deficiency Syndromes -- etiology KW - Female KW - Cell Adhesion KW - Thymus Gland -- cytology KW - T-Lymphocyte Subsets -- physiology KW - Thymus Gland -- radiation effects KW - Receptors, Fibronectin -- biosynthesis KW - Thymus Gland -- embryology KW - Up-Regulation KW - Thymus Gland -- physiology KW - Receptors, Fibronectin -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69564245?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Upregulated+expression+of+fibronectin+receptors+underlines+the+adhesive+capability+of+thymocytes+to+thymic+epithelial+cells+during+the+early+stages+of+differentiation%3A+lessons+from+sublethally+irradiated+mice.&rft.au=Dalmau%2C+S+R%3BFreitas%2C+C+S%3BSavino%2C+W&rft.aulast=Dalmau&rft.aufirst=S&rft.date=1999-02-01&rft.volume=93&rft.issue=3&rft.spage=974&rft.isbn=&rft.btitle=&rft.title=Blood&rft.issn=00064971&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. AN - 69563494; 9973225 AB - Expression and function of the TRAIL apoptotic pathway was investigated in normal and malignant breast epithelial cells. Glutathione-S-transferase (GST)-TRAIL extracellular domain fusion proteins were produced to analyze TRAIL-induced apoptosis. Only GST-TRAIL constructs containing regions homologous to the Fas self-association and ligand binding domains could induce apoptosis. GST-TRAIL induced significant (>90%) apoptosis in just one of eight normal and one of eight malignant breast cell lines. All other lines were relatively resistant to TRAIL-induced apoptosis. Activating TRAIL receptors DR4 and DR5 were expressed in all normal and malignant breast cell lines. The inhibitory receptor TRID was highly expressed in one of four normal and two of seven malignant breast cell lines. DR4, DR5, or TRID expression did not correlate with sensitivity to TRAIL-induced apoptosis. Incubation of cell lines with doxorubicin or 5-fluorouracil significantly augmented TRAIL-induced apoptosis in most breast cell lines. By fractional inhibition analysis, the toxicity of the combination of TRAIL and doxorubicin or 5-fluorouracil was synergistic compared with either agent alone. In contrast, melphalan and paclitaxel augmented TRAIL-induced apoptosis in few cell lines, and methotrexate did not augment it in any cell line. Augmentation of TRAIL-induced apoptosis by doxorubicin or 5-fluorouracil was mediated through caspase activation. This was evidenced by the fact that chemotherapy agents that synergized with TRAIL (e.g., doxorubicin) themselves caused cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP), and their toxicity was blocked by the caspase inhibitor Z-Val-Ala-Asp(OMe)-CH2 (ZVAD-fmk). The combination of TRAIL and doxorubicin caused significantly greater caspase-3 and PARP cleavage, and the combined toxicity also was inhibited by ZVAD-fmk. In contrast, chemotherapy agents that did not augment TRAIL-induced apoptosis (e.g., methotrexate) caused minimal caspase-3 and PARP cleavage by themselves, and their toxicity was not inhibited by ZVAD-fmk. These drugs also did not increase caspase-3 or PARP cleavage when combined with TRAIL. In summary, few breast cell lines are sensitive to TRAIL-induced apoptosis, and no difference in sensitivity is found between normal and malignant cell lines. Treatment with chemotherapy provides an approach to sensitize breast cancer cells to TRAIL-induced apoptosis. JF - Cancer research AU - Keane, M M AU - Ettenberg, S A AU - Nau, M M AU - Russell, E K AU - Lipkowitz, S AD - National Cancer Institute, Division of Clinical Sciences, Medicine Branch, National Naval Medical Center, Bethesda, Maryland 20889-5105, USA. Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 734 EP - 741 VL - 59 IS - 3 SN - 0008-5472, 0008-5472 KW - Antineoplastic Agents KW - 0 KW - Apoptosis Regulatory Proteins KW - Membrane Glycoproteins KW - Recombinant Fusion Proteins KW - TNF-Related Apoptosis-Inducing Ligand KW - TNFSF10 protein, human KW - Tumor Necrosis Factor-alpha KW - Doxorubicin KW - 80168379AG KW - Glutathione Transferase KW - EC 2.5.1.18 KW - CASP3 protein, human KW - EC 3.4.22.- KW - Caspase 3 KW - Caspases KW - Paclitaxel KW - P88XT4IS4D KW - Melphalan KW - Q41OR9510P KW - Fluorouracil KW - U3P01618RT KW - Index Medicus KW - Paclitaxel -- administration & dosage KW - Antineoplastic Agents -- administration & dosage KW - Enzyme Activation KW - Glutathione Transferase -- pharmacology KW - Humans KW - Paclitaxel -- pharmacology KW - Doxorubicin -- administration & dosage KW - Melphalan -- pharmacology KW - Caspases -- metabolism KW - Fluorouracil -- administration & dosage KW - Glutathione Transferase -- physiology KW - Tumor Cells, Cultured KW - Doxorubicin -- pharmacology KW - Melphalan -- administration & dosage KW - Recombinant Fusion Proteins -- pharmacology KW - Fluorouracil -- pharmacology KW - Breast Neoplasms -- drug therapy KW - Tumor Necrosis Factor-alpha -- administration & dosage KW - Membrane Glycoproteins -- physiology KW - Breast Neoplasms -- pathology KW - Apoptosis -- physiology KW - Tumor Necrosis Factor-alpha -- pharmacology KW - Apoptosis -- drug effects KW - Tumor Necrosis Factor-alpha -- physiology KW - Antineoplastic Combined Chemotherapy Protocols -- pharmacology KW - Membrane Glycoproteins -- pharmacology KW - Membrane Glycoproteins -- administration & dosage UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563494?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+research&rft.atitle=Chemotherapy+augments+TRAIL-induced+apoptosis+in+breast+cell+lines.&rft.au=Keane%2C+M+M%3BEttenberg%2C+S+A%3BNau%2C+M+M%3BRussell%2C+E+K%3BLipkowitz%2C+S&rft.aulast=Keane&rft.aufirst=M&rft.date=1999-02-01&rft.volume=59&rft.issue=3&rft.spage=734&rft.isbn=&rft.btitle=&rft.title=Cancer+research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Radiation-induced progressive decrease in fluid secretion in rat submandibular glands is related to decreased acinar volume and not impaired calcium signaling. AN - 69563052; 9952299 AB - The mechanism(s) of radiation-induced salivary gland dysfunction is poorly understood. In the present study, we have assessed the secretory function (muscarinic agonist-stimulated saliva flow, intracellular calcium mobilization, Na+/K+/2Cl- cotransport activity) in rat submandibular glands 12 months postirradiation (single dose, 10 Gy). The morphological status of glands from control and irradiated rats was also determined. Pilocarpine-stimulated salivary flow was decreased by 67% at 12 months (but not at 3 months) after irradiation. This was associated with a 47% decrease in the wet weight of the irradiated glands. Histological and morphometric analysis demonstrated that acinar cells were smaller and occupied relatively less volume and convoluted granular tubules were smaller but occupied the same relative volume, while intercalated and striated ducts maintained their size but occupied a greater relative volume in submandibular glands from irradiated compared to control animals. In addition, no inflammation or fibrosis was observed in the irradiated tissues. Carbachol- or thapsigargin-stimulated mobilization of Ca2+ was similar in dispersed submandibular gland cells from control and irradiated animals. Further, [Ca2+]i imaging of individual ducts and acini from control and irradiated groups showed, for the first time, that mobilization of Ca2+ in either cell type was not altered by the radiation treatment. The carbachol-stimulated, bumetanide-sensitive component of the Na+/K+/ 2Cl- cotransport activity was also similar in submandibular gland cells from control and irradiated animals. These data demonstrate that a single dose of gamma radiation induces a progressive loss of submandibular gland tissue and function. This loss of salivary flow is not due to chronic inflammation or fibrosis of the gland or an alteration in the neurotransmitter signaling mechanism in the acinar or ductal cells. The radiation-induced decrease in fluid secretion appears to be related to a change in either the water-handling capacity of the acini or the number of acinar cells in the gland. JF - Radiation research AU - O'Connell, A C AU - Redman, R S AU - Evans, R L AU - Ambudkar, I S AD - Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 150 EP - 158 VL - 151 IS - 2 SN - 0033-7587, 0033-7587 KW - Carrier Proteins KW - 0 KW - Muscarinic Agonists KW - Receptors, Muscarinic KW - Sodium-Potassium-Chloride Symporters KW - Carbachol KW - 8Y164V895Y KW - Calcium KW - SY7Q814VUP KW - Index Medicus KW - Space life sciences KW - Submandibular Gland Diseases -- physiopathology KW - Animals KW - Radiation Injuries, Experimental -- metabolism KW - Carrier Proteins -- metabolism KW - Stimulation, Chemical KW - Secretory Rate -- drug effects KW - Rats KW - Receptors, Muscarinic -- radiation effects KW - Saliva -- radiation effects KW - Carrier Proteins -- radiation effects KW - Muscarinic Agonists -- pharmacology KW - Saliva -- secretion KW - Rats, Wistar KW - Submandibular Gland Diseases -- etiology KW - Radiation Injuries, Experimental -- etiology KW - Organ Size -- radiation effects KW - Submandibular Gland Diseases -- metabolism KW - Secretory Rate -- radiation effects KW - Radiation Injuries, Experimental -- physiopathology KW - Receptors, Muscarinic -- physiology KW - Carbachol -- pharmacology KW - Male KW - Signal Transduction -- physiology KW - Submandibular Gland -- anatomy & histology KW - Submandibular Gland -- radiation effects KW - Signal Transduction -- drug effects KW - Calcium -- physiology KW - Signal Transduction -- radiation effects KW - Submandibular Gland -- secretion UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563052?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Radiation+research&rft.atitle=Radiation-induced+progressive+decrease+in+fluid+secretion+in+rat+submandibular+glands+is+related+to+decreased+acinar+volume+and+not+impaired+calcium+signaling.&rft.au=O%27Connell%2C+A+C%3BRedman%2C+R+S%3BEvans%2C+R+L%3BAmbudkar%2C+I+S&rft.aulast=O%27Connell&rft.aufirst=A&rft.date=1999-02-01&rft.volume=151&rft.issue=2&rft.spage=150&rft.isbn=&rft.btitle=&rft.title=Radiation+research&rft.issn=00337587&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-19 N1 - Date created - 1999-02-19 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Immunochemical evidence against the involvement of cysteine conjugate beta-lyase in compound A nephrotoxicity in rats. AN - 69563004; 9952153 AB - Compound A, a degradation product of sevoflurane, causes renal corticomedullary necrosis in rats. Although the toxicity of this compound was originally hypothesized to result from the biotransformation of its cysteine conjugates into toxic thionoacyl halide metabolites by renal cysteine conjugate beta-lyase, recent evidence suggests that alternative mechanisms may be responsible for compound A nephrotoxicity. The aim of this study was to evaluate these issues by determining whether mercapturates and glutathione conjugates of compound A could produce renal corticomedullary necrosis in rats, similar to compound A, and whether renal covalent adducts of the thionacyl halide metabolite of compound A could be detected immunochemically. Male Wistar rats were administered, intraperitoneally, N-acetylcysteine conjugates (mercapturates) of compound A (90 or 180 micromol/kg) or glutathione conjugates of compound A (180 micromol/kg) with or without intraperitoneal pretreatments with aminooxyacetic acid (500 micromol/kg) or acivicin (250 micromol/kg). Rats were killed after 24 h, and kidney tissues were analyzed for toxicity by histologic examination or for protein adducts by immunoblotting or immunohistochemical analysis, using antisera raised against the covalently bound thionoacyl halide metabolite of compound A. Mercapturates and glutathione conjugates of compound A both produced renal corticomedullary necrosis similar to that caused by compound A. Aminooxyacetic acid, an inhibitor of renal cysteine conjugate beta-lyase, did not inhibit the toxicity of the mercapturates, whereas acivicin, an inhibitor of gamma-glutamyltranspeptidase, potentiated the toxicity of both classes of conjugates. No immunochemical evidence for renal protein adducts of the thionacyl halide metabolite was found in rats 24 h after the administration of the mercapturates of compound A or in the kidneys of rats, obtained from a previous study, 5 and 24 h after the administration of compound A. The results of this study are consistent with the idea that a mechanism other than the renal cysteine conjugate beta-lyase pathway of metabolic activation is responsible for the nephrotoxicity of compound A and its glutathione and mercapturate conjugates in male Wistar rats. JF - Anesthesiology AU - Njoku, D B AU - Pohl, L R AU - Sokoloski, E A AU - Marchick, M R AU - Borkowf, C B AU - Martin, J L AD - Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. NjokuD@gwgate.nhlbi.nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 458 EP - 469 VL - 90 IS - 2 SN - 0003-3022, 0003-3022 KW - Anesthetics, Inhalation KW - 0 KW - Ethers KW - Hydrocarbons, Fluorinated KW - Methyl Ethers KW - sevoflurane KW - 38LVP0K73A KW - fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether KW - 58109-34-5 KW - Carbon-Sulfur Lyases KW - EC 4.4.- KW - S-alkylcysteine lyase KW - EC 4.4.1.6 KW - Abridged Index Medicus KW - Index Medicus KW - Rats KW - Methyl Ethers -- metabolism KW - Animals KW - Necrosis KW - Kidney -- pathology KW - Methyl Ethers -- toxicity KW - Rats, Wistar KW - Kidney -- drug effects KW - Methyl Ethers -- chemistry KW - Male KW - Anesthetics, Inhalation -- toxicity KW - Ethers -- chemistry KW - Hydrocarbons, Fluorinated -- chemistry KW - Ethers -- toxicity KW - Anesthetics, Inhalation -- chemistry KW - Carbon-Sulfur Lyases -- toxicity KW - Hydrocarbons, Fluorinated -- toxicity UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563004?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Anesthesiology&rft.atitle=Immunochemical+evidence+against+the+involvement+of+cysteine+conjugate+beta-lyase+in+compound+A+nephrotoxicity+in+rats.&rft.au=Njoku%2C+D+B%3BPohl%2C+L+R%3BSokoloski%2C+E+A%3BMarchick%2C+M+R%3BBorkowf%2C+C+B%3BMartin%2C+J+L&rft.aulast=Njoku&rft.aufirst=D&rft.date=1999-02-01&rft.volume=90&rft.issue=2&rft.spage=458&rft.isbn=&rft.btitle=&rft.title=Anesthesiology&rft.issn=00033022&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-25 N1 - Date created - 1999-02-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Risk of premenopausal breast cancer and patterns of established breast cancer risk factors among teachers and nurses. AN - 69562703; 9894537 AB - Contrasting results have been published regarding the risk of breast cancer among teachers and nurses. Confounding by reproductive factors may explain the increased risk observed among women in these occupations as information on those factors were not available in most studies. We examined the risk of premenopausal breast cancer among teachers and nurses using occupational histories in a case-control study where information on established risk factors was available. Having ever held a teaching job was not related to breast cancer (OR = 0.74, 95% CI = 0.44-1.28) and women who worked for 10 years or less in this occupation had a non-significant deficit of risk (OR = 0.52, 95% CI = 0.27-1.02). No elevation in risk was found in association with having ever been a nurse (OR = 0.85, 95% CI = 0.45-1.61) or with duration of nursing. Although direct comparison of established risk factors among teachers and nurses and other women in the study showed some evidence of differential distribution, especially when comparing teachers to other women, adjustment for reproductive variables and other breast cancer risk factors did not change the results of this study. These findings suggest that teachers and nurses are not at an increased risk of breast cancer. This study also suggests that established risk factors for premenopausal breast cancer may not explain the elevation of risk found in other studies of teachers and nurses. However, this conclusion is limited by the fact that in the present study teachers and nurses had lower than expected breast cancer risk with or without adjustment for established risk factors. Limitations of this study such as low response rates and limited statistical power should be considered in the interpretation of these findings. JF - American journal of industrial medicine AU - Petralia, S A AU - Vena, J E AU - Freudenheim, J L AU - Michalek, A AU - Goldberg, M S AU - Blair, A AU - Brasure, J AU - Graham, S AD - Department of Social and Preventive Medicine, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, USA. spi126@nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 137 EP - 141 VL - 35 IS - 2 SN - 0271-3586, 0271-3586 KW - Index Medicus KW - Parity KW - Odds Ratio KW - Age Factors KW - Educational Status KW - Reproductive History KW - Humans KW - Smoking -- adverse effects KW - Lactation KW - Risk Factors KW - Maternal Age KW - Adult KW - Confounding Factors (Epidemiology) KW - Case-Control Studies KW - Menarche KW - Confidence Intervals KW - Middle Aged KW - Time Factors KW - Female KW - Breast Neoplasms -- genetics KW - Teaching KW - Premenopause KW - Nurses KW - Occupational Diseases -- etiology KW - Breast Neoplasms -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69562703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=American+journal+of+industrial+medicine&rft.atitle=Risk+of+premenopausal+breast+cancer+and+patterns+of+established+breast+cancer+risk+factors+among+teachers+and+nurses.&rft.au=Petralia%2C+S+A%3BVena%2C+J+E%3BFreudenheim%2C+J+L%3BMichalek%2C+A%3BGoldberg%2C+M+S%3BBlair%2C+A%3BBrasure%2C+J%3BGraham%2C+S&rft.aulast=Petralia&rft.aufirst=S&rft.date=1999-02-01&rft.volume=35&rft.issue=2&rft.spage=137&rft.isbn=&rft.btitle=&rft.title=American+journal+of+industrial+medicine&rft.issn=02713586&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Characterization of the dose-response of CYP1B1, CYP1A1, and CYP1A2 in the liver of female Sprague-Dawley rats following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. AN - 69560694; 9931287 AB - One of the current knowledge gaps in the evaluation of risk for human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the relationship between gene expression induced by TCDDmore complex biological responses such as altered growth, differentiation, and neoplasia. This study investigates the dose-dependent expression of CYP1A1, CYP1A2,CYP1B1 in the livers of female Sprague-Dawley rats chronically exposed to TCDD. Animals were treated biweekly for 30 weeks with daily averaged doses of 0 to 125 ng TCDD/kg/day. Immunoblot analysis showed that protein levels for CYP1B1, CYP1A1, CYP1A2 exhibited a dose-dependent induction by TCDD. However, CYP1A1 and CYP1A2 protein levels were approximately 100-fold higher than CYP1B1, which could not be detected by either immunoblot analysis or immunohistochemistry in the livers of rats treated with TCDD for 30 weeks at a dose-equivalent less than 35.7 ng/kg/day. In control animals, CYP1A1CYP1A2 RNA levels, measured by quantitative RT-PCR, were 1100-15,000-fold higher than that of CYP1B1, respectively. TCDD induced CYP1B1 RNA levels at all doses, although absolute TCDD-induced levels of CYP1A1CYP1A2 at the highest dose (125 ng/kg/day) were more than 40-fold higher than that of CYP1B1. While the liver concentration of TCDD required for half-maximal induction of CYP1A1, CYP1A2,CYP1B1 RNA levels was similar, the shaping parameter (Hill coefficient) of the dose-response curve for CYP1B1 was significantly higher than that for CYP1A1 or CYP1A2. The low level of TCDD-induced CYP1B1 expression in the liver relative to that of the CYP1A1CYP1A2 suggest that, if CYP1B1 is involved in TCDD-induced hepatocarcinogenesis, its endogenous function is likely to be uniquenot overlapping with that of CYP1A1 or CYP1A2. Copyright 1999 Academic Press. JF - Toxicology and applied pharmacology AU - Walker, N J AU - Portier, C J AU - Lax, S F AU - Crofts, F G AU - Li, Y AU - Lucier, G W AU - Sutter, T R AD - National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. walker3@niehs.nih.gov Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 279 EP - 286 VL - 154 IS - 3 SN - 0041-008X, 0041-008X KW - Polychlorinated Dibenzodioxins KW - 0 KW - RNA, Messenger KW - Cytochrome P-450 Enzyme System KW - 9035-51-2 KW - Aryl Hydrocarbon Hydroxylases KW - EC 1.14.14.1 KW - CYP1B1 protein, human KW - Cyp1b1 protein, rat KW - Cytochrome P-450 CYP1A1 KW - Cytochrome P-450 CYP1A2 KW - Cytochrome P-450 CYP1B1 KW - Index Medicus KW - Rats KW - Immunoblotting KW - Animals KW - Rats, Sprague-Dawley KW - Microsomes, Liver -- chemistry KW - Time KW - Enzyme Induction -- drug effects KW - Dose-Response Relationship, Drug KW - Microsomes, Liver -- enzymology KW - RNA, Messenger -- analysis KW - Gene Expression Regulation -- drug effects KW - Reverse Transcriptase Polymerase Chain Reaction KW - Female KW - Liver -- enzymology KW - Cytochrome P-450 CYP1A1 -- genetics KW - Cytochrome P-450 CYP1A2 -- genetics KW - Liver -- drug effects KW - Cytochrome P-450 Enzyme System -- genetics KW - Polychlorinated Dibenzodioxins -- toxicity KW - Cytochrome P-450 CYP1A2 -- metabolism KW - Cytochrome P-450 Enzyme System -- metabolism KW - Cytochrome P-450 CYP1A1 -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69560694?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+applied+pharmacology&rft.atitle=Characterization+of+the+dose-response+of+CYP1B1%2C+CYP1A1%2C+and+CYP1A2+in+the+liver+of+female+Sprague-Dawley+rats+following+chronic+exposure+to+2%2C3%2C7%2C8-tetrachlorodibenzo-p-dioxin.&rft.au=Walker%2C+N+J%3BPortier%2C+C+J%3BLax%2C+S+F%3BCrofts%2C+F+G%3BLi%2C+Y%3BLucier%2C+G+W%3BSutter%2C+T+R&rft.aulast=Walker&rft.aufirst=N&rft.date=1999-02-01&rft.volume=154&rft.issue=3&rft.spage=279&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+applied+pharmacology&rft.issn=0041008X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Effects of phentermine on responding maintained under multiple fixed-ratio schedules of food and cocaine presentation in the rhesus monkey. AN - 69559749; 9918558 AB - Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3-10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10-100 microg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3-3 mg/kg) did not generally increase responding associated with a very low (1 microg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1-3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 microg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse. JF - The Journal of pharmacology and experimental therapeutics AU - Wojnicki, F H AU - Rothman, R B AU - Rice, K C AU - Glowa, J R AD - Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 550 EP - 560 VL - 288 IS - 2 SN - 0022-3565, 0022-3565 KW - Central Nervous System Stimulants KW - 0 KW - Dopamine Uptake Inhibitors KW - Piperazines KW - Street Drugs KW - vanoxerine KW - 90X28IKH43 KW - Phentermine KW - C045TQL4WP KW - Cocaine KW - I5Y540LHVR KW - Index Medicus KW - Animals KW - Drug Interactions KW - Dose-Response Relationship, Drug KW - Cocaine-Related Disorders -- drug therapy KW - Macaca mulatta KW - Piperazines -- pharmacology KW - Male KW - Eating -- drug effects KW - Conditioning, Operant -- drug effects KW - Behavior, Animal -- drug effects KW - Central Nervous System Stimulants -- pharmacology KW - Street Drugs -- pharmacology KW - Phentermine -- pharmacology KW - Cocaine -- pharmacology KW - Dopamine Uptake Inhibitors -- pharmacology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69559749?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Effects+of+phentermine+on+responding+maintained+under+multiple+fixed-ratio+schedules+of+food+and+cocaine+presentation+in+the+rhesus+monkey.&rft.au=Wojnicki%2C+F+H%3BRothman%2C+R+B%3BRice%2C+K+C%3BGlowa%2C+J+R&rft.aulast=Wojnicki&rft.aufirst=F&rft.date=1999-02-01&rft.volume=288&rft.issue=2&rft.spage=550&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-22 N1 - Date created - 1999-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Finasteride, a 5alpha-reductase inhibitor, blocks the anticonvulsant activity of progesterone in mice. AN - 69558293; 9918575 AB - Progesterone is an effective anticonvulsant against pentylenetetrazol (PTZ) seizures. This action is hypothesized to require the metabolic conversion of progesterone to the gamma-aminobutyric acidA receptor potentiating neuroactive steroid allopregnanolone by 5alpha-reductase isoenzymes followed by 3alpha-hydroxy oxidoreduction. We evaluated this possibility using the competitive 5alpha-reductase inhibitor finasteride. Progesterone (50-200 mg/kg, i.p.) protected mice against PTZ-induced seizures in a dose-dependent manner (ED50, 94 mg/kg). Pretreatment with finasteride (50-300 mg/kg, i.p.) produced a dose-dependent (ED50, 146 mg/kg) reversal of the protective effects of progesterone (2 x ED50 dose = 188 mg/kg). In contrast, finasteride (up to 300 mg/kg) failed to affect the anticonvulsant activity of allopregnanolone (10-30 mg/kg, i.p.; ED50, 12 mg/kg). Finasteride (up to 300 mg/kg) did not block the protective effect of high doses of progesterone (250-350 mg/kg) on tonic hindlimb extension in the maximal electroshock seizure test (progesterone ED50, 235 mg/kg). The anticonvulsant activity of progesterone against PTZ-induced seizures can be blocked by 5alpha-reductase inhibition, providing strong evidence that the anticonvulsant effect of the steroid in this model is mediated by its active metabolite allopregnanolone. JF - The Journal of pharmacology and experimental therapeutics AU - Kokate, T G AU - Banks, M K AU - Magee, T AU - Yamaguchi, S AU - Rogawski, M A AD - Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1408, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 679 EP - 684 VL - 288 IS - 2 SN - 0022-3565, 0022-3565 KW - Anticonvulsants KW - 0 KW - Convulsants KW - Enzyme Inhibitors KW - Isoenzymes KW - Progesterone KW - 4G7DS2Q64Y KW - Finasteride KW - 57GNO57U7G KW - Pregnanolone KW - BXO86P3XXW KW - Oxidoreductases KW - EC 1.- KW - Cholestenone 5 alpha-Reductase KW - EC 1.3.1.22 KW - Pentylenetetrazole KW - WM5Z385K7T KW - Index Medicus KW - Seizures -- chemically induced KW - Animals KW - Drug Interactions KW - Seizures -- etiology KW - Pregnanolone -- pharmacology KW - Mice KW - Seizures -- prevention & control KW - Electroshock KW - Male KW - Isoenzymes -- antagonists & inhibitors KW - Anticonvulsants -- pharmacology KW - Progesterone -- pharmacology KW - Enzyme Inhibitors -- pharmacology KW - Finasteride -- pharmacology KW - Oxidoreductases -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69558293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.atitle=Finasteride%2C+a+5alpha-reductase+inhibitor%2C+blocks+the+anticonvulsant+activity+of+progesterone+in+mice.&rft.au=Kokate%2C+T+G%3BBanks%2C+M+K%3BMagee%2C+T%3BYamaguchi%2C+S%3BRogawski%2C+M+A&rft.aulast=Kokate&rft.aufirst=T&rft.date=1999-02-01&rft.volume=288&rft.issue=2&rft.spage=679&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.issn=00223565&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-22 N1 - Date created - 1999-02-22 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Protective function of von Hippel-Lindau protein against impaired protein processing in renal carcinoma cells. AN - 69554958; 9891063 AB - The absence of functional von Hippel-Lindau (VHL) tumor suppressor gene leads to the development of neoplasias characteristic of VHL disease, including renal cell carcinoma (RCC). Here, we compared the sensitivity of RCC cells lacking VHL gene function with that of RCC cells expressing the wild-type VHL gene (wtVHL) after exposure to various stresses. While the response to most treatments was not affected by the VHL gene status, glucose deprivation was found to be much more cytotoxic for RCC cells lacking VHL gene function than for wtVHL-expressing cells. The heightened sensitivity of VHL-deficient cells was not attributed to dissimilar energy requirements or to differences in glucose uptake, but more likely reflects a lesser ability of VHL-deficient cells to handle abnormally processed proteins arising from impaired glycosylation. In support of this hypothesis, other treatments which act through different mechanisms to interfere with protein processing (i.e., tunicamycin, brefeldin A, and azetidine) were also found to be much more toxic for VHL-deficient cells. Furthermore, ubiquitination of cellular proteins was elevated in VHL-deficient cells, particularly after glucose deprivation, supporting a role for the VHL gene in ubiquitin-mediated proteolysis. Accordingly, the rate of elimination of abnormal proteins was lower in cells lacking a functional VHL gene than in wtVHL-expressing cells. Thus, pVHL appears to participate in the elimination of misprocessed proteins, such as those arising in the cell due to the unavailability of glucose or to other stresses. JF - Molecular and cellular biology AU - Gorospe, M AU - Egan, J M AU - Zbar, B AU - Lerman, M AU - Geil, L AU - Kuzmin, I AU - Holbrook, N J AD - Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA. myriam-gorospe@nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 1289 EP - 1300 VL - 19 IS - 2 SN - 0270-7306, 0270-7306 KW - Neoplasm Proteins KW - 0 KW - Proteins KW - RNA, Neoplasm KW - RNA, Ribosomal, 18S KW - Tumor Suppressor Proteins KW - Ubiquitins KW - Ubiquitin-Protein Ligases KW - EC 2.3.2.27 KW - Von Hippel-Lindau Tumor Suppressor Protein KW - Ligases KW - EC 6.- KW - VHL protein, human KW - EC 6.3.2.- KW - Glucose KW - IY9XDZ35W2 KW - Index Medicus KW - Apoptosis KW - Glucose -- metabolism KW - Humans KW - Protein Processing, Post-Translational KW - Glycosylation KW - RNA, Neoplasm -- genetics KW - Energy Metabolism KW - Genes, bcl-2 KW - Base Sequence KW - Ubiquitins -- metabolism KW - Tumor Cells, Cultured KW - Neoplasm Proteins -- genetics KW - RNA, Ribosomal, 18S -- genetics KW - Neoplasm Proteins -- metabolism KW - Kidney Neoplasms -- genetics KW - Carcinoma, Renal Cell -- etiology KW - Carcinoma, Renal Cell -- metabolism KW - von Hippel-Lindau Disease -- metabolism KW - Genes, Tumor Suppressor KW - Kidney Neoplasms -- metabolism KW - von Hippel-Lindau Disease -- genetics KW - Kidney Neoplasms -- etiology KW - Proteins -- metabolism KW - Proteins -- genetics KW - Carcinoma, Renal Cell -- genetics KW - von Hippel-Lindau Disease -- complications UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554958?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Protective+function+of+von+Hippel-Lindau+protein+against+impaired+protein+processing+in+renal+carcinoma+cells.&rft.au=Gorospe%2C+M%3BEgan%2C+J+M%3BZbar%2C+B%3BLerman%2C+M%3BGeil%2C+L%3BKuzmin%2C+I%3BHolbrook%2C+N+J&rft.aulast=Gorospe&rft.aufirst=M&rft.date=1999-02-01&rft.volume=19&rft.issue=2&rft.spage=1289&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - 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Last updated - 2017-01-18 ER - TY - JOUR T1 - Studies of human MDR1-MDR2 chimeras demonstrate the functional exchangeability of a major transmembrane segment of the multidrug transporter and phosphatidylcholine flippase. AN - 69553276; 9891078 AB - P-glycoprotein (P-gp), encoded by the MDR1 gene, is a plasma membrane transporter which effluxes a large number of structurally nonrelated hydrophobic compounds. The molecular basis of the broad substrate recognition of P-gp is not well understood. Despite the 78% amino acid sequence identity of the MDR1 and MDR2 transporter, MDR2, which has been identified as a phosphatidylcholine transporter, does not transport most MDR1 substrates. The structural and functional differences between MDR1 and MDR2 provide an opportunity to identify the residues essential for the broad substrate spectrum of MDR1. Using an approach involving exchanging homologous segments of MDR1 and MDR2 and site-directed mutagenesis, we have demonstrated that MDR1 residues Q330, V331, and L332 in transmembrane domain 6 are sufficient to allow an MDR2 backbone in the N-terminal half of P-gp to transport several MDR1 substrates, including bisantrene, colchicine, vinblastine, and rhodamine-123. These studies help define some residues important for multidrug transport and indicate the close functional relationship between the multidrug transporter (MDR1) and phosphatidylcholine flippase (MDR2). JF - Molecular and cellular biology AU - Zhou, Y AU - Gottesman, M M AU - Pastan, I AD - Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 1450 EP - 1459 VL - 19 IS - 2 SN - 0270-7306, 0270-7306 KW - Affinity Labels KW - 0 KW - P-Glycoprotein KW - P-Glycoproteins KW - Phosphatidylcholines KW - Recombinant Fusion Proteins KW - multidrug resistance protein 3 KW - Index Medicus KW - 3T3 Cells KW - Animals KW - HeLa Cells KW - Humans KW - Gene Expression KW - Amino Acid Sequence KW - Mice KW - Recombinant Fusion Proteins -- chemistry KW - Recombinant Fusion Proteins -- metabolism KW - Mutagenesis, Site-Directed KW - Transfection KW - Recombinant Fusion Proteins -- genetics KW - Molecular Sequence Data KW - Binding Sites -- genetics KW - Sequence Homology, Amino Acid KW - P-Glycoproteins -- chemistry KW - P-Glycoproteins -- genetics KW - P-Glycoprotein -- genetics KW - P-Glycoprotein -- metabolism KW - ATP-Binding Cassette Transporters -- metabolism KW - ATP-Binding Cassette Transporters -- genetics KW - ATP-Binding Cassette Transporters -- chemistry KW - Phosphatidylcholines -- metabolism KW - P-Glycoprotein -- chemistry KW - P-Glycoproteins -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69553276?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+biology&rft.atitle=Studies+of+human+MDR1-MDR2+chimeras+demonstrate+the+functional+exchangeability+of+a+major+transmembrane+segment+of+the+multidrug+transporter+and+phosphatidylcholine+flippase.&rft.au=Zhou%2C+Y%3BGottesman%2C+M+M%3BPastan%2C+I&rft.aulast=Zhou&rft.aufirst=Y&rft.date=1999-02-01&rft.volume=19&rft.issue=2&rft.spage=1450&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+biology&rft.issn=02707306&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-12 N1 - Date created - 1999-02-12 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122-6 [3095828] Cell. 1986 Nov 7;47(3):381-9 [2876781] Proc Natl Acad Sci U S A. 1988 Jun;85(12):4486-90 [2898143] Gene. 1988 Nov 30;71(2):401-11 [2906314] Proc Natl Acad Sci U S A. 1989 Aug;86(16):6126-30 [2548200] J Biol Chem. 1989 Sep 15;264(26):15483-8 [2475500] J Biol Chem. 1990 Mar 5;265(7):3975-80 [1968065] Mol Cell Biol. 1991 Feb;11(2):595-603 [1990275] Science. 1991 Jun 21;252(5013):1662-7 [2047875] J Biol Chem. 1991 Nov 5;266(31):20744-51 [1682313] Trends Biochem Sci. 1992 Jan;17(1):18-21 [1374941] Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5824-8 [1352877] J Biol Chem. 1992 Oct 15;267(29):21020-6 [1356986] J Biol Chem. 1992 Dec 15;267(35):25153-9 [1360983] J Biol Chem. 1993 May 25;268(15):11417-25 [8098711] Cell. 1993 Nov 5;75(3):451-62 [8106172] Cell. 1994 Jul 1;77(7):1071-81 [7912658] Cancer Res. 1994 Sep 15;54(18):4892-8 [7915194] Mol Pharmacol. 1994 Aug;46(2):329-37 [7915819] Biochemistry. 1994 Nov 29;33(47):14049-57 [7947814] J Biol Chem. 1995 Mar 10;270(10):5441-8 [7890659] Biochemistry. 1995 Apr 4;34(13):4402-11 [7535563] J Biol Chem. 1996 Apr 19;271(16):9240-8 [8621583] Annu Rev Genet. 1995;29:607-49 [8825488] Cell. 1996 Nov 1;87(3):507-17 [8898203] Mol Biol Cell. 1996 Oct;7(10):1485-98 [8898356] J Biol Chem. 1996 Nov 1;271(44):27482-7 [8910331] J Biol Chem. 1997 Aug 22;272(34):20986-9 [9261097] Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10594-9 [9380680] Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12908-13 [9371774] Biochemistry. 1998 Nov 17;37(46):16400-9 [9819232] Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785-9 [2429319] Cell. 1988 May 20;53(4):519-29 [2897240] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Addition of a missense mutation present in the L gene of respiratory syncytial virus (RSV) cpts530/1030 to RSV vaccine candidate cpts248/404 increases its attenuation and temperature sensitivity. AN - 69550038; 9882287 AB - Respiratory syncytial virus (RSV) cpts530/1030 is an attenuated, temperature-sensitive subgroup A vaccine candidate derived previously from cold-passaged RSV (cpRSV) by two sequential rounds of chemical mutagenesis and biological selection. Here, cpts530/1030 was shown to be highly attenuated in the upper and lower respiratory tracts of seronegative chimpanzees. However, evaluation in seropositive children showed that it retains sufficient replicative capacity and virulence to preclude its direct use as a live attenuated vaccine. Nucleotide sequence analysis of the genome of cpts530/1030 showed that it had acquired two nucleotide substitutions (compared to its cpts530 parent), both of which were in the L gene: a silent mutation at nucleotide position 8821 (amino acid 108) and a missense mutation at nucleotide position 12458 resulting in a tyrosine-to-asparagine change at amino acid 1321, herein referred to as the 1030 mutation. It also contained the previously identified 530 missense mutation at nucleotide 10060 in the L gene. The genetic basis of attenuation of cpts530/1030 was defined by the introduction of the 530 and 1030 mutations into a cDNA clone of cpRSV, from which recombinant RSV was derived and analyzed to determine the contribution of each mutation to the temperature sensitivity (ts) and attenuation (att) phenotypes of cpts530/1030. The 530 mutation, derived from cpts530, was previously shown to be responsible for the ts and att phenotypes of that virus. In the present study, the 1030 mutation was shown to be responsible for the increased temperature sensitivity of cpts530/1030. In addition, the 1030 mutation was shown to be responsible for the increased level of attenuation of cpts530/1030 in the upper and lower respiratory tracts of mice. The 530 and 1030 mutations were additive in their effects on the ts and att phenotypes. It was possible to introduce the 1030 mutation, but not the 530 mutation, into an attenuated vaccine candidate with residual reactogenicity in very young infants, namely, cpts248/404, by use of reverse genetics. The inability to introduce the 530 mutation into the cpts248/404 virus was shown to be due to its incompatibility with the 248 missense mutation at the level of L protein function. The resulting rA2cp248/404/1030 mutant virus was more temperature sensitive and more attenuated than the cpts248/404 parent virus, making it a promising new RSV vaccine candidate created by use of reverse genetics to improve upon an existing vaccine virus. JF - Journal of virology AU - Whitehead, S S AU - Firestone, C Y AU - Karron, R A AU - Crowe, J E AU - Elkins, W R AU - Collins, P L AU - Murphy, B R AD - Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA. sswhitehead@nih.gov Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 871 EP - 877 VL - 73 IS - 2 SN - 0022-538X, 0022-538X KW - HN Protein KW - 0 KW - Vaccines, Attenuated KW - Viral Envelope Proteins KW - Viral Proteins KW - Viral Vaccines KW - attachment protein G KW - Index Medicus KW - Virus Replication KW - Animals KW - Double-Blind Method KW - Humans KW - Temperature KW - Mice KW - Mice, Inbred BALB C KW - Sequence Analysis, DNA KW - Child, Preschool KW - Pan troglodytes KW - Infant KW - Tumor Cells, Cultured KW - Cercopithecus aethiops KW - Vero Cells KW - Viral Proteins -- immunology KW - Viral Proteins -- genetics KW - Respiratory Syncytial Virus, Human -- genetics KW - Viral Vaccines -- genetics KW - Respiratory Syncytial Virus, Human -- physiology KW - Viral Vaccines -- immunology KW - Respiratory Syncytial Virus, Human -- immunology KW - Mutation, Missense UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69550038?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Addition+of+a+missense+mutation+present+in+the+L+gene+of+respiratory+syncytial+virus+%28RSV%29+cpts530%2F1030+to+RSV+vaccine+candidate+cpts248%2F404+increases+its+attenuation+and+temperature+sensitivity.&rft.au=Whitehead%2C+S+S%3BFirestone%2C+C+Y%3BKarron%2C+R+A%3BCrowe%2C+J+E%3BElkins%2C+W+R%3BCollins%2C+P+L%3BMurphy%2C+B+R&rft.aulast=Whitehead&rft.aufirst=S&rft.date=1999-02-01&rft.volume=73&rft.issue=2&rft.spage=871&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virus Genes. 1996;13(3):269-73 [9035372] J Virol. 1997 Aug;71(8):5814-9 [9223470] J Virol. 1997 Dec;71(12):8973-82 [9371553] Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6 [9391135] J Infect Dis. 1997 Dec;176(6):1428-36 [9395351] J Virol. 1998 Mar;72(3):1762-8 [9499025] J Virol. 1998 May;72(5):4467-71 [9557743] Virology. 1979 Jan 15;92(1):155-67 [419688] Pediatrics. 1971 Nov;48(5):745-55 [4330595] Virology. 1998 Aug 1;247(2):232-9 [9705916] Infect Immun. 1982 Jul;37(1):397-400 [7107009] Methods Enzymol. 1987;154:367-82 [3323813] Vaccine. 1990 Oct;8(5):497-502 [2251875] J Immunol. 1993 Aug 15;151(4):2032-40 [8345194] Vaccine. 1993 Nov;11(14):1395-404 [8310760] Vaccine. 1994 Jun;12(8):691-9 [8091846] Vaccine. 1994 Jul;12(9):783-90 [7975856] Virology. 1995 Apr 20;208(2):478-84 [7747420] J Infect Dis. 1995 May;171(5):1107-14 [7751684] Virology. 1995 Jun 20;210(1):202-5 [7793072] J Virol. 1995 Oct;69(10):5969-77 [7666501] Vaccine. 1995 Jun;13(9):847-55 [7483808] Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11563-7 [8524804] Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):81-5 [8552680] EMBO J. 1995 Dec 15;14(24):6087-94 [8557028] J Virol. 1996 Sep;70(9):6143-50 [8709239] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Regulation of virus release by the macrophage-tropic human immunodeficiency virus type 1 AD8 isolate is redundant and can be controlled by either Vpu or Env. AN - 69549657; 9882289 AB - The human immunodeficiency virus type 1 (HIV-1) Vpu and Env proteins are expressed from a bicistronic mRNA. To address the biological significance of the coordinated expression of vpu and env, we compared the relative effects on particle release of HIV-1 isolates containing an intact vpu gene or carrying point mutations in its initiation codon or internal deletions, respectively. We found that the primary AD8 isolate, which is unable to express vpu due to a mutation in its translation initiation codon, was able to replicate in primary macrophages and peripheral blood mononuclear cells with efficiency similar to that of an isogenic variant expressing Vpu. Interestingly, AD8 lacking a vpu initiation codon produced higher levels of Env protein than its Vpu-expressing isogenic variant. In contrast, disabling Vpu without removing the vpu initiation codon did not alter Env expression but significantly reduced virus production. AD8 Env when provided in trans was capable of enhancing release not only of AD8 particles but also of viruses of the T-cell-tropic NL4-3 isolate. We conclude that AD8 Env encodes a Vpu-like activity similar to that previously reported for HIV-2 Env proteins and is thus able to augment virus secretion. When expressed at elevated levels, i.e., following mutation of the vpu initiation codon, AD8 Env was able to compensate for the lack of Vpu and thereby ensure efficient virus release. Thus, the ability to regulate virus release is redundant in AD8 and can be controlled by either Vpu or Env. Since Vpu controls several independent functions, including CD4 degradation, our results suggest that some HIV-1 isolates may have evolved a mechanism to regulate Vpu activity without compromising their ability to efficiently replicate in the host cells. JF - Journal of virology AU - Schubert, U AU - Bour, S AU - Willey, R L AU - Strebel, K AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0460, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 887 EP - 896 VL - 73 IS - 2 SN - 0022-538X, 0022-538X KW - Gene Products, env KW - 0 KW - Human Immunodeficiency Virus Proteins KW - Viral Regulatory and Accessory Proteins KW - vpu protein, Human immunodeficiency virus 1 KW - Index Medicus KW - AIDS/HIV KW - Virus Replication KW - Base Sequence KW - Leukocytes, Mononuclear -- virology KW - Transfection KW - HeLa Cells KW - Cells, Cultured KW - Humans KW - Molecular Sequence Data KW - Gene Expression KW - Amino Acid Sequence KW - Leukocytes, Mononuclear -- cytology KW - Mutagenesis KW - Macrophages -- cytology KW - HIV-1 -- genetics KW - Gene Products, env -- physiology KW - Viral Regulatory and Accessory Proteins -- physiology KW - HIV-1 -- isolation & purification KW - Macrophages -- virology KW - HIV-1 -- physiology KW - Gene Products, env -- biosynthesis KW - Viral Regulatory and Accessory Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69549657?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Regulation+of+virus+release+by+the+macrophage-tropic+human+immunodeficiency+virus+type+1+AD8+isolate+is+redundant+and+can+be+controlled+by+either+Vpu+or+Env.&rft.au=Schubert%2C+U%3BBour%2C+S%3BWilley%2C+R+L%3BStrebel%2C+K&rft.aulast=Schubert&rft.aufirst=U&rft.date=1999-02-01&rft.volume=73&rft.issue=2&rft.spage=887&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: J Cell Biol. 1989 Feb;108(2):229-41 [2645293] Cell. 1988 Dec 23;55(6):1159-69 [3060262] Proc Natl Acad Sci U S A. 1989 Jul;86(13):5163-7 [2472639] J Virol. 1990 Feb;64(2):621-9 [2404139] Proc Natl Acad Sci U S A. 1990 Jan;87(2):648-52 [2300552] Virology. 1990 Apr;175(2):465-76 [2183468] J Virol. 1990 Nov;64(11):5448-56 [2214021] J Virol. 1990 Nov;64(11):5585-93 [2214026] J Virol. 1990 Dec;64(12):6297-304 [2243395] AIDS Res Hum Retroviruses. 1990 Oct;6(10):1157-61 [1701314] J Virol. 1991 Dec;65(12):6387-96 [1942241] J Virol. 1992 Jan;66(1):226-34 [1727486] J Virol. 1992 Mar;66(3):1354-60 [1738194] Science. 1992 Jul 10;257(5067):255-9 [1321498] J Virol. 1992 Dec;66(12):7193-200 [1433512] J Acquir Immune Defic Syndr. 1993 Feb;6(2):135-41 [8094456] Virology. 1993 Apr;193(2):661-71 [7681610] J Virol. 1993 Aug;67(8):5056-61 [8331740] Microbiol Rev. 1995 Mar;59(1):63-93 [7708013] J Virol. 1994 Feb;68(2):1207-12 [8289353] Cell. 1995 Jul 28;82(2):189-92 [7628010] Curr Top Microbiol Immunol. 1995;193:107-20 [7648871] J Virol. 1993 Nov;67(11):6365-78 [8411338] J Virol. 1995 Jul;69(7):4095-102 [7769667] J Virol. 1995 Nov;69(11):7061-7 [7474126] Virology. 1995 Nov 10;213(2):639-49 [7491787] Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):494-8 [8290553] J Virol. 1994 Apr;68(4):2260-71 [8139011] J Virol. 1994 Nov;68(11):7115-23 [7933093] J Virol. 1995 Dec;69(12):7699-711 [7494279] J Virol. 1996 Feb;70(2):809-19 [8551619] J Virol. 1996 Feb;70(2):820-9 [8551620] J Virol. 1996 Feb;70(2):966-75 [8551637] J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jan 1;8(1):10-22 [8548340] J Virol. 1996 Apr;70(4):2669-73 [8642705] J Virol. 1996 Sep;70(9):6044-53 [8709227] Curr Top Microbiol Immunol. 1996;214:25-63 [8791724] J Virol. 1996 Oct;70(10):7108-15 [8794357] AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):191-4 [8835195] FEBS Lett. 1996 Nov 25;398(1):12-8 [8946945] J Virol. 1996 Dec;70(12):8285-300 [8970948] J Gen Virol. 1997 Mar;78 ( Pt 3):619-25 [9049413] Virology. 1997 Mar 3;229(1):1-11 [9123850] Nat Med. 1997 Apr;3(4):389-94 [9095171] J Exp Med. 1997 Apr 7;185(7):1295-305 [9104816] AIDS Res Hum Retroviruses. 1997 Jun 10;13(9):743-50 [9171218] Virology. 1997 May 26;232(1):207-16 [9185604] J Virol. 1998 Mar;72(3):2280-8 [9499087] Mol Cell. 1998 Mar;1(4):565-74 [9660940] J Virol. 1999 Jan;73(1):778-82 [9847387] Nature. 1988 Jan 21;331(6153):280-3 [2447506] Proc Natl Acad Sci U S A. 1985 Jul;82(13):4539-43 [2989831] J Virol. 1986 Aug;59(2):284-91 [3016298] J Virol. 1988 Jan;62(1):139-47 [3257102] Science. 1988 Sep 2;241(4870):1221-3 [3261888] J Virol. 1989 Jun;63(6):2674-9 [2786089] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Envelope formation is blocked by mutation of a sequence related to the HKD phospholipid metabolism motif in the vaccinia virus F13L protein. AN - 69547780; 9882312 AB - The outer envelope of the extracellular form of vaccinia virus is derived from Golgi membranes that have been modified by the insertion of specific viral proteins, of which the major component is the 37-kDa, palmitylated, nonglycosylated product of the F13L gene. The F13L protein contains a variant of the HKD (His-Lys-Asp) motif, which is conserved in numerous enzymes of phospholipid metabolism. Vaccinia virus mutants with a conservative substitution of either the K (K314R) or the D (D319E) residue of the F13L protein formed only tiny plaques similar to those produced by an F13L deletion mutant, were unable to produce extracellular enveloped virions, and failed to mediate low-pH-induced fusion of infected cells. Membrane-wrapped forms of intracellular virus were rarely detected in electron microscopic images of cells infected with either of the mutants. Western blotting and pulse-chase experiments demonstrated that the D319E protein was less stable than either the K314R or wild-type F13L protein. Most striking, however, was the failure of either of the two mutated proteins to concentrate in the Golgi compartment. Palmitylation, oleation, and partitioning of the F13L protein in Triton X-114 detergent were unaffected by the K314R substitution. These results indicated that the F13L protein must retain the K314 and D319 for it to localize in the Golgi compartment and function in membrane envelopment of vaccinia virus. JF - Journal of virology AU - Roper, R L AU - Moss, B AD - Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0445, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 1108 EP - 1117 VL - 73 IS - 2 SN - 0022-538X, 0022-538X KW - Chlorides KW - 0 KW - Membrane Proteins KW - Phospholipids KW - Viral Envelope Proteins KW - p37 protein, Vaccinia virus KW - Cesium KW - 1KSV9V4Y4I KW - Polyethylene Glycols KW - 30IQX730WE KW - Nonidet P-40 KW - 9036-19-5 KW - cesium chloride KW - GNR9HML8BA KW - Index Medicus KW - Centrifugation, Density Gradient KW - Animals KW - Virion KW - Viral Plaque Assay KW - HeLa Cells KW - Humans KW - Phospholipids -- metabolism KW - Gene Expression KW - Rabbits KW - Amino Acid Sequence KW - Acylation KW - Mutagenesis KW - Binding Sites KW - Phenotype KW - Cell Fusion KW - Cercopithecus aethiops KW - Molecular Sequence Data KW - Cell Line KW - Virus Assembly KW - Vaccinia virus -- genetics KW - Vaccinia virus -- physiology KW - Membrane Proteins -- metabolism KW - Vaccinia virus -- ultrastructure KW - Vaccinia virus -- metabolism KW - Viral Envelope Proteins -- metabolism KW - Membrane Proteins -- genetics KW - Viral Envelope Proteins -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69547780?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+virology&rft.atitle=Envelope+formation+is+blocked+by+mutation+of+a+sequence+related+to+the+HKD+phospholipid+metabolism+motif+in+the+vaccinia+virus+F13L+protein.&rft.au=Roper%2C+R+L%3BMoss%2C+B&rft.aulast=Roper&rft.aufirst=R&rft.date=1999-02-01&rft.volume=73&rft.issue=2&rft.spage=1108&rft.isbn=&rft.btitle=&rft.title=Journal+of+virology&rft.issn=0022538X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-18 N1 - Date created - 1999-02-18 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Cited By: Virology. 1996 Nov 15;225(2):255-66 [8918911] J Virol. 1981 Sep;39(3):903-13 [7288920] J Virol. 1997 Apr;71(4):3178-87 [9060681] J Virol. 1997 May;71(5):3904-15 [9094667] Virus Res. 1997 Apr;48(1):11-8 [9140189] EMBO J. 1997 Aug 1;16(15):4519-30 [9303296] J Gen Virol. 1980 Sep;50(1):89-100 [7441216] J Virol. 1979 Nov;32(2):614-22 [501802] J Virol. 1985 Sep;55(3):651-9 [4020961] Virology. 1986 Apr 30;150(2):451-62 [3008418] J Virol. 1986 Jun;58(3):757-64 [3701927] J Virol. 1988 Mar;62(3):866-74 [3339716] Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 [3162770] Virology. 1990 Sep;178(1):81-91 [2389560] J Virol. 1990 Oct;64(10):4884-92 [2398531] Virology. 1990 Nov;179(1):247-66, 517-63 [2219722] J Virol. 1991 Jul;65(7):3435-42 [2041074] J Virol. 1991 Jul;65(7):3583-9 [2041084] Science. 1991 Jun 21;252(5013):1662-7 [2047875] J Virol. 1991 Nov;65(11):5910-20 [1920620] Virology. 1992 Mar;187(1):251-60 [1736527] J Virol. 1992 Mar;66(3):1610-21 [1738204] Virology. 1992 Jun;188(2):801-10 [1585649] J Virol. 1992 Jul;66(7):4170-9 [1602540] J Virol. 1992 Dec;66(12):7217-24 [1433514] J Cell Biol. 1993 May;121(3):521-41 [8486734] J Virol. 1993 Jun;67(6):3319-25 [8497053] Virology. 1993 Jun;194(2):627-37 [8503178] J Virol. 1993 Aug;67(8):4732-41 [8331727] J Virol. 1994 Jan;68(1):130-47 [8254722] Virology. 1994 Oct;204(1):376-90 [8091668] Virology. 1995 Oct 20;213(1):19-27 [7483262] J Virol. 1996 Jan;70(1):272-81 [8523536] J Virol. 1996 Jun;70(6):3753-62 [8648710] Protein Sci. 1996 May;5(5):914-22 [8732763] Trends Biochem Sci. 1996 Jul;21(7):242-3 [8755242] J Biol Chem. 1997 Dec 19;272(51):32042-9 [9405398] J Virol. 1998 May;72(5):4192-204 [9557708] Virology. 1998 Apr 25;244(1):20-6 [9581774] J Gen Virol. 1998 Jun;79 ( Pt 6):1415-25 [9634084] J Gen Virol. 1971 Oct;13(1):19-25 [5130569] J Gen Virol. 1971 Oct;13(1):9-17 [4108676] Virology. 1971 Dec;46(3):507-32 [4944855] Prog Med Virol. 1973;16:86-108 [4356899] J Gen Virol. 1976 Jul;32(1):63-72 [986420] Virology. 1976 Aug;73(1):43-58 [960564] J Biol Chem. 1997 Jan 17;272(3):1956-64 [8999886] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Analgesic efficacy and pharmacokinetics of ketoprofen administered into a surgical site. AN - 69507720; 11563404 AB - A series of three clinical trials in the oral surgery model evaluated the analgesic efficacy and pharmacokinetics of ketoprofen administered locally as a strategy for decreasing systemic exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). A gel formulation was administered directly into extraction sites 1 hour following oral surgery, and pain intensity was evaluated for 6 hours. Significantly less pain was seen following peripheral administration of both 10 and 30 mg ketoprofen in comparison to the placebo. In a second study, peripheral administration of the 1 mg dose resulted in greater analgesia than oral administration of the same dose formulation or the placebo. The third study demonstrated lower plasma drug levels following the peripheral route of administration in comparison to oral administration of the same dose or ingestion of a 25 mg oral capsule. These data indicate that administration of an NSAID to a peripheral site of tissue injury results in greater analgesia than oral administration and suggests the potential for less drug toxicity through lower circulating drug levels. JF - Journal of clinical pharmacology AU - Dionne, R A AU - Gordon, S M AU - Tahara, M AU - Rowan, J AU - Troullos, E AD - Pain and Neurosensory Mechanisms Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA. Y1 - 1999/02// PY - 1999 DA - February 1999 SP - 131 EP - 138 VL - 39 IS - 2 SN - 0091-2700, 0091-2700 KW - Analgesics, Non-Narcotic KW - 0 KW - Anti-Inflammatory Agents, Non-Steroidal KW - Gels KW - Ketoprofen KW - 90Y4QC304K KW - Index Medicus KW - Administration, Oral KW - Analysis of Variance KW - Double-Blind Method KW - Humans KW - Anti-Inflammatory Agents, Non-Steroidal -- blood KW - Anti-Inflammatory Agents, Non-Steroidal -- administration & dosage KW - Tooth Extraction -- methods KW - Anti-Inflammatory Agents, Non-Steroidal -- pharmacokinetics KW - Adult KW - Adolescent KW - Male KW - Administration, Topical KW - Female KW - Analgesics, Non-Narcotic -- pharmacokinetics KW - Ketoprofen -- administration & dosage KW - Pain, Postoperative -- blood KW - Ketoprofen -- blood KW - Ketoprofen -- pharmacokinetics KW - Pain, Postoperative -- drug therapy KW - Pain Measurement -- drug effects KW - Analgesics, Non-Narcotic -- administration & dosage KW - Analgesics, Non-Narcotic -- blood UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69507720?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+clinical+pharmacology&rft.atitle=Analgesic+efficacy+and+pharmacokinetics+of+ketoprofen+administered+into+a+surgical+site.&rft.au=Dionne%2C+R+A%3BGordon%2C+S+M%3BTahara%2C+M%3BRowan%2C+J%3BTroullos%2C+E&rft.aulast=Dionne&rft.aufirst=R&rft.date=1999-02-01&rft.volume=39&rft.issue=2&rft.spage=131&rft.isbn=&rft.btitle=&rft.title=Journal+of+clinical+pharmacology&rft.issn=00912700&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 2001-10-11 N1 - Date created - 2001-09-20 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - MGZN T1 - Arthritis pain AN - 215880293; 04180694 AB - The term arthritis often represents a group of more than 100 rheumatic illnesses, which are divided into the two categories of acute and chronic. Acute is short-term pain, and chronic is long-term, requiring pain management and drug therapy. JF - Healthline AU - National Institute of Arthritis and Musculoskeletal and Skin Diseases Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 8 EP - 9 CY - Menlo Park PB - Healthline Publishers, Inc. VL - 18 IS - 2 KW - Public Health And Safety KW - Arthritis KW - Rheumatism KW - Pain management KW - Chronic illnesses KW - Drug therapy UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215880293?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Healthline&rft.atitle=Arthritis+pain&rft.au=National+Institute+of+Arthritis+and+Musculoskeletal+and+Skin+Diseases&rft.aulast=National+Institute+of+Arthritis+and+Musculoskeletal+and+Skin+Diseases&rft.aufirst=&rft.date=1999-02-01&rft.volume=18&rft.issue=2&rft.spage=8&rft.isbn=&rft.btitle=&rft.title=Healthline&rft.issn=07367929&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright Healthline Publishers, Inc. Feb 1999 N1 - Last updated - 2014-05-21 ER - TY - MGZN T1 - Questions and answers about St. John's Wort AN - 215869703; 04180688 AB - The NIH and The National Institute of Mental Health (NIMH) are conducting a large-scale clinical trial of St. John's Wort, an herbal extract used to treat depression. The NIMH concluded that studies should assess the risk of relapse and the occurrence of side effects. JF - Healthline AU - National Institute of Mental Health Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 10 CY - Menlo Park PB - Healthline Publishers, Inc. VL - 18 IS - 2 KW - Public Health And Safety KW - Herbs KW - Clinical trials KW - Mental depression KW - Antidepressants UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/215869703?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Ahealthcompleteshell&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Healthline&rft.atitle=Questions+and+answers+about+St.+John%27s+Wort&rft.au=National+Institute+of+Mental+Health&rft.aulast=National+Institute+of+Mental+Health&rft.aufirst=&rft.date=1999-02-01&rft.volume=18&rft.issue=2&rft.spage=10&rft.isbn=&rft.btitle=&rft.title=Healthline&rft.issn=07367929&rft_id=info:doi/ LA - English DB - ProQuest Central; ProQuest Environmental Science Collection N1 - Copyright - Copyright Healthline Publishers, Inc. Feb 1999 N1 - Last updated - 2014-05-21 ER - TY - JOUR T1 - Cell cycle control, checkpoint mechanisms, and genotoxic stress. AN - 21259084; 11702195 AB - The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper G1, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[a]pyrene, elicit cell cycle checkpoint responses that show both similarities and differences in their molecular signaling. Images Figure 3 JF - Environmental Health Perspectives AU - Shackelford, R E AU - Kaufmann, W K AU - Paules, R S AD - Growth Control and Cancer Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 5 EP - 24 PB - US Government Printing Office, Superintendent of Documents, P.O. Box 371954 Pittsburgh PA 15250-7954 USA VL - 107 IS - Suppl 1 SN - 0091-6765, 0091-6765 KW - Environment Abstracts KW - Mortality KW - Ionizing radiation KW - Reviews KW - Genotoxicity KW - DNA KW - Stress KW - survival KW - Cancer KW - Maintenance KW - ENA 02:Toxicology & Environmental Safety UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/21259084?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aenvabstractsmodule&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Health+Perspectives&rft.atitle=Cell+cycle+control%2C+checkpoint+mechanisms%2C+and+genotoxic+stress.&rft.au=Shackelford%2C+R+E%3BKaufmann%2C+W+K%3BPaules%2C+R+S&rft.aulast=Shackelford&rft.aufirst=R&rft.date=1999-02-01&rft.volume=107&rft.issue=Suppl+1&rft.spage=5&rft.isbn=&rft.btitle=&rft.title=Environmental+Health+Perspectives&rft.issn=00916765&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2010-01-01 N1 - Last updated - 2015-03-31 N1 - SubjectsTermNotLitGenreText - Mortality; Reviews; Ionizing radiation; Genotoxicity; DNA; Stress; survival; Maintenance; Cancer ER - TY - JOUR T1 - Neural Modeling and Functional Brain Imaging: The Interplay between the Data-Fitting and Simulation Approaches AN - 20535095; 8067764 JF - International Journal of Radiation Oncology, Biology, & Physics AU - Horwitz, Barry AU - Glabus, Michael F AD - Section on Brain Imaging and Modeling, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland 20892 Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 267 EP - 290 PB - Elsevier Science, Box 882 New York NY 10159 USA, [mailto:usinfo-f@elsevier.com] VL - 43 IS - 3 SN - 0360-3016, 0360-3016 KW - Biotechnology and Bioengineering Abstracts KW - Neuroimaging KW - W 30910:Imaging UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/20535095?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.atitle=Neural+Modeling+and+Functional+Brain+Imaging%3A+The+Interplay+between+the+Data-Fitting+and+Simulation+Approaches&rft.au=Horwitz%2C+Barry%3BGlabus%2C+Michael+F&rft.aulast=Horwitz&rft.aufirst=Barry&rft.date=1999-02-01&rft.volume=43&rft.issue=3&rft.spage=267&rft.isbn=&rft.btitle=&rft.title=International+Journal+of+Radiation+Oncology%2C+Biology%2C+%26+Physics&rft.issn=03603016&rft_id=info:doi/10.1016%2FS0074-7742%2805%2966009-6 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2008-04-01 N1 - Last updated - 2015-03-27 N1 - SubjectsTermNotLitGenreText - Neuroimaging DO - http://dx.doi.org/10.1016/S0074-7742(05)66009-6 ER - TY - JOUR T1 - Risk assessment. Characterization of inhaled alpha -methylstyrene vapor toxicity for B6C3F1 mice and F344 rats AN - 17403880; 4635867 AB - alpha -Methylstyrene (AMS) is a chemical intermediate used in the synthesis of speciality polymers and copolymers. Inhalation studies of AMS were conducted because of the lack of toxicity data and the structural similarity of AMS to styrene, a toxic and potentially carcinogenic chemical. Male and female B6C3F1 mice were exposed to 0, 600, 800, or 1000 ppm AMS 6 h/day, 5 days/week, for 12 days. After 1 exposure, 21% (5/24) of female mice were found dead in the 1000-ppm group, 56% (10/18) in the 800-ppm group, and 6% (1/18) in the 600-ppm concentration group. After 12 exposures, relative liver weights were significantly increased and relative spleen weights were significantly decreased in both male and female mice at all concentrations. No microscopic treatment-related lesions were observed. A decrease in hepatic glutathione (GSH) was associated with AMS exposure for 1 and 5 days. Male and female F344 rats were exposed to 0, 600 or 1000 ppm AMS for 12 days. No mortality or sedation occurred in AMS-exposed rats. Relative liver weights were significantly increased in both males and females after 12 exposures to 600 or 1000 ppm. An increased hyaline droplet accumulation was detected in male rats in both concentration groups; no significant microscopic lesions were observed in other tissues examined. Exposure of male and female F344 rats and male NBR rats to 0, 125, 250 or 500 ppm AMS, 6 h/day for 9 days resulted in increased accumulation of hyaline droplets in the renal tubules of male F344 rats in the 250 and 500 ppm concentration groups. Although AMS and styrene are structurally very similar, AMS was considerably less toxic for mice and more toxic for male rats than styrene. JF - Toxicological Sciences AU - Morgan, D L AU - Mahler, F J AU - Kirkpatrick, D T AU - Price, H C AU - O'Connor, R W AU - Wilson, R E AU - Moorman, M P AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA, morgand@niehs.nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 187 EP - 194 VL - 47 IS - 2 SN - 1096-6080, 1096-6080 KW - mice KW - rats KW - alpha -Methylstyrene KW - Toxicology Abstracts KW - ^a-Methylstyrene KW - Inhalation KW - Risk assessment KW - Liver KW - Spleen KW - X 24152:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17403880?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicological+Sciences&rft.atitle=Risk+assessment.+Characterization+of+inhaled+alpha+-methylstyrene+vapor+toxicity+for+B6C3F1+mice+and+F344+rats&rft.au=Morgan%2C+D+L%3BMahler%2C+F+J%3BKirkpatrick%2C+D+T%3BPrice%2C+H+C%3BO%27Connor%2C+R+W%3BWilson%2C+R+E%3BMoorman%2C+M+P&rft.aulast=Morgan&rft.aufirst=D&rft.date=1999-02-01&rft.volume=47&rft.issue=2&rft.spage=187&rft.isbn=&rft.btitle=&rft.title=Toxicological+Sciences&rft.issn=10966080&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Liver; Spleen; Risk assessment; Inhalation ER - TY - JOUR T1 - Alloimmunization for immune-based therapy and vaccine design against HIV/AIDS AN - 17386126; 4612921 AB - Recent studies have demonstrated protective effects of alloimmunization in the SIV model. Here, Gene Shearer, Ligia Pinto and Mario Clerici raise the possibility that alloimmunization against a spectrum of HLA-disparate leukocytes be considered for immune-based therapy and as an AIDS vaccine. JF - Immunology Today AU - Shearer, G M AU - Pinto, LA AU - Clerici, M AD - Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA, Gene_Shearer@nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 66 EP - 71 VL - 20 IS - 2 SN - 0167-5699, 0167-5699 KW - man KW - immunology KW - HIV KW - SIV KW - histocompatibility antigen HLA KW - human immunodeficiency virus 1 KW - Biotechnology and Bioengineering Abstracts; Virology & AIDS Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Acquired immune deficiency syndrome KW - Immunotherapy KW - Leukocytes KW - Immunization KW - Isoimmunization KW - Human immunodeficiency virus KW - Reviews KW - Vaccines KW - Simian immunodeficiency virus KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22097:Immunization: Vaccines & vaccination: Human KW - W3 33000:General topics and reviews KW - W 30965:Miscellaneous, Reviews KW - F 06860:CMI UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17386126?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Immunology+Today&rft.atitle=Alloimmunization+for+immune-based+therapy+and+vaccine+design+against+HIV%2FAIDS&rft.au=Shearer%2C+G+M%3BPinto%2C+LA%3BClerici%2C+M&rft.aulast=Shearer&rft.aufirst=G&rft.date=1999-02-01&rft.volume=20&rft.issue=2&rft.spage=66&rft.isbn=&rft.btitle=&rft.title=Immunology+Today&rft.issn=01675699&rft_id=info:doi/10.1016%2FS0167-5699%2898%2901392-9 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Simian immunodeficiency virus; Human immunodeficiency virus; Immunotherapy; Vaccines; Acquired immune deficiency syndrome; Reviews; Immunization; Leukocytes; Isoimmunization DO - http://dx.doi.org/10.1016/S0167-5699(98)01392-9 ER - TY - JOUR T1 - Solution structure of the 40,000 M sub(r) phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr AN - 17376633; 4563640 AB - The solution structure of the first protein-protein complex of the bacterial phosphoenolpyruvate: sugar phosphotransferase system between the N-terminal domain of enzyme I (EIN) and the histidine-containing phosphocarrier protein HPr has been determined by NMR spectroscopy, including the use of residual dipolar couplings that provide long-range structural information. The complex between EIN and HPr is a classical example of surface complementarity, involving an essentially all helical interface, comprising helices 2, 2', 3 and 4 of the alpha -subdomain of EIN and helices 1 and 2 of HPr, that requires virtually no changes in conformation of the components relative to that in their respective free states. The specificity of the complex is dependent on the correct placement of both van der Waals and electrostatic contacts. The transition state can be formed with minimal changes in overall conformation, and is stabilized in favor of phosphorylated HPr, thereby accounting for the directionality of phosphoryl transfer. JF - Nature Structural Biology AU - Garrett, D S AU - Seok, Yeong-Jae AU - Peterkofsky, A AU - Gronenborn, A M AU - Clore, G M AD - Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesd, MD 20892-0520, USA, clore@speck.niddk.nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 166 EP - 173 VL - 6 IS - 2 SN - 1072-8368, 1072-8368 KW - HPr protein KW - pyruvate synthase KW - pyruvate-ferredoxin oxidoreductase KW - Microbiology Abstracts B: Bacteriology KW - Pyruvate dehydrogenase (lipoamide) KW - Desulfovibrio africanus KW - Crystal structure KW - Anaerobic bacteria KW - J 02728:Enzymes UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17376633?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Structural+Biology&rft.atitle=Solution+structure+of+the+40%2C000+M+sub%28r%29+phosphoryl+transfer+complex+between+the+N-terminal+domain+of+enzyme+I+and+HPr&rft.au=Garrett%2C+D+S%3BSeok%2C+Yeong-Jae%3BPeterkofsky%2C+A%3BGronenborn%2C+A+M%3BClore%2C+G+M&rft.aulast=Garrett&rft.aufirst=D&rft.date=1999-02-01&rft.volume=6&rft.issue=2&rft.spage=166&rft.isbn=&rft.btitle=&rft.title=Nature+Structural+Biology&rft.issn=10728368&rft_id=info:doi/10.1038%2F5854 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Desulfovibrio africanus; Crystal structure; Pyruvate dehydrogenase (lipoamide); Anaerobic bacteria DO - http://dx.doi.org/10.1038/5854 ER - TY - JOUR T1 - NMR Measurement of Dipolar Couplings in Proteins Aligned by Transient Binding to Purple Membrane Fragments AN - 17365103; 4548009 AB - Here, we demonstrate that a suspension of planar purple membrane (PM) fragments, containing bacteriorhodopsin (BR), can be used to yield the required weak degree of macromolecular alignment in a strong magnetic field. The magnetic susceptibility anisotropy of these PM fragments is dominated by the membrane spanning helices of BR. Their large size (diameter of 0.2 to 2 mu m) and high BR content (75%) result in essentially full alignment of individual particles at field strengths greater than or equal to 10 T. Unlike the liquid crystalline case, there is no critical lower threshold for their concentration. The PM fragments are highly negatively charged, and the average alignment of two water-soluble proteins is shown to be dominated by electrostatic interactions. The solute alignment tensor obtained in the PM medium, therefore, is expected to be quite different from that in virus- or bicelle-based liquid crystals. JF - Journal of the American Chemical Society AU - Koenig, B W AU - Hu, J-S AU - Ottiger, M AU - Bose, S AU - Hendler, R W AU - Bax, A AD - Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Cell Biology, Building 3, National Heart, Lung and Blood Institute, National Institutes of Health Bethesda, Maryland 20892-0520, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 1385 EP - 1386 VL - 121 IS - 6 SN - 0002-7863, 0002-7863 KW - Microbiology Abstracts B: Bacteriology KW - Bacteriorhodopsin KW - Electrostatic properties KW - N.M.R. KW - Purple membranes KW - J 02723:Photosynthesis, electron transport and related phenomena UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17365103?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+the+American+Chemical+Society&rft.atitle=NMR+Measurement+of+Dipolar+Couplings+in+Proteins+Aligned+by+Transient+Binding+to+Purple+Membrane+Fragments&rft.au=Koenig%2C+B+W%3BHu%2C+J-S%3BOttiger%2C+M%3BBose%2C+S%3BHendler%2C+R+W%3BBax%2C+A&rft.aulast=Koenig&rft.aufirst=B&rft.date=1999-02-01&rft.volume=121&rft.issue=6&rft.spage=1385&rft.isbn=&rft.btitle=&rft.title=Journal+of+the+American+Chemical+Society&rft.issn=00027863&rft_id=info:doi/10.1021%2Fja9837856 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - N.M.R.; Bacteriorhodopsin; Electrostatic properties; Purple membranes DO - http://dx.doi.org/10.1021/ja9837856 ER - TY - JOUR T1 - The effect of soy protein hydrolyzates on fermentation by Lactobacillus amylovorus AN - 17303288; 4537555 AB - After hydrolysis, soy protein was utilized by the lactic acid bacterium Lactobacillus amylovorus. With the addition of 0.5 and 1% of HT-Proteolytic enzyme for hydrolysis, the molecular weight of soy peptide decreased to 700 Da in 6 h and 1 h, respectively. When the soy protein hydrolysates were used as a nitrogen source, the molecular weight of soy peptide had a significant influence on the production of lactic acid by Lactobacillus amylovorus and the optimum value was determined to be similar to 700 Da. The production rate was also dependent upon the concentration of soy peptide and, with the 3% addition of 700-Da soy peptide, the concentration of lactic acid reached 51 g/litre in a medium with 5% enzyme-thinned starch. JF - Process Biochemistry AU - Hsieh, C M AU - Yang, Fan-Chiang AU - Iannotti, EL AD - Dep. Food Eng., Tungfang Junior Coll. Technology, Hu Nei, Kaohsiung, Taiwan 82901, ROC Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 173 EP - 179 PB - Elsevier VL - 34 IS - 2 SN - 0032-9592, 0032-9592 KW - soy protein KW - soy proteins KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Agricultural and Environmental Biotechnology Abstracts KW - Fermentation KW - Hydrolysis KW - Soybeans KW - Lactobacillus amylovorus KW - Hydrolysates KW - J 02732:Other cell constituents and metabolites KW - W2 32580:Fermentation and process engineering KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17303288?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Process+Biochemistry&rft.atitle=The+effect+of+soy+protein+hydrolyzates+on+fermentation+by+Lactobacillus+amylovorus&rft.au=Hsieh%2C+C+M%3BYang%2C+Fan-Chiang%3BIannotti%2C+EL&rft.aulast=Hsieh&rft.aufirst=C&rft.date=1999-02-01&rft.volume=34&rft.issue=2&rft.spage=173&rft.isbn=&rft.btitle=&rft.title=Process+Biochemistry&rft.issn=00329592&rft_id=info:doi/10.1016%2FS0032-9592%2898%2900081-8 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lactobacillus amylovorus; Hydrolysates; Fermentation; Hydrolysis; Soybeans DO - http://dx.doi.org/10.1016/S0032-9592(98)00081-8 ER - TY - JOUR T1 - Metabolic activation of diclofenac by human cytochrome P450 3A4: Role of 5-hydroxydiclofenac AN - 17257666; 4537371 AB - Cytochrome P450 2C11 in rats was recently found to metabolize diclofenac into a highly reactive product that covalently bound to this enzyme before it could diffuse away and react with other proteins. To determine whether cytochromes P450 in human liver could catalyze a similar reaction, we have studied the covalent binding of diclofenac in vitro to liver microsomes of 16 individuals. Only three of 16 samples were found by immunoblot analysis to activate diclofenac appreciably to form protein adducts in a NADPH-dependent pathway. Cytochrome P450 2C9, which catalyzes the major route of oxidative metabolism of diclofenac to produce 4 theta -hydroxydiclofenac, did not appear to be responsible for the formation of the protein adducts, because sulfaphenazole, an inhibitor of this enzyme, did not affect protein adduct formation. In contrast, troleandomycin, an inhibitor of P450 3A4, inhibited both protein adduct formation and 5-hydroxylation of diclofenac. These findings were confirmed with the use of baculovirus-expressed human P450 2C9 and P450 3A4. One possible reactive intermediate that would be expected to bind covalently to liver proteins was the p-benzoquinone imine derivative of 5-hydroxydiclofenac. This product was formed by an apparent metal-catalyzed oxidation of 5-hydroxydiclofenac that was inhibited by EDTA, glutathione, and NADPH. The p-benzoquinone imine decomposition product bound covalently to human liver microsomes in vitro in a reaction that was inhibited by GSH. In contrast, GSH did not prevent the covalent binding of diclofenac to human liver microsomes. These results suggest that for appreciable P450-mediated bioactivation of diclofenac to occur in vivo, an individual may have to have both high activities of P450 3A4 and perhaps low activities of other enzymes that catalyze competing pathways of metabolism of diclofenac. Moreover, the p-benzoquinone imine derivative of 5-hydroxydiclofenac probably has a role in covalent binding in the liver only under the conditions where levels of NADPH, GSH, and other reducing agents would be expected to be low. JF - Chemical Research in Toxicology AU - Shen, S AU - Marchick, M R AU - Davis, M R AU - Doss, G A AU - Pohl, L R AD - Molecular and Cellular Toxicology Section, NHLBI, NIH, Building 10, Room 8N110, Bethesda, MD 20892-1760, USA, pohll@gwgate.nhlbi.nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 214 EP - 222 VL - 12 IS - 2 SN - 0893-228X, 0893-228X KW - 5-hydroxydiclofenac KW - cytochrome P450 KW - diclofenac KW - man KW - Toxicology Abstracts KW - Glutathione KW - Oxidative metabolism KW - X 24114:Metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17257666?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Chemical+Research+in+Toxicology&rft.atitle=Metabolic+activation+of+diclofenac+by+human+cytochrome+P450+3A4%3A+Role+of+5-hydroxydiclofenac&rft.au=Shen%2C+S%3BMarchick%2C+M+R%3BDavis%2C+M+R%3BDoss%2C+G+A%3BPohl%2C+L+R&rft.aulast=Shen&rft.aufirst=S&rft.date=1999-02-01&rft.volume=12&rft.issue=2&rft.spage=214&rft.isbn=&rft.btitle=&rft.title=Chemical+Research+in+Toxicology&rft.issn=0893228X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Glutathione; Oxidative metabolism ER - TY - JOUR T1 - Characterization of the recD gene of Neisseria gonorrhoeae MS11 and the effect of recD inactivation on pilin variation and DNA transformation AN - 17243954; 4525756 AB - Pilin antigenic variation in Neisseria gonorrhoeae may result following intrachromosomal recombination between homologous pil genes. Despite extensive study, recA is the only previously characterized gene known to be involved in this process. In this study, the gonococcal recD gene, encoding one subunit of the putative RecBCD holoenzyme, was characterized and its role in pilip variation assessed. The complete recD gene of N. gonorrhoeae MS11 was cloned and its nucleotide sequence determined. The gonococcal recD gene complemented a defined Escherichia coli recD mutant, based on plaque formation of bacteriophage lambda and the restoration of ATP-dependent nuclease activity. Inactivation of the gonococcal recD gene had no measurable effect on cell viability or survival following UV exposure, but did decrease the frequency of DNA transformation approximately threefold. The frequency at which non-parental pilin phenotypes were spawned was 12-fold greater in MS11 recD mutants compared with the parental MS11 rec super(+) strain. Similar results were obtained using recD mutants that were not competent for DNA transformation. Complementation of the MS11 recD mutant with a wild-type recD gene copy restored the frequency of pilin phenotypic variation to approximately wild-type levels. The nucleotide changes at pilE in the recD mutants were confined to the variable regions of the gene and were similar to changes previously attributed to gene conversion. The GenBank accession number for the sequence reported in this paper is AF058330. JF - Microbiology AU - Chaussee AU - Wilson, J AU - Hill, SA AD - Laboratory of Microbial Structure and Function, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA, mchaussee@nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 389 EP - 400 VL - 145 IS - 2 SN - 1350-0872, 1350-0872 KW - nucleotide sequence KW - pilE gene KW - pilin KW - recD gene KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Neisseria gonorrhoeae KW - G 07320:Bacterial genetics KW - J 02740:Genetics and evolution UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17243954?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Microbiology&rft.atitle=Characterization+of+the+recD+gene+of+Neisseria+gonorrhoeae+MS11+and+the+effect+of+recD+inactivation+on+pilin+variation+and+DNA+transformation&rft.au=Chaussee%3BWilson%2C+J%3BHill%2C+SA&rft.aulast=Chaussee&rft.aufirst=&rft.date=1999-02-01&rft.volume=145&rft.issue=2&rft.spage=389&rft.isbn=&rft.btitle=&rft.title=Microbiology&rft.issn=13500872&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Neisseria gonorrhoeae ER - TY - JOUR T1 - Impaired Antibacterial Host Defense in Mice Lacking the N-formylpeptide Receptor AN - 17231236; 4511681 AB - N-formylpeptides derive from bacterial and mitochondrial proteins, and bind to specific receptors on mammalian phagocytes. Since binding induces chemotaxis and activation of phagocytes in vitro, it has been postulated that N- formylpeptide receptor signaling in vivo may be important in antimicrobial host defense, although direct proof has been lacking. Here we test this hypothesis in mice lacking the high affinity N-formylpeptide receptor (FPR), created by targeted gene disruption. FPR-/- mice developed normally, but had increased susceptibility to challenge with Listeria monocytogenes, as measured by increased mortality compared with wild-type littermates. FPR-/- mice also had increased bacterial load in spleen and liver 2 d after infection, which is before development of a specific cellular immune response, suggesting a defect in innate immunity. Consistent with this, neutrophil chemotaxis in vitro and neutrophil mobilization into peripheral blood in vivo in response to the prototype N-formylpeptide fMLF (formyl-methionyl-leucyl-phenylalanine) were both absent in FPR-/- mice. These results indicate that FPR functions in antibacterial host defense in vivo. JF - Journal of Experimental Medicine AU - Gao, J AU - Lee, E J AU - Murphy, P M AD - Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 657 EP - 662 VL - 189 IS - 4 SN - 1892-1007, 1892-1007 KW - FPR-/- mice KW - N-Formylpeptide receptors KW - N-formyl peptide receptors KW - antibacterial activity KW - Microbiology Abstracts B: Bacteriology; Immunology Abstracts KW - Immune response (cell-mediated) KW - Phagocytes KW - Chemotaxis KW - F 06801:Bacteria KW - J 02833:Immune response and immune mechanisms UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17231236?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Experimental+Medicine&rft.atitle=Impaired+Antibacterial+Host+Defense+in+Mice+Lacking+the+N-formylpeptide+Receptor&rft.au=Gao%2C+J%3BLee%2C+E+J%3BMurphy%2C+P+M&rft.aulast=Gao&rft.aufirst=J&rft.date=1999-02-01&rft.volume=189&rft.issue=4&rft.spage=657&rft.isbn=&rft.btitle=&rft.title=Journal+of+Experimental+Medicine&rft.issn=18921007&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immune response (cell-mediated); Chemotaxis; Phagocytes ER - TY - JOUR T1 - Induction of Protective Host Immunity to Carcinoembryonic Antigen (CEA), a Self-Antigen in CEA Transgenic Mice, by Immunizing with a Recombinant Vaccinia-CEA Virus AN - 17222754; 4503635 AB - Human carcinoembryonic antigen (CEA) is a well-characterized oncofetal glycoprotein whose overexpression by human carcinomas has been a target for cancer immunotherapy. Transgenic mice that express CEA as a self-antigen with a tissue distribution similar to that of humans have been developed. This study investigates: (a) the responsiveness of the CEA transgenic (CEA.Tg) mice to endogenous CEA or CEA administered as a whole protein in adjuvant; and (b) whether the presentation of CEA as a recombinant vaccinia virus could generate CEA-specific host immunity. By and large, the CEA.Tg mice were unresponsive to CEA, as shown by the lack of detectable CEA-specific serum antibodies and the inability to prime an in vitro splenic T-cell response to CEA. Furthermore, the administration of whole CEA protein in adjuvant to CEA.Tg mice failed to elicit either anti-CEA IgG titers or CEA-specific T-cell responses. Only weak anti-CEA IgM antibody titers were found in those mice. In contrast, CEA.Tg mice immunized with recombinant vaccinia virus expressing CEA generated relatively strong anti-CEA IgG antibody titers and demonstrated evidence of immunoglobulin class switching. These mice also developed T sub(H)1-type CEA-specific CD4 super(+) responses and CEA peptide-specific cytotoxicity. The ability to generate CEA-specific host immunity correlated with protection of the CEA.Tg mice against a challenge with CEA-expressing tumor cells. Protection against tumor growth was accomplished with no apparent immune response directed at CEA-positive normal tissues. The results demonstrate the ability to generate an effective antitumor immune response to a tumor self-antigen by immunization with a recombinant vaccinia virus. CEA.Tg mice should be an excellent experimental model to study the effects of more aggressive immunization schemes directed at established tumors with the possible development of accompanying autoimmune responses involving normal tissues. JF - Cancer Research AU - Kass, E AU - Schlom, J AU - Thompson, J AU - Guadagni, F AU - Graziano, P AU - Greiner, J W AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Room S B07, Building 10, Bethesda, MD 20892, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 676 EP - 683 VL - 59 IS - 3 SN - 0008-5472, 0008-5472 KW - transgenic mice KW - Biotechnology and Bioengineering Abstracts; Immunology Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Immunotherapy KW - Carcinoembryonic antigen KW - Carcinoma KW - Cancer patients KW - Vaccines KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17222754?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Cancer+Research&rft.atitle=Induction+of+Protective+Host+Immunity+to+Carcinoembryonic+Antigen+%28CEA%29%2C+a+Self-Antigen+in+CEA+Transgenic+Mice%2C+by+Immunizing+with+a+Recombinant+Vaccinia-CEA+Virus&rft.au=Kass%2C+E%3BSchlom%2C+J%3BThompson%2C+J%3BGuadagni%2C+F%3BGraziano%2C+P%3BGreiner%2C+J+W&rft.aulast=Kass&rft.aufirst=E&rft.date=1999-02-01&rft.volume=59&rft.issue=3&rft.spage=676&rft.isbn=&rft.btitle=&rft.title=Cancer+Research&rft.issn=00085472&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Cancer patients; Carcinoma; Carcinoembryonic antigen; Vaccines; Immunotherapy ER - TY - JOUR T1 - Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells AN - 17208612; 4500155 AB - The early mechanisms by which DNA-dependent immunization occurs remain poorly understood. We determined whether intradermal injection of a cytomegalovirus (CMV) promoter-driven plasmid encoding hen egg lysozyme (pCMV:HEL) induced sensitization against the encoded protein, and whether cutaneous dendritic cells (DC) were involved in this sensitization. Both humoral and cellular responses to HEL were observed. DC that migrated from skin explant culture 3 days after injection of pCMV:HEL DNA contained mRNA encoding HEL. They induced a 3.5-7-fold increase in [ super(3)H]thymidine incorporation by HEL protein-primed CD4 super(+) T cells compared to that induced by DC from mice injected with control plasmid. DC emigrating from skin explants recovered from pCMV:HEL injected mice also sensitized naive mice after adoptive transfer and induced the generation of CTL. Thus following DNA delivery within the dermis, DC can induce primary and secondary immune responses. JF - European Journal of Immunology AU - Bouloc, A AU - Walker, P AU - Grivel, J-C AU - Vogel, J C AU - Katz, SI AD - Dermatology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm 12N238, 10 Center Drive, MSC 1908, Bethesda, MD 20892-1908, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 446 EP - 454 VL - 29 IS - 2 SN - 0014-2980, 0014-2980 KW - DNA vaccines KW - mice KW - murine cytomegalovirus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Skin KW - Dendritic cells KW - Immune response (cell-mediated) KW - Vaccines KW - Immune response (humoral) KW - F 06840:Immunotherapy of immune diseases KW - W3 33345:DNA vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17208612?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=European+Journal+of+Immunology&rft.atitle=Immunization+through+dermal+delivery+of+protein-encoding+DNA%3A+a+role+for+migratory+dendritic+cells&rft.au=Bouloc%2C+A%3BWalker%2C+P%3BGrivel%2C+J-C%3BVogel%2C+J+C%3BKatz%2C+SI&rft.aulast=Bouloc&rft.aufirst=A&rft.date=1999-02-01&rft.volume=29&rft.issue=2&rft.spage=446&rft.isbn=&rft.btitle=&rft.title=European+Journal+of+Immunology&rft.issn=00142980&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Immune response (humoral); Dendritic cells; Immune response (cell-mediated); Vaccines; Skin ER - TY - JOUR T1 - Requirement for multiple lymphocyte subsets in protection by a live attenuated vaccine against retroviral infection AN - 17205675; 4490823 AB - Infection by live attenuated retroviruses provides excellent protection from challenge with pathogenic viruses in several animal models, but little is known about which immune effectors are necessary for protection. We examined this using adoptive transfer experiments in the Friend virus mouse model. Transfers of immune spleen cells into naive mice conferred complete protection, and transfers of purified lymphocyte subsets demonstrated that this effect required complex immune responses involving CD4 super(+) and CD8 super(+) T cells and also B cells. In addition, passive immunization experiments demonstrated that antibodies alone reduced virus loads but did not prevent infection. These findings may have implications for retroviral vaccine design in general. JF - Nature Medicine AU - Dittmer, U AU - Brooks, D M AU - Hasenkrug, K J AD - Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, 903 S. 4th St., Hamilton, Montana 59840, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 189 EP - 193 VL - 5 IS - 2 SN - 1078-8956, 1078-8956 KW - CD4 antigen KW - Friend virus KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - Animal models KW - Lymphocytes KW - Immunity (passive) KW - Retrovirus KW - Adoptive transfer KW - Vaccines KW - W3 33365:Vaccines (other) KW - F 06807:Active immunization KW - V 22098:Immunization: Vaccines & vaccination: Animal KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17205675?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Requirement+for+multiple+lymphocyte+subsets+in+protection+by+a+live+attenuated+vaccine+against+retroviral+infection&rft.au=Dittmer%2C+U%3BBrooks%2C+D+M%3BHasenkrug%2C+K+J&rft.aulast=Dittmer&rft.aufirst=U&rft.date=1999-02-01&rft.volume=5&rft.issue=2&rft.spage=189&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Friend virus; Retrovirus; Lymphocytes; Animal models; Immunity (passive); Vaccines; Adoptive transfer ER - TY - JOUR T1 - Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell-free virions from blood plasma AN - 17204833; 4490826 AB - The concentration of human immunodeficiency virus type 1 (HIV-1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status. Steady-state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell-free particles in the presence and absence of virus-specific antibodies. Here we show, by measuring virion RNA, particle-associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual-tropic virus isolate, HIV-1 sub(DH12), is very rapid in naive animals, with half-lives ranging from 13 to 26 minutes. In the presence of high-titer HIV-1 sub(DH12)-specific neutralizing antibodies, the half-life of virion RNA was considerably reduced (to 3.9-7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV-1 infectivity due to antibody binding. JF - Nature Medicine AU - Igarashi, T AU - Brown, C AU - Azadegan, A AU - Haigwood, N AU - Dimitrov, D AU - Martin, MA AU - Shibata, R AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 211 EP - 216 VL - 5 IS - 2 SN - 1078-8956, 1078-8956 KW - Gag protein KW - HIV-1 KW - human immunodeficiency virus 1 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts KW - Virions KW - Plasma KW - Cell-free system KW - Blood KW - Antibodies KW - Human immunodeficiency virus 1 KW - Neutralization KW - W3 33375:Antibodies KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17204833?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Human+immunodeficiency+virus+type+1+neutralizing+antibodies+accelerate+clearance+of+cell-free+virions+from+blood+plasma&rft.au=Igarashi%2C+T%3BBrown%2C+C%3BAzadegan%2C+A%3BHaigwood%2C+N%3BDimitrov%2C+D%3BMartin%2C+MA%3BShibata%2C+R&rft.aulast=Igarashi&rft.aufirst=T&rft.date=1999-02-01&rft.volume=5&rft.issue=2&rft.spage=211&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Plasma; Antibodies; Neutralization; Virions; Cell-free system; Blood ER - TY - JOUR T1 - Neutralizing antibody directed against the HIV-1 envelope glycoprotein can completely block HIV-1/SIV chimeric virus infections of macaque monkeys AN - 17199390; 4490825 AB - Virus-specific antibodies protect individuals against a wide variety of viral infections. To assess whether human immunodeficiency virus type 1 (HIV-1) envelope-specific antibodies confer resistance against primate lentivirus infections, we purified immunoglobulin (IgG) from chimpanzees infected with several different HIV-1 isolates, and used this for passive immunization of pig-tailed macaques. These monkeys were subsequently challenged intravenously with a chimeric simian-human immunodeficiency virus (SHIV) bearing an envelope glycoprotein derived form HIV-1 sub(DH12), a dual-tropic primary virus isolate. Here we show that anti-SHIV neutralizing activity, determined in vitro using an assay measuring loss of infectivity, is the absolute requirement for antibody-mediated protection in vivo. Using an assay that measures 100% neutralization, the titer in plasma for complete protection of the SHIV-challenged macaques was in the range of 1:5-1:8. The HIV-1-specific neutralizing antibodies studied are able to bind to native gp 120 present on infectious virus particles. Administration of non-neutralizing anti-HIV IgG neither inhibited nor enhanced a subsequent SHIV infection. JF - Nature Medicine AU - Shibata, R AU - Igarashi, T AU - Haigwood, N AU - Buckler-White, A AU - Ogert, R AU - Ross, W AU - Willey, R AU - Cho, M W AU - Martin, MA AD - Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 204 EP - 210 VL - 5 IS - 2 SN - 1078-8956, 1078-8956 KW - Envelope glycoproteins KW - HIV-1 KW - Human immunodeficiency virus 1 KW - SIV KW - macaques KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Immunology Abstracts KW - Envelopes KW - Glycoproteins KW - Neutralization KW - Antibodies KW - Immunoglobulin G KW - Immunization (passive) KW - Simian immunodeficiency virus KW - W3 33375:Antibodies KW - F 06806:Passive immunization KW - V 22003:AIDS: Immunological aspects KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17199390?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Nature+Medicine&rft.atitle=Neutralizing+antibody+directed+against+the+HIV-1+envelope+glycoprotein+can+completely+block+HIV-1%2FSIV+chimeric+virus+infections+of+macaque+monkeys&rft.au=Shibata%2C+R%3BIgarashi%2C+T%3BHaigwood%2C+N%3BBuckler-White%2C+A%3BOgert%2C+R%3BRoss%2C+W%3BWilley%2C+R%3BCho%2C+M+W%3BMartin%2C+MA&rft.aulast=Shibata&rft.aufirst=R&rft.date=1999-02-01&rft.volume=5&rft.issue=2&rft.spage=204&rft.isbn=&rft.btitle=&rft.title=Nature+Medicine&rft.issn=10788956&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Simian immunodeficiency virus; Immunoglobulin G; Glycoproteins; Immunization (passive); Antibodies; Neutralization; Envelopes ER - TY - JOUR T1 - A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection AN - 17197023; 4484948 AB - The pharmacokinetics, toxicity, and activity of KNI-272, a transition state inhibitor of HIV-1 protease, was assessed in a phase I trial. After an initial phase in which the pharmacokinetics were assessed, 37 patients with AIDS or symptomatic HIV infection and 100-400 CD4 cells/mm super(3) were entered in an escalating dose study. KNI-272 was administered four times daily for up to 12 weeks. Oral bioavailability ranged from 22 to 55% and was not appreciably different in the fasting and post-prandial state. The dose limiting toxicity was hepatic transaminase elevation; this could be reduced by escalating the dose over 4 weeks. When administered this way, the maximum tolerated oral dose was 40 mg/kg per day. At the highest two tolerated doses (26.4 and 40 mg/kg per day), there was some evidence of an anti-HIV effect with median decreases of 0.2-0.3 log sub(10) copies/ml plasma HIV RNA; these decreases persisted through 7-8 weeks of treatment. There was an upward trend in the CD4 count at the 40 mg/kg per day dose but not at other doses. Additional studies focused on approaches to improve the therapeutic index of KNI-272 may be warranted. JF - Antiviral Research AU - Humphrey, R W AU - Wyvill, K M AU - Nguyen, B Y AU - Shay, LE AU - Kohler AU - Steinberg, S M AU - Ueno, T AU - Fukasawa, T AU - Shintani, M AU - Hayashi, H AU - Mitsuya, H AU - Yarchoan, R AD - FF1HIV and AIDS Malignancy Branch, Division of Clinical Sciences, National Cancer Institute, Building 10, Rm. 12N226, NIH, Bethesda, MD 20892 USA Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 21 EP - 33 PB - Elsevier Science Ireland Ltd. VL - 41 IS - 1 SN - 0166-3542, 0166-3542 KW - HIV-1 KW - KNI-272 KW - human immunodeficiency virus 1 KW - infection KW - man KW - proteinase inhibitors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Virology & AIDS Abstracts; Toxicology Abstracts KW - Acquired immune deficiency syndrome KW - Antiviral agents KW - Human immunodeficiency virus 1 KW - Proteinase KW - Side effects KW - W3 33372:Antiviral agents KW - W 30965:Miscellaneous, Reviews KW - V 22004:AIDS: Clinical aspects KW - X 24113:Side effects UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17197023?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Antiviral+Research&rft.atitle=A+phase+I+trial+of+the+pharmacokinetics%2C+toxicity%2C+and+activity+of+KNI-272%2C+an+inhibitor+of+HIV-1+protease%2C+in+patients+with+AIDS+or+symptomatic+HIV+infection&rft.au=Humphrey%2C+R+W%3BWyvill%2C+K+M%3BNguyen%2C+B+Y%3BShay%2C+LE%3BKohler%3BSteinberg%2C+S+M%3BUeno%2C+T%3BFukasawa%2C+T%3BShintani%2C+M%3BHayashi%2C+H%3BMitsuya%2C+H%3BYarchoan%2C+R&rft.aulast=Humphrey&rft.aufirst=R&rft.date=1999-02-01&rft.volume=41&rft.issue=1&rft.spage=21&rft.isbn=&rft.btitle=&rft.title=Antiviral+Research&rft.issn=01663542&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Human immunodeficiency virus 1; Side effects; Acquired immune deficiency syndrome; Proteinase; Antiviral agents ER - TY - JOUR T1 - Lethal effect of Rickettsia rickettsii on its tick vector (Dermacentor andersoni) AN - 17192631; 4489766 AB - Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, was lethal for the majority of experimentally and transovarially infected Rocky Mountain wood ticks (Dermacentor andersoni). Overall, 94.1% of nymphs infected as larvae by feeding on rickettsemic guinea pigs died during the molt into adults and 88.3% of adult female ticks infected as nymphs died prior to feeding. In contrast, only 2.8% of uninfected larvae failed to develop into adults over two generations. Infected female ticks incubated at 4 degree C had a lower mortality (80.9%) than did those held at 21 degree C (96.8%). Rickettsiae were vertically transmitted to 39.0% of offspring, and significantly fewer larvae developed from infected ticks. The lethal effect of R. rickettsii may explain the low prevalence of infected ticks in nature and affect its enzootic maintenance. JF - Applied and Environmental Microbiology AU - Niebylski, M L AU - Peacock, M G AU - Schwan, T G AD - Rocky Mountain Laboratories, 903 S. Fourth St., Hamilton, MT 59840, tom_schwan@nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 773 EP - 778 VL - 65 IS - 2 SN - 0099-2240, 0099-2240 KW - Acari KW - Entomology Abstracts; Microbiology Abstracts B: Bacteriology KW - Mortality KW - Transmission (vertical) KW - Ixodidae KW - Vectors KW - Rocky Mountain spotted fever KW - Pathogenicity KW - Transmission (transovarial) KW - Dermacentor andersoni KW - Rickettsia rickettsii KW - J 02870:Invertebrate bacteriology KW - Z 05182:Pathology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17192631?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Applied+and+Environmental+Microbiology&rft.atitle=Lethal+effect+of+Rickettsia+rickettsii+on+its+tick+vector+%28Dermacentor+andersoni%29&rft.au=Niebylski%2C+M+L%3BPeacock%2C+M+G%3BSchwan%2C+T+G&rft.aulast=Niebylski&rft.aufirst=M&rft.date=1999-02-01&rft.volume=65&rft.issue=2&rft.spage=773&rft.isbn=&rft.btitle=&rft.title=Applied+and+Environmental+Microbiology&rft.issn=00992240&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Dermacentor andersoni; Ixodidae; Rickettsia rickettsii; Rocky Mountain spotted fever; Transmission (transovarial); Mortality; Pathogenicity; Vectors; Transmission (vertical) ER - TY - JOUR T1 - Characteristics of Pesticide Use in a Pesticide Applicator Cohort: The Agricultural Health Study AN - 17182397; 4478341 AB - Data on recent and historic pesticide use, pesticide application methods, and farm characteristics were collected from 35,879 restricted-use pesticide applicators in the first 2 years of the Agricultural Health Study, a prospective study of a large cohort of private and commercial licensed pesticide applicators that is being conducted in Iowa and North Carolina. (In Iowa, applicators are actually "certified," while in North Carolina they are "licensed"; for ease of reference the term license will be used for both states in this paper.) Commercial applicators (studied in Iowa only) apply pesticides more days per year than private applicators in either state. When the types of pesticides being used by different groups are compared using the Spearman coefficient of determination (r super(2)), we find that Iowa private and Iowa commercial applicators tend to use the same type of pesticides (r super(2)=0.88). White and nonwhite private applicators tended to use the same type of pesticides (North Carolina r super(2)=0.89), as did male and female private applicators (Iowa r super(2)=0.85 and North Carolina r super(2)=0.84). There was less similarity (r super(2)=0.50) between the types of pesticides being used by Iowa and North Carolina private applicators. A greater portion of Iowa private applicators use personal protective equipment than do North Carolina private applicators, and pesticide application methods varied by state. This heterogeneity in potential exposures to pesticides between states should be useful for subsequent epidemiologic analyses using internal comparison groups. JF - Environmental Research AU - Alavanja, M C AU - Sandler, D P AU - Mcdonnell, C J AU - Lynch, C F AU - Pennybacker, M AU - Zahm, SH AU - Mage, D T AU - Steen, W C AU - Wintersteen, W AU - Blair, A AD - Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Z0892, Maryland Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 172 EP - 179 PB - Academic Press VL - 80 IS - 2 SN - 0013-9351, 0013-9351 KW - USA, Iowa KW - USA, North Carolina KW - man KW - Toxicology Abstracts KW - Farms KW - Occupational exposure KW - Pesticide applications KW - X 24132:Chronic exposure UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17182397?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Environmental+Research&rft.atitle=Characteristics+of+Pesticide+Use+in+a+Pesticide+Applicator+Cohort%3A+The+Agricultural+Health+Study&rft.au=Alavanja%2C+M+C%3BSandler%2C+D+P%3BMcdonnell%2C+C+J%3BLynch%2C+C+F%3BPennybacker%2C+M%3BZahm%2C+SH%3BMage%2C+D+T%3BSteen%2C+W+C%3BWintersteen%2C+W%3BBlair%2C+A&rft.aulast=Alavanja&rft.aufirst=M&rft.date=1999-02-01&rft.volume=80&rft.issue=2&rft.spage=172&rft.isbn=&rft.btitle=&rft.title=Environmental+Research&rft.issn=00139351&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Farms; Occupational exposure; Pesticide applications ER - TY - JOUR T1 - Changes in the Fine Specificity of gp100 sub((209-217))-Reactive T Cells in Patients Following Vaccination with a Peptide Modified at an HLA-A2.1 Anchor Residue AN - 17168254; 4470295 AB - In a recent clinical trial, HLA-A2 super(+) melanoma patients were vaccinated with a peptide derived from the melanoma Ag gp100, which had been modified at the second position (g9-209 2M) to enhance MHC binding affinity. Vaccination led to a significant increase in lymphocyte precursors in 10 of 11 patients but did not result in objective cancer responses. We observed that some postvaccination PBMC cultures were less reactive with tumor cells than they were with g9-209 peptide-pulsed T2 cells. In contrast, g9-209-reactive tumor-infiltrating lymphocyte cultures generally reacted equally with tumor cells and g9-209 peptide-pulsed T2 cells. To investigate this difference in T cell reactivity, T cell cloids derived from the PBMC of three patients vaccinated with g9-209 2M were compared with T cell cloids isolated from g9-209-reactive TIL cultures. All of the T cell cloids obtained from TIL reacted with HLA-A2 super(+), gp100 super(+) melanoma cell lines as well as with g9-209 and g9-209 2M peptide-pulsed targets. In contrast, only 3 of 20 PBMC-derived T cell cloids reacted with melanoma cell lines in addition to g9-209 and to g9-209 2M peptide-pulsed targets. Twelve of twenty PBMC-derived cloids reacted with g9-209 and g9-209 2M peptide-pulsed targets but not with melanoma cell lines. And 5 of 20 PBMC-derived cloids recognized only the g9-209 2M-modified peptide-pulsed targets. These results suggest that immunizing patients with the modified peptide affected the T cell repertoire by expanding an array of T cells with different fine specificities, only some of which recognized melanoma cells. JF - Journal of Immunology AU - Clay, T M AU - Custer, M C AU - McKee, MD AU - Parkhurst, M AU - Robbins, P F AU - Kerstann, K AU - Wunderlich, J AU - Rosenberg, SA AU - Nishimura, MI AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10/2B06, 9000 Rockville Pike, Bethesda, MD 20892, USA, nishimur@helix.nih.gov Y1 - 1999/02/01/ PY - 1999 DA - 1999 Feb 01 SP - 1749 EP - 1755 VL - 162 IS - 3 SN - 0022-1767, 0022-1767 KW - cancer vaccines KW - glycoprotein gp100 KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts; Immunology Abstracts KW - Antigen (tumor-associated) KW - Melanoma KW - F 06818:Cancer immunotherapy KW - W3 33350:Cancer vaccines KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17168254?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Immunology&rft.atitle=Changes+in+the+Fine+Specificity+of+gp100+sub%28%28209-217%29%29-Reactive+T+Cells+in+Patients+Following+Vaccination+with+a+Peptide+Modified+at+an+HLA-A2.1+Anchor+Residue&rft.au=Clay%2C+T+M%3BCuster%2C+M+C%3BMcKee%2C+MD%3BParkhurst%2C+M%3BRobbins%2C+P+F%3BKerstann%2C+K%3BWunderlich%2C+J%3BRosenberg%2C+SA%3BNishimura%2C+MI&rft.aulast=Clay&rft.aufirst=T&rft.date=1999-02-01&rft.volume=162&rft.issue=3&rft.spage=1749&rft.isbn=&rft.btitle=&rft.title=Journal+of+Immunology&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Melanoma; Antigen (tumor-associated) ER - TY - JOUR T1 - Performance characteristics of an enzyme-linked immunosorbent assay for determining salivary immunoglobulin G response to Helicobacter pylori AN - 17159919; 4449565 AB - We evaluated the salivary immunoglobulin G (IgG) immune response to Helicobacter pylori in 70 subjects by enzyme-linked immunosorbent assay (ELISA). Subjects with a positive H. pylori culture showed significantly higher titers of antibodies than subjects with no detectable H. pylori: the overall sensitivity and specificity of the test were 84 and 90%, respectively. The detection of salivary anti-H. pylori IgG antibodies may be considered as an alternative to serum IgG detection for ease of sample collection or when blood samples are not available in screening of patients with dyspepsia. JF - Journal of Clinical Microbiology AU - De Pascalis, R AU - Del Pezzo, M AU - Nardone, G AU - Budillon, G AU - Lavitola, A AD - Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. 5B38, 9000 Rockville Pike, Bethesda, MD 20892, USA, pascalir@mail.nih.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 430 EP - 432 VL - 37 IS - 2 SN - 0095-1137, 0095-1137 KW - Helicobacter pylori KW - man KW - Biotechnology and Bioengineering Abstracts; Microbiology Abstracts B: Bacteriology; Medical and Pharmaceutical Biotechnology Abstracts KW - Enzyme-linked immunosorbent assay KW - Immunoglobulin G KW - Saliva KW - J 02831:Techniques and reagents KW - W3 33120:Receptor based (antibodies, etc.) KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17159919?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Clinical+Microbiology&rft.atitle=Performance+characteristics+of+an+enzyme-linked+immunosorbent+assay+for+determining+salivary+immunoglobulin+G+response+to+Helicobacter+pylori&rft.au=De+Pascalis%2C+R%3BDel+Pezzo%2C+M%3BNardone%2C+G%3BBudillon%2C+G%3BLavitola%2C+A&rft.aulast=De+Pascalis&rft.aufirst=R&rft.date=1999-02-01&rft.volume=37&rft.issue=2&rft.spage=430&rft.isbn=&rft.btitle=&rft.title=Journal+of+Clinical+Microbiology&rft.issn=00951137&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Helicobacter pylori; Immunoglobulin G; Saliva; Enzyme-linked immunosorbent assay ER - TY - JOUR T1 - Maternal expenditure in the polygynous and monomorphic guanaco: suckling behavior, reproductive effort, yearly variation, and influence on juvenile survival AN - 17150005; 4450732 AB - We investigated patterns of maternal expenditure and its influence on juvenile survival in the polygynous monomorphic guanaco (Lama guanicoe) in southern Chile from 1990 to 1994. Birth weight and growth rate (until age 1) of males and females were similar. Suckling rates of males and females were not significantly different, although mothers of males rejected suckling attempts more often than mothers of females during fall and winter. Mothers with sons terminated suckling bouts in equal proportion as did mothers with daughters. Our estimated level of reproductive effort for guanacos falls within the range of species exhibiting no sex-biased maternal expenditure on offspring. Mean yearly birth weight was negatively correlated with population density. Mean suckling time throughout the year differed among cohorts, as did the mean number of suckling attempts and rejected suckling attempts per hour throughout the year. Juvenile survival was estimated until age 1. Of the model with five covariates including juvenile sex, birth weight, adult female aggression toward taggers, mean suckling time, and population density, only mean suckling time and population density were significantly related to survival. The risk ratio for mean suckling time indicates that the risk of mortality increases as suckling time increases, whereas the risk ratio for population density indicates that the risk of mortality decreases as population density increases. Under some conditions increasing population density may be correlated with lower offspring birth weight, yet enhanced juvenile survival. This effect on survival was possibly associated with the number of predators on the study area from year to year. JF - Behavioral Ecology AU - Sarno, R J AU - Franklin, W L AD - Laboratory of Genomic Diversity, FCRDC/NCI, Building 560, Room 11-12, Frederick, MD 21702-1201, USA, rjsarno@mail.ncifcrf.gov Y1 - 1999/02// PY - 1999 DA - Feb 1999 SP - 41 EP - 47 VL - 10 IS - 1 SN - 1045-2249, 1045-2249 KW - Chile KW - Animal Behavior Abstracts; Ecology Abstracts KW - Suckling behavior KW - Survival KW - Maternal behavior KW - Reproductive effort KW - Energy expenditure KW - Lama guanicoe KW - D 04672:Mammals KW - Y 25447:Mammals (excluding primates) UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17150005?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Aecology&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Behavioral+Ecology&rft.atitle=Maternal+expenditure+in+the+polygynous+and+monomorphic+guanaco%3A+suckling+behavior%2C+reproductive+effort%2C+yearly+variation%2C+and+influence+on+juvenile+survival&rft.au=Sarno%2C+R+J%3BFranklin%2C+W+L&rft.aulast=Sarno&rft.aufirst=R&rft.date=1999-02-01&rft.volume=10&rft.issue=1&rft.spage=41&rft.isbn=&rft.btitle=&rft.title=Behavioral+Ecology&rft.issn=10452249&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Lama guanicoe; Reproductive effort; Energy expenditure; Survival; Maternal behavior; Suckling behavior ER - TY - JOUR T1 - Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase. AN - 69563176; 9915785 AB - 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) synthase is a bifunctional protein consisting of an NH2-terminal APS kinase and a COOH-terminal ATP sulfurylase. Both catalytic activities require ATP; the APS kinase domain involves cleavage of the beta-gamma phosphodiester bond of ATP, whereas the ATP sulfurylase domain involves cleavage of the alpha-beta phosphodiester bond of ATP. Previous mutational studies have suggested that beta-gamma phosphodiesterase activity involves a highly conserved NTP-binding P-loop motif located in the adenosine-5'-phosphosulfate kinase domain of PAPS synthases. Sequence alignment analysis of PAPS synthases and the superfamily of TagD-related nucleotidylyltransferases revealed the presence of a highly conserved HXGH motif in the ATP sulfurylase domain of PAPS synthases, a motif implicated in the alpha-beta phosphodiesterase activity of cytidylyltransferases. Thus, site-selected mutagenesis of the HXGH motif in the ATP sulfurylase domain of human PAPS synthase (amino acids 425-428) was performed to examine this possibility. Either H425A or H428A mutation produced an inactive enzyme. In contrast, a N426K mutation resulted in increased enzymatic activity. A G427A single mutant resulted in only a modest 30% reduction in catalytic activity, whereas a G427A/H428A double mutant produced an inactive enzyme. These results suggest an important role for the HXGH histidines in the ATP sulfurylase activity of bifunctional PAPS synthase and support the hypothesis that the highly conserved HXGH motif found in the ATP sulfurylase domain of PAPS synthases is involved in ATP binding and alpha-beta phosphodiesterase activity. JF - The Journal of biological chemistry AU - Venkatachalam, K V AU - Fuda, H AU - Koonin, E V AU - Strott, C A AD - Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. Y1 - 1999/01/29/ PY - 1999 DA - 1999 Jan 29 SP - 2601 EP - 2604 VL - 274 IS - 5 SN - 0021-9258, 0021-9258 KW - Multienzyme Complexes KW - 0 KW - Adenosine Triphosphate KW - 8L70Q75FXE KW - PAPS synthetase KW - EC 2.7.7.4 KW - Sulfate Adenylyltransferase KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Sequence Alignment KW - Humans KW - Adenosine Triphosphate -- metabolism KW - Molecular Sequence Data KW - Catalytic Domain -- genetics KW - Amino Acid Sequence KW - Cell Line KW - Multienzyme Complexes -- metabolism KW - Sulfate Adenylyltransferase -- metabolism KW - Conserved Sequence KW - Sulfate Adenylyltransferase -- genetics KW - Multienzyme Complexes -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69563176?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Site-selected+mutagenesis+of+a+conserved+nucleotide+binding+HXGH+motif+located+in+the+ATP+sulfurylase+domain+of+human+bifunctional+3%27-phosphoadenosine+5%27-phosphosulfate+synthase.&rft.au=Venkatachalam%2C+K+V%3BFuda%2C+H%3BKoonin%2C+E+V%3BStrott%2C+C+A&rft.aulast=Venkatachalam&rft.aufirst=K&rft.date=1999-01-29&rft.volume=274&rft.issue=5&rft.spage=2601&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-03 N1 - Date created - 1999-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Side chains that influence fidelity at the polymerase active site of Escherichia coli DNA polymerase I (Klenow fragment). AN - 69554460; 9915846 AB - To investigate the interactions that determine DNA polymerase accuracy, we have measured the fidelity of 26 mutants with amino acid substitutions in the polymerase domain of a 3'-5'-exonuclease-deficient Klenow fragment. Most of these mutant polymerases synthesized DNA with an apparent fidelity similar to that of the wild-type control, suggesting that fidelity at the polymerase active site depends on highly specific enzyme-substrate interactions and is not easily perturbed. In addition to the previously studied Y766A mutator, four novel base substitution mutators were identified; they are R668A, R682A, E710A, and N845A. Each of these five mutator alleles results from substitution of a highly conserved amino acid side chain located on the exposed surface of the polymerase cleft near the polymerase active site. Analysis of base substitution errors at four template positions indicated that each of the five mutator polymerases has its own characteristic error specificity, suggesting that the Arg-668, Arg-682, Glu-710, Tyr-766, and Asn-845 side chains may contribute to polymerase fidelity in a variety of different ways. We separated the contributions of the nucleotide insertion and mismatch extension steps by using a novel fidelity assay that scores base substitution errors during synthesis to fill a single nucleotide gap (and hence does not require mismatch extension) and by measuring the rates of polymerase-catalyzed mismatch extension reactions. The R682A, E710A, Y766A, and N845A mutations cause decreased fidelity at the nucleotide insertion step, whereas R668A results in lower fidelity in both nucleotide insertion and mismatch extension. Relative to wild type, several Klenow fragment mutants showed substantially more discrimination against extension of a T.G mismatch under the conditions of the fidelity assay, providing one explanation for the anti-mutator phenotypes of mutants such as R754A and Q849A. JF - The Journal of biological chemistry AU - Minnick, D T AU - Bebenek, K AU - Osheroff, W P AU - Turner, R M AU - Astatke, M AU - Liu, L AU - Kunkel, T A AU - Joyce, C M AD - Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA. Y1 - 1999/01/29/ PY - 1999 DA - 1999 Jan 29 SP - 3067 EP - 3075 VL - 274 IS - 5 SN - 0021-9258, 0021-9258 KW - DNA Polymerase I KW - EC 2.7.7.- KW - Index Medicus KW - Phenotype KW - Mutagenesis, Site-Directed KW - Models, Molecular KW - Amino Acid Substitution KW - Structure-Activity Relationship KW - Catalysis KW - Binding Sites KW - DNA Polymerase I -- genetics KW - Escherichia coli -- enzymology KW - DNA Polymerase I -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554460?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=The+Journal+of+biological+chemistry&rft.atitle=Side+chains+that+influence+fidelity+at+the+polymerase+active+site+of+Escherichia+coli+DNA+polymerase+I+%28Klenow+fragment%29.&rft.au=Minnick%2C+D+T%3BBebenek%2C+K%3BOsheroff%2C+W+P%3BTurner%2C+R+M%3BAstatke%2C+M%3BLiu%2C+L%3BKunkel%2C+T+A%3BJoyce%2C+C+M&rft.aulast=Minnick&rft.aufirst=D&rft.date=1999-01-29&rft.volume=274&rft.issue=5&rft.spage=3067&rft.isbn=&rft.btitle=&rft.title=The+Journal+of+biological+chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-03 N1 - Date created - 1999-03-03 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Carcinoma cell lines resistant for growth inhibition and apoptosis to retinoic acid are responsive to 4-hydroxy-phenyl-retinamide: correlation with tissue transglutaminase. AN - 69572164; 9920792 AB - Retinoic acid (RA)-resistant cell lines are highly malignant. To inhibit the growth of the RA-resistant cells we used 4-HPR, a synthetic retinoid, which may act through alternative signal transduction pathways. 4-HPR induced cell growth inhibition and apoptosis in all RA-sensitive as well as -resistant cells, demonstrating a wider spectrum of potency over RA. 4-HPR induced tissue TGase activity. A tight correlation between the induction of tissue TGase, the inhibition of cell growth, and apoptosis was evident in all eight RA-sensitive cell lines. However, basal TGase differed in the different cells, suggesting inducibility rather than basal levels as the relevant parameter. In sharp contrast to the RA-sensitive cells, RA-resistant cells showed sporadic response to 4-HPR for tissue TGase. The wider spectrum of activity of 4-HPR in inhibiting cell growth and inducing apoptosis makes it a good candidate for the treatment of RA-resistant cancer cells. JF - Biochemical and biophysical research communications AU - Chiantore, M V AU - Giandomenico, V AU - De Luca, L M AD - Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20892-4255, USA. Y1 - 1999/01/27/ PY - 1999 DA - 1999 Jan 27 SP - 636 EP - 641 VL - 254 IS - 3 SN - 0006-291X, 0006-291X KW - Fenretinide KW - 187EJ7QEXL KW - Tretinoin KW - 5688UTC01R KW - Transglutaminases KW - EC 2.3.2.13 KW - Index Medicus KW - Animals KW - 3T3 Cells KW - Tumor Cells, Cultured KW - Humans KW - Apoptosis -- drug effects KW - Cell Division -- drug effects KW - Mice KW - Tretinoin -- pharmacology KW - Transglutaminases -- metabolism KW - Fenretinide -- pharmacology KW - Carcinoma -- pathology KW - Carcinoma -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69572164?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemical+and+biophysical+research+communications&rft.atitle=Carcinoma+cell+lines+resistant+for+growth+inhibition+and+apoptosis+to+retinoic+acid+are+responsive+to+4-hydroxy-phenyl-retinamide%3A+correlation+with+tissue+transglutaminase.&rft.au=Chiantore%2C+M+V%3BGiandomenico%2C+V%3BDe+Luca%2C+L+M&rft.aulast=Chiantore&rft.aufirst=M&rft.date=1999-01-27&rft.volume=254&rft.issue=3&rft.spage=636&rft.isbn=&rft.btitle=&rft.title=Biochemical+and+biophysical+research+communications&rft.issn=0006291X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-01 N1 - Date created - 1999-03-01 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells. AN - 69680591; 10195695 AB - Previously, several members of the nuclear receptor superfamily have been implicated in the regulation of epidermal differentiation. In this study, we analyze the expression of members of the PPAR nuclear receptor subfamily in relation to the process of squamous differentiation in normal human epidermal keratinocytes (NHEK), human tracheobronchial epithelial (HBE) cells and the epidermis in vivo. Our results demonstrate that induction of differentiation in NHEK by either treatment with the phorbol ester phorbol 12-myristate-13-acetate (PMA), suspension culture or confluence greatly enhances the expression of PPARbeta mRNA. Likewise, topical treatment of mouse skin with PMA results in increased PPARbeta mRNA expression in the epidermis. In addition, the induction of squamous differentiation in HBE cells was also associated with an upregulation of PPARbeta mRNA expression. Finally, in situ hybridization analysis localized PPARbeta mRNA to the suprabasal layers of normal human skin. Our results demonstrate that the expression of PPARbeta is associated with squamous differentiation suggesting a regulatory role for this receptor in the control of specific genes during this differentiation process. JF - Molecular and cellular endocrinology AU - Matsuura, H AU - Adachi, H AU - Smart, R C AU - Xu, X AU - Arata, J AU - Jetten, A M AD - Cell Biology Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Y1 - 1999/01/25/ PY - 1999 DA - 1999 Jan 25 SP - 85 EP - 92 VL - 147 IS - 1-2 SN - 0303-7207, 0303-7207 KW - Cornified Envelope Proline-Rich Proteins KW - 0 KW - Membrane Proteins KW - RNA, Messenger KW - Receptors, Cytoplasmic and Nuclear KW - Transcription Factors KW - Transforming Growth Factor beta KW - Tretinoin KW - 5688UTC01R KW - Interferon-gamma KW - 82115-62-6 KW - Transglutaminases KW - EC 2.3.2.13 KW - Tetradecanoylphorbol Acetate KW - NI40JAQ945 KW - Index Medicus KW - Tretinoin -- pharmacology KW - Transforming Growth Factor beta -- pharmacology KW - Animals KW - Transglutaminases -- genetics KW - Humans KW - Keratinocytes -- drug effects KW - Interferon-gamma -- pharmacology KW - Mice KW - Membrane Proteins -- genetics KW - Mice, Inbred Strains KW - RNA, Messenger -- metabolism KW - Tetradecanoylphorbol Acetate -- pharmacology KW - Keratinocytes -- cytology KW - Keratinocytes -- metabolism KW - Cell Differentiation -- drug effects KW - Time Factors KW - Cell Line KW - Female KW - Epithelial Cells -- metabolism KW - Epithelial Cells -- cytology KW - Epidermis -- drug effects KW - Epithelial Cells -- drug effects KW - Bronchi -- cytology KW - Epidermis -- cytology KW - Epidermis -- metabolism KW - Transcriptional Activation -- drug effects KW - Receptors, Cytoplasmic and Nuclear -- genetics KW - Trachea -- cytology KW - Transcription Factors -- genetics UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69680591?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Molecular+and+cellular+endocrinology&rft.atitle=Correlation+between+expression+of+peroxisome+proliferator-activated+receptor+beta+and+squamous+differentiation+in+epidermal+and+tracheobronchial+epithelial+cells.&rft.au=Matsuura%2C+H%3BAdachi%2C+H%3BSmart%2C+R+C%3BXu%2C+X%3BArata%2C+J%3BJetten%2C+A+M&rft.aulast=Matsuura&rft.aufirst=H&rft.date=1999-01-25&rft.volume=147&rft.issue=1-2&rft.spage=85&rft.isbn=&rft.btitle=&rft.title=Molecular+and+cellular+endocrinology&rft.issn=03037207&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-07-06 N1 - Date created - 1999-07-06 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Free radical scavenger OPC-14117 attenuates quinolinic acid-induced NF-kappaB activation and apoptosis in rat striatum. AN - 69554743; 9889320 AB - Oxidative stress has long been implicated in the pathogenesis of both the acute and chronic neurotoxic effects of glutamate acting through ionotrophic receptors of the N-methyl-d-aspartate (NMDA) subtype. To evaluate the contribution of oxidative stress to the NMDA receptor-mediated apoptotic death of rat striatal neurons in vivo, the effects of a novel, orally administered free radical scavenger, OPC-14117, was studied following intrastriatal infusion of the NMDA receptor agonist quinolinic acid (QA). Receptor autoradiography and in situ hybridization histochemistry showed that pretreatment with OPC-14117 (600 mg/kg) reduced the QA (120 nmol)-induced loss of striatal D1 dopamine receptors by about 20% (p<0.01) and NMDA receptors by 15% (p<0.01) as well as 67 kDa glutamic acid decarboxylase mRNA (34%; p<0.01) and proenkephalin mRNA (36%; p<0.01). OPC-14117 also decreased the apomorphine-induced ipsilateral rotational response in unilaterally QA-lesioned animals by about 70% (p<0.05). In addition, OPC-14117 pretreatment inhibited QA-induced internucleosomal DNA fragmentation. Western blot analysis and electrophoresis mobility shift assay further revealed that the free radical scavenger (300 and 600 mg/kg) blunted the QA-induced degradation of IkappaBalpha (increased IkappaBalpha levels from about 15% to 33 and 62% of control, respectively; p<0.01) as well as the ensuing activation of NF-kappaB by 25 to 34%, respectively (p<0. 01) and the augmentation in c-Myc (35 to 70%, respectively) and p53 expression by 50-80%, respectively (both p<0.01). In contrast, OPC-14117 had no significant effect on the QA-induced increase in AP-1 binding activity. These results suggest that the NMDA receptor-mediated generation of reactive oxygen species contributes to the QA-induced activation of NF-kappaB and further that orally administered OPC-14117 partially protects against excitotoxin-induced apoptosis of striatal neurons through inhibition of the NF-kappaB apoptotic cascade. Copyright 1999 Elsevier Science B.V. JF - Brain research. Molecular brain research AU - Nakai, M AU - Qin, Z H AU - Wang, Y AU - Chase, T N AD - Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bldg 10, Rm. 5C103, 10 Center Drive, MSC 1406, Bethesda, MD 20892-1406, USA. Y1 - 1999/01/22/ PY - 1999 DA - 1999 Jan 22 SP - 59 EP - 68 VL - 64 IS - 1 SN - 0169-328X, 0169-328X KW - DNA-Binding Proteins KW - 0 KW - Free Radical Scavengers KW - I-kappa B Proteins KW - Indans KW - NF-kappa B KW - Neurotoxins KW - Nfkbia protein, rat KW - Piperazines KW - Proto-Oncogene Proteins c-myc KW - Receptors, N-Methyl-D-Aspartate KW - Tumor Suppressor Protein p53 KW - OPC 14117 KW - 103233-65-4 KW - NF-KappaB Inhibitor alpha KW - 139874-52-5 KW - Quinolinic Acid KW - F6F0HK1URN KW - Index Medicus KW - Animals KW - Corpus Striatum -- cytology KW - Drug Interactions KW - DNA-Binding Proteins -- pharmacology KW - Proto-Oncogene Proteins c-myc -- genetics KW - Neurotoxins -- pharmacology KW - Nerve Degeneration -- chemically induced KW - Rats KW - Gene Expression Regulation, Neoplastic KW - Nerve Degeneration -- drug therapy KW - Behavior, Animal -- drug effects KW - Receptors, N-Methyl-D-Aspartate -- physiology KW - Rats, Sprague-Dawley KW - Oxidative Stress -- physiology KW - Corpus Striatum -- chemistry KW - Protein Binding -- drug effects KW - Tumor Suppressor Protein p53 -- genetics KW - DNA Fragmentation KW - Male KW - Neurons -- chemistry KW - Neurons -- drug effects KW - Neurons -- cytology KW - Apoptosis -- drug effects KW - Indans -- pharmacology KW - Quinolinic Acid -- pharmacology KW - Piperazines -- pharmacology KW - Free Radical Scavengers -- pharmacology KW - NF-kappa B -- metabolism KW - NF-kappa B -- antagonists & inhibitors UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69554743?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research.+Molecular+brain+research&rft.atitle=Free+radical+scavenger+OPC-14117+attenuates+quinolinic+acid-induced+NF-kappaB+activation+and+apoptosis+in+rat+striatum.&rft.au=Nakai%2C+M%3BQin%2C+Z+H%3BWang%2C+Y%3BChase%2C+T+N&rft.aulast=Nakai&rft.aufirst=M&rft.date=1999-01-22&rft.volume=64&rft.issue=1&rft.spage=59&rft.isbn=&rft.btitle=&rft.title=Brain+research.+Molecular+brain+research&rft.issn=0169328X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-02 N1 - Date created - 1999-03-02 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Silencing of genes flanking the P1 plasmid centromere AN - 17162956; 4452886 AB - Partition modules stabilize bacterial plasmids and chromosomes by actively promoting their segregation into daughter cells. The partition module of plasmid P1 is typical and consists of a centromere site, parS, and genes that encode proteins ParA and ParB. We show that ParB can silence genes flanking parS (to which ParB binds), apparently by polymerizing along the DNA from a nucleation site at parS. Wild-type ParB contacts an extensive region of P1 DNA; silencing-defective ParB proteins, which where found to be partition-defective, are less able to spread. Hence, the silenced structure appears to function in partitioning. JF - Science (Washington) AU - Rodionov, O AU - Lobocka, M AU - Yarmolinsky, M AD - Lab. Biochem., Natl. Cancer Inst., 37 Convent Dr., Bethesda, MD 20892-4255, USA, myarmo@helix.nih.gov Y1 - 1999/01/22/ PY - 1999 DA - 1999 Jan 22 SP - 546 EP - 549 PB - American Association for the Advancement of Science VL - 283 IS - 5401 SN - 0036-8075, 0036-8075 KW - ParA protein KW - ParB protein KW - centromeres KW - plasmid P1 KW - Genetics Abstracts; Microbiology Abstracts B: Bacteriology KW - Gene silencing KW - J 02760:Plasmids KW - G 07203:Plasmids UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17162956?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Amicrobiologyb&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Science+%28Washington%29&rft.atitle=Silencing+of+genes+flanking+the+P1+plasmid+centromere&rft.au=Rodionov%2C+O%3BLobocka%2C+M%3BYarmolinsky%2C+M&rft.aulast=Rodionov&rft.aufirst=O&rft.date=1999-01-22&rft.volume=283&rft.issue=5401&rft.spage=546&rft.isbn=&rft.btitle=&rft.title=Science+%28Washington%29&rft.issn=00368075&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Gene silencing ER - TY - JOUR T1 - Sequence context effects on mutational properties of cis-opened benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts in site-specific mutation studies. AN - 69556286; 9894012 AB - Diastereomeric N6-substituted dAdo adducts (cis B[c]PhDE-2/1R and cis B[c]PhDE-2/1S) that correspond to cis-opening at C-1 of the enantiomeric benzo[c]phenanthrene 3,4-diol 1,2-epoxides in which the epoxide oxygen and the benzylic hydroxyl group are trans (DE-2) were synthetically incorporated into oligonucleotide 16-mers. Each adduct was placed at the fourth nucleotide from the 5'-end of each of two different oligonucleotide sequences derived from the E. coli supF gene. Each adduct was also placed in two additional oligonucleotide sequences that were constructed by interchanging the adduct site and the immediately adjacent nucleotides between the two original sequences. These oligonucleotides were designed for use in site-specific mutation studies, with a single-stranded bacteriophage M13mp7L2 vector, to determine if the effects of sequence context on types and frequencies of base substitution mutations are attributable only to nucleotides immediately adjacent to these polycyclic aromatic hydrocarbon diol epoxide-dAdo adducts, or whether more distant nucleotide residues also affect the mutagenic response. In SOS-induced Escherichia coli SMH77, total base substitution mutation frequencies for the cis B[c]PhDE-2/1R-dAdo adduct were relatively low (0.62-5.6%) compared with those for the cis B[c]PhDE-2/1S-dAdo adduct (11.9-56.5%). Depending on sequence context, cis B[c]PhDE-2/1R-dAdo gave predominantly A-->T or a more equal distribution of A-->T and A-->G mutations whereas cis B[c]PhDE-2/1S-dAdo gave either predominantly A-->T or predominantly A-->G base substitutions. Our results clearly indicate that nucleotides that are distal as well as those that are proximal to the adduct site are capable of influencing both the mutation frequency and the distribution of base substitution mutations. JF - Biochemistry AU - Pontén, I AU - Sayer, J M AU - Pilcher, A S AU - Yagi, H AU - Kumar, S AU - Jerina, D M AU - Dipple, A AD - Chemistry of Carcinogenesis Laboratory, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. Y1 - 1999/01/19/ PY - 1999 DA - 1999 Jan 19 SP - 1144 EP - 1152 VL - 38 IS - 3 SN - 0006-2960, 0006-2960 KW - DNA Adducts KW - 0 KW - Deoxyadenosines KW - Mutagens KW - Oligonucleotides KW - Phenanthrenes KW - 1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene KW - 111001-48-0 KW - Index Medicus KW - Base Sequence KW - Oligonucleotides -- chemistry KW - Electrophoresis, Polyacrylamide Gel KW - Genetic Vectors KW - DNA Mutational Analysis KW - Circular Dichroism KW - Bacteriophage M13 -- genetics KW - Oligonucleotides -- genetics KW - Chromatography, High Pressure Liquid KW - Mutagenesis, Site-Directed KW - DNA Adducts -- genetics KW - DNA Adducts -- chemistry KW - Deoxyadenosines -- genetics KW - Deoxyadenosines -- chemistry KW - Phenanthrenes -- chemistry KW - Mutagens -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69556286?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Biochemistry&rft.atitle=Sequence+context+effects+on+mutational+properties+of+cis-opened+benzo%5Bc%5Dphenanthrene+diol+epoxide-deoxyadenosine+adducts+in+site-specific+mutation+studies.&rft.au=Pont%C3%A9n%2C+I%3BSayer%2C+J+M%3BPilcher%2C+A+S%3BYagi%2C+H%3BKumar%2C+S%3BJerina%2C+D+M%3BDipple%2C+A&rft.aulast=Pont%C3%A9n&rft.aufirst=I&rft.date=1999-01-19&rft.volume=38&rft.issue=3&rft.spage=1144&rft.isbn=&rft.btitle=&rft.title=Biochemistry&rft.issn=00062960&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-23 N1 - Date created - 1999-02-23 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Bridging the gulf in war syndromes. AN - 69566284; 9923865 JF - Lancet (London, England) AU - Straus, S E AD - Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01/16/ PY - 1999 DA - 1999 Jan 16 SP - 162 EP - 163 VL - 353 IS - 9148 SN - 0140-6736, 0140-6736 KW - Abridged Index Medicus KW - Index Medicus KW - Humans KW - Persian Gulf Syndrome -- epidemiology KW - Persian Gulf Syndrome -- diagnosis KW - Persian Gulf Syndrome -- etiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69566284?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet+%28London%2C+England%29&rft.atitle=Bridging+the+gulf+in+war+syndromes.&rft.au=Straus%2C+S+E&rft.aulast=Straus&rft.aufirst=S&rft.date=1999-01-16&rft.volume=353&rft.issue=9148&rft.spage=162&rft.isbn=&rft.btitle=&rft.title=Lancet+%28London%2C+England%29&rft.issn=01406736&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-11 N1 - Date created - 1999-02-11 N1 - Date revised - 2017-01-13 N1 - SuppNotes - Comment On: Lancet. 1999 Jan 16;353(9148):179-82 [9923872] Lancet. 1999 Jan 16;353(9148):169-78 [9923871] N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Spatial memory impairment in ventral subicular lesioned rats. AN - 69552246; 9878765 AB - The present study examined the effects of ibotenic acid lesions of the ventral subiculum (SUB) on the ability of rats to memorize a rewarded alternation test in a T-maze. Results indicated that rats with ibotenic acid lesions (IL) of the ventral subiculum were impaired in postoperative acquisition of the spatial discrimination task, making more errors than the vehicle treated and normal control rats. In addition, all rats, including the IL group of rats, were able to memorize an acquired spatial behaviour. These findings suggest that the SUB play an important role in spatial information processing in rats. Copyright 1999 Elsevier Science B.V. JF - Brain research AU - Laxmi, T R AU - Bindu, P N AU - Raju, T R AU - Meti, B L AD - Department of Neurophysiology, National Institute of Mental Health and Neurosciences, P.B. 2900, Hosur Road, Bangalore-560 029, Karnataka, India. Y1 - 1999/01/16/ PY - 1999 DA - 1999 Jan 16 SP - 245 EP - 248 VL - 816 IS - 1 SN - 0006-8993, 0006-8993 KW - Ibotenic Acid KW - 2552-55-8 KW - Index Medicus KW - Retention (Psychology) -- physiology KW - Rats KW - Animals KW - Maze Learning -- physiology KW - Conditioning, Operant -- physiology KW - Ibotenic Acid -- administration & dosage KW - Rats, Wistar KW - Behavior, Animal -- physiology KW - Microinjections KW - Wakefulness KW - Male KW - Memory Disorders -- chemically induced KW - Hippocampus -- physiology KW - Spatial Behavior -- physiology KW - Memory -- physiology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69552246?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Brain+research&rft.atitle=Spatial+memory+impairment+in+ventral+subicular+lesioned+rats.&rft.au=Laxmi%2C+T+R%3BBindu%2C+P+N%3BRaju%2C+T+R%3BMeti%2C+B+L&rft.aulast=Laxmi&rft.aufirst=T&rft.date=1999-01-16&rft.volume=816&rft.issue=1&rft.spage=245&rft.isbn=&rft.btitle=&rft.title=Brain+research&rft.issn=00068993&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-25 N1 - Date created - 1999-03-25 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Sex ratio after exposure to dioxin-like chemicals in Taiwan AN - 17226877; 4506433 AB - Between 1977 and 1984, 48 girls but only 26 boys were born to parents exposed to 2,3,7,8 tetrachlorodibenzo- rho -dioxin (TCDD, or dioxin) in Seveso, Italy. The 1976 industrial accident at Seveso produced the highest documented community exposures to TCDD, and the period 1976-83 represents about one half-life of TCDD in adult human beings. Although TCDD is perhaps the most toxic and carcinogenic synthetic chemical known, has hormonal agonist/antagonist properties, and alters hormone metabolism, how it might have led to such a large departure from the expected sex ratio at birth of about 49 girls to 51 boys is unknown. Since the toxic effects are more evident and more people are likely to have had high exposures in Taiwan, and since the chemical agents seem to act through similar mechanisms, we investigated whether the sex ratio was also altered there. Despite high exposure to similar chemicals, sufficient to produce obvious clinical disease and reproductive toxic effects, the sex ratio was not altered in Taiwan. JF - Lancet AU - Rogan, W J AU - Gladen, B C AU - Guo, Y-LL AU - Hsu, C-C AD - National Institute of Environmental Health Sciences, Research Triangle Park, NC27709, USA Y1 - 1999/01/16/ PY - 1999 DA - 1999 Jan 16 SP - 206 EP - 207 VL - 353 IS - 9148 SN - 0099-5355, 0099-5355 KW - TCDD KW - Taiwan KW - man KW - Toxicology Abstracts KW - Sex ratio KW - X 24156:Environmental impact UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17226877?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Lancet&rft.atitle=Sex+ratio+after+exposure+to+dioxin-like+chemicals+in+Taiwan&rft.au=Rogan%2C+W+J%3BGladen%2C+B+C%3BGuo%2C+Y-LL%3BHsu%2C+C-C&rft.aulast=Rogan&rft.aufirst=W&rft.date=1999-01-16&rft.volume=353&rft.issue=9148&rft.spage=206&rft.isbn=&rft.btitle=&rft.title=Lancet&rft.issn=00995355&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Sex ratio ER - TY - JOUR T1 - Identification of lysine350 of yeast deoxyhypusine synthase as the site of enzyme intermediate formation. AN - 69588911; 10028184 AB - The posttranslational formation of deoxyhypusine in the precursor of eukaryotic initiation factor 5A (eIF5A) is catalysed by deoxyhypusine synthase. This NAD-dependent reaction involves transfer of the 4-aminobutyl moiety of spermidine to a single lysine residue in the eIF5A precursor. The present study shows evidence for the formation of a covalent enzyme-substrate intermediate between a specific lysine residue (Lys350) of yeast deoxyhypusine synthase and the 4-aminobutyl moiety from spermidine. Substitution of this lysine residue with Arg or Ala totally prevented the formation of the enzyme intermediate and consequently precluded deoxyhypusine synthesis in the eIF5A precursor, leading to the conclusion that the enzyme intermediate formed at Lys350 is critical for deoxyhypusine synthesis activity. The results provide a rational basis for the inability of the mutated deoxyhypusine synthase gene encoding arginine in place of Lys350 to support growth in yeast (Park et al., 1998). The demonstration of the formation of an enzyme-imine intermediate in yeast deoxyhypusine synthase analogous to that of the human enzyme strongly suggest that the enzyme mechanism is conserved in diverse eukaryotes. JF - Yeast (Chichester, England) AU - Wolff, E C AU - Park, M H AD - Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, NIH, Bethesda, MD 20892-4340, USA. ew23v@nih.gov Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 43 EP - 50 VL - 15 IS - 1 SN - 0749-503X, 0749-503X KW - Peptide Initiation Factors KW - 0 KW - hypusine KW - 3874VXF092 KW - Oxidoreductases Acting on CH-NH Group Donors KW - EC 1.5.- KW - deoxyhypusine synthase KW - EC 1.5.1.- KW - Lysine KW - K3Z4F929H6 KW - Index Medicus KW - Mutagenesis, Site-Directed KW - Peptide Initiation Factors -- metabolism KW - Animals KW - Humans KW - Protein Processing, Post-Translational KW - Molecular Sequence Data KW - Mice KW - Amino Acid Sequence KW - Binding Sites KW - Saccharomyces cerevisiae -- genetics KW - Oxidoreductases Acting on CH-NH Group Donors -- metabolism KW - Lysine -- analogs & derivatives KW - Saccharomyces cerevisiae -- enzymology KW - Oxidoreductases Acting on CH-NH Group Donors -- chemistry KW - Lysine -- metabolism UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69588911?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Yeast+%28Chichester%2C+England%29&rft.atitle=Identification+of+lysine350+of+yeast+deoxyhypusine+synthase+as+the+site+of+enzyme+intermediate+formation.&rft.au=Wolff%2C+E+C%3BPark%2C+M+H&rft.aulast=Wolff&rft.aufirst=E&rft.date=1999-01-15&rft.volume=15&rft.issue=1&rft.spage=43&rft.isbn=&rft.btitle=&rft.title=Yeast+%28Chichester%2C+England%29&rft.issn=0749503X&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-06-29 N1 - Date created - 1999-06-29 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Conserved residues amino-terminal of cytoplasmic tyrosines contribute to the SHP-1-mediated inhibitory function of killer cell Ig-like receptors. AN - 69561708; 9916713 AB - The sequence I/VxYxxL, often referred to as an immunoreceptor tyrosine-based inhibition motif (ITIM), binds to the C-terminal Src homology 2 domain of the tyrosine phosphatase SHP-1. Conserved residues N-terminal of the tyrosine are not ordinarily found in other Src homology 2 domain binding motifs. The inhibitory forms of killer cell Ig-like receptors (KIR) contain two ITIMs. The role of each ITIM, and of the conserved residues upstream of the tyrosine, in the inhibition of NK cells was tested by vaccinia virus-mediated expression of mutant KIRs. Substitution of the tyrosine in the membrane-proximal ITIM abrogated the ability of KIR to block Ab-dependent cellular cytotoxicity, whereas mutation of the membrane-distal ITIM tyrosine had little effect. Substitution of the conserved hydrophobic amino acid that was located two residues N-terminal to the tyrosine weakened, but did not eliminate, the function of the receptor. In contrast, these substitutions drastically reduced the amount of SHP-1 immunoprecipitated with KIR, suggesting that weak interactions with SHP-1 may be sufficient for inhibition. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Burshtyn, D N AU - Lam, A S AU - Weston, M AU - Gupta, N AU - Warmerdam, P A AU - Long, E O AD - Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852-1727, USA. Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 897 EP - 902 VL - 162 IS - 2 SN - 0022-1767, 0022-1767 KW - Intracellular Signaling Peptides and Proteins KW - 0 KW - Peptide Fragments KW - Receptors, Immunologic KW - Receptors, KIR KW - Isoleucine KW - 04Y7590D77 KW - Tyrosine KW - 42HK56048U KW - PTPN11 protein, human KW - EC 3.1.3.48 KW - PTPN6 protein, human KW - Protein Tyrosine Phosphatase, Non-Receptor Type 11 KW - Protein Tyrosine Phosphatase, Non-Receptor Type 6 KW - Protein Tyrosine Phosphatases KW - Ptpn11 protein, mouse KW - Ptpn6 protein, mouse KW - SH2 Domain-Containing Protein Tyrosine Phosphatases KW - Valine KW - HG18B9YRS7 KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Humans KW - Amino Acid Sequence KW - Mice KW - Valine -- genetics KW - Killer Cells, Natural -- enzymology KW - Isoleucine -- genetics KW - Mutagenesis, Site-Directed KW - Mice, Inbred C57BL KW - Molecular Sequence Data KW - Killer Cells, Natural -- metabolism KW - Killer Cells, Natural -- immunology KW - Peptide Fragments -- genetics KW - Protein Tyrosine Phosphatases -- genetics KW - Protein Tyrosine Phosphatases -- metabolism KW - Receptors, Immunologic -- physiology KW - Protein Tyrosine Phosphatases -- physiology KW - Peptide Fragments -- immunology KW - Peptide Fragments -- physiology KW - Receptors, Immunologic -- genetics KW - src Homology Domains -- genetics KW - Conserved Sequence KW - Cytoplasm -- immunology KW - Cytoplasm -- metabolism KW - Tyrosine -- genetics KW - src Homology Domains -- immunology KW - Cytoplasm -- enzymology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69561708?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=Conserved+residues+amino-terminal+of+cytoplasmic+tyrosines+contribute+to+the+SHP-1-mediated+inhibitory+function+of+killer+cell+Ig-like+receptors.&rft.au=Burshtyn%2C+D+N%3BLam%2C+A+S%3BWeston%2C+M%3BGupta%2C+N%3BWarmerdam%2C+P+A%3BLong%2C+E+O&rft.aulast=Burshtyn&rft.aufirst=D&rft.date=1999-01-15&rft.volume=162&rft.issue=2&rft.spage=897&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-08 N1 - Date created - 1999-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy. AN - 69555221; 9916724 AB - A majority of the human tumor-associated Ags characterized to date are derived from nonmutated "self"-proteins. Little is currently understood about the nature of the self-reactive lymphocytes that recognize these Ags. We recently characterized two nonmutated tumor-associated Ags for the B16 murine melanoma: tyrosinase-related protein-2 (TRP-2) and the endogenous retroviral envelope protein, p15E. We previously reported that both TRP-2 and p15E reactive CTL could be detected in the spleens of naive animals after a single in vitro stimulation using 10(-5)-10(-6) M of the appropriate Kb-binding 9-amino acid epitope. In this report we show that the CTL found in naive animals are low avidity lymphocytes, that respond only to high concentrations of peptide in vitro. We demonstrate that titration of in vitro-stimulating peptide to limiting concentrations distinguishes qualitative differences in the lymphocyte reactivity to these two Ags between vaccinated and unvaccinated animals. We further demonstrate that in vitro expansion of CTL in either high or low concentrations of stimulating peptide generated CTL cultures with different avidities for the relevant epitopes. CTL expanded in low concentrations demonstrated higher avidity for peptide-pulsed targets and better tumor recognition, when compared to CTL generated in the presence of high concentrations of Ag. More importantly, high avidity CTL demonstrated superior in vivo antitumor activity. These results demonstrate that qualitative differences in the CTL that recognize these two self-Ags are critically important to their in vitro and in vivo anti-tumor efficacy. JF - Journal of immunology (Baltimore, Md. : 1950) AU - Zeh, H J AU - Perry-Lalley, D AU - Dudley, M E AU - Rosenberg, S A AU - Yang, J C AD - Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 989 EP - 994 VL - 162 IS - 2 SN - 0022-1767, 0022-1767 KW - Antigens, Neoplasm KW - 0 KW - Cancer Vaccines KW - Oligopeptides KW - Abridged Index Medicus KW - Index Medicus KW - Animals KW - Injections, Intravenous KW - Lung Neoplasms -- immunology KW - Lung Neoplasms -- secondary KW - Oligopeptides -- administration & dosage KW - Oligopeptides -- immunology KW - Lung Neoplasms -- therapy KW - Mice KW - Lymphocyte Activation KW - Cancer Vaccines -- immunology KW - Tumor Cells, Cultured KW - Cells, Cultured KW - Dose-Response Relationship, Immunologic KW - Oligopeptides -- therapeutic use KW - Mice, Inbred C57BL KW - Cytotoxicity Tests, Immunologic KW - Cell Line KW - Female KW - Cytotoxicity, Immunologic KW - Antigens, Neoplasm -- therapeutic use KW - Antigens, Neoplasm -- metabolism KW - T-Lymphocytes, Cytotoxic -- immunology KW - Antigens, Neoplasm -- immunology KW - T-Lymphocytes, Cytotoxic -- metabolism KW - Melanoma, Experimental -- therapy KW - Melanoma, Experimental -- immunology UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69555221?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.atitle=High+avidity+CTLs+for+two+self-antigens+demonstrate+superior+in+vitro+and+in+vivo+antitumor+efficacy.&rft.au=Zeh%2C+H+J%3BPerry-Lalley%2C+D%3BDudley%2C+M+E%3BRosenberg%2C+S+A%3BYang%2C+J+C&rft.aulast=Zeh&rft.aufirst=H&rft.date=1999-01-15&rft.volume=162&rft.issue=2&rft.spage=989&rft.isbn=&rft.btitle=&rft.title=Journal+of+immunology+%28Baltimore%2C+Md.+%3A+1950%29&rft.issn=00221767&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-02-08 N1 - Date created - 1999-02-08 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - Exploring the conformational properties of the sequence space between two proteins with different folds: an experimental study. AN - 69550003; 9878441 AB - We have examined the conformational properties of 27 polypeptides whose sequences are hybrids of two natural protein domains with 8 % sequence identity and different structures. One of the natural sequences (spectrin SH3 domain) was progressively mutated to get closer to the other sequence (protein G B1 domain), with the only constraint of maintaining the residues at the hydrophobic core. Only two of the mutants are folded, each of them having a large sequence identity with one of the two natural proteins. The rest of the mutants display a wide range of structural properties, but they lack a well-defined three-dimensional structure, a result that is not recognized by computational tools commonly used to evaluate the reliability of structural models. Interestingly, some of the mutants exhibit cooperative thermal denaturation curves and a signal in the near-ultraviolet circular dichroism spectra, both typical features of folded proteins. However, they do not have a well-dispersed nuclear magnetic resonance spectrum indicative of a defined tertiary structure. The results obtained here show that both the hydrophobic core residues and the surface residues are important in determining the structure of the proteins, and suggest that the appearance of a completely new fold from an existing one is unlikely to occur by evolution through a route of folded intermediate sequences. Copyright 1999 Academic Press. JF - Journal of molecular biology AU - Blanco, F J AU - Angrand, I AU - Serrano, L AD - European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg, 69117, Germany. blanco@speck.niddk.nih.gov Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 741 EP - 753 VL - 285 IS - 2 SN - 0022-2836, 0022-2836 KW - Bacterial Proteins KW - 0 KW - IgG Fc-binding protein, Streptococcus KW - Peptides KW - Spectrin KW - 12634-43-4 KW - Index Medicus KW - Molecular Sequence Data KW - Amino Acid Sequence KW - Mutagenesis KW - Protein Structure, Secondary KW - Magnetic Resonance Spectroscopy -- methods KW - Bacterial Proteins -- genetics KW - Bacterial Proteins -- chemistry KW - Protein Folding KW - Peptides -- chemistry KW - Spectrin -- genetics KW - Peptides -- genetics KW - Spectrin -- chemistry UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/69550003?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxline&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+molecular+biology&rft.atitle=Exploring+the+conformational+properties+of+the+sequence+space+between+two+proteins+with+different+folds%3A+an+experimental+study.&rft.au=Blanco%2C+F+J%3BAngrand%2C+I%3BSerrano%2C+L&rft.aulast=Blanco&rft.aufirst=F&rft.date=1999-01-15&rft.volume=285&rft.issue=2&rft.spage=741&rft.isbn=&rft.btitle=&rft.title=Journal+of+molecular+biology&rft.issn=00222836&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date completed - 1999-03-11 N1 - Date created - 1999-03-11 N1 - Date revised - 2017-01-13 N1 - Last updated - 2017-01-18 ER - TY - JOUR T1 - In Vitro Estrogenicity of the Catechol Metabolites of Selected Polychlorinated Biphenyls AN - 18411133; 5405618 AB - A considerable body of work has demonstrated that phenolic polychlorinated biphenyl (PCB) metabolites, structural analogues to estradiol, bind to the soluble estrogen receptor (ER) and that hydroxy PCB-ER complexes will translocate into the nucleus and bind to ER response elements in cultured cells. Although catechol estrogens exhibit weak estrogenic activity, the catechol PCB metabolites which are structurally similar to these ER agonists have gone untested for potential estrogenicity. In the present work we have assessed the estrogenicity of this second group of PCB metabolites, the catechols. The test compounds used in the present study were chosen to elucidate the effects of chlorine and catechol position on in vitro estrogenicity. Cultured HeLa cells, transfected with the estrogen reporter gene ERET81CAT and mouse ER cDNA, were incubated with PCB catechols. The cells were harvested at 28 h posttransfection and assayed for chloramphenicol acetyl transferase (CAT) activity. The responses elicited by the PCB catechols tested fell within the range of effect measured for the catechol estrogens and phenolic PCBs, and were within the range previously reported for other "environmental estrogens" such as nonylphenol and o,p'-DDT. Maximal measured responses were achieved at concentrations approximately two to three orders of magnitude higher than that of 17- beta -estradiol, indicating that PCB catechols have estrogenic activity in vitro.The extent of chlorination and the position of the catechol (3,4 vs 2,3 substitution) were important in determining estrogenicity in the compounds tested. The 2,3-catechol showed no detectable activity in this system, while activity of the 3,4-catechols increased with the degree of chlorination. The observed estrogenicity of PCB catechols suggests that further oxidative metabolism of estrogenic PCB phenolic metabolites would not necessarily result in lowering the total estrogenic burden of a PCB-exposed organism. The present results imply that if estrogenic activity is assigned to an individual phenol, the potential contribution of its catechol metabolites to the total estrogenic burden should also be taken into consideration. JF - Toxicology and Applied Pharmacology AU - Garner, CE AU - Jefferson, W N AU - Burka, L T AU - Matthews, H B AU - Newbold, R R AD - Laboratory of Pharmacology and Chemistry, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709 Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 188 EP - 197 PB - Academic Press, Inc., 525 B St. Ste. 1900 San Diego CA 92101-4495 USA, [mailto:apsubs@acad.com] VL - 154 IS - 2 SN - 0041-008X, 0041-008X KW - catechols KW - estrogenic activity KW - metabolites KW - Toxicology Abstracts KW - X 24190:Polycyclic hydrocarbons UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/18411133?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Atoxicologyabstracts&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Toxicology+and+Applied+Pharmacology&rft.atitle=In+Vitro+Estrogenicity+of+the+Catechol+Metabolites+of+Selected+Polychlorinated+Biphenyls&rft.au=Garner%2C+CE%3BJefferson%2C+W+N%3BBurka%2C+L+T%3BMatthews%2C+H+B%3BNewbold%2C+R+R&rft.aulast=Garner&rft.aufirst=CE&rft.date=1999-01-15&rft.volume=154&rft.issue=2&rft.spage=188&rft.isbn=&rft.btitle=&rft.title=Toxicology+and+Applied+Pharmacology&rft.issn=0041008X&rft_id=info:doi/10.1006%2Ftaap.1998.8560 LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 DO - http://dx.doi.org/10.1006/taap.1998.8560 ER - TY - JOUR T1 - Use of a Sandwich Enzyme-linked Immunosorbent Assay Strategy to Study Mechanisms of G Protein-coupled Receptor Assembly AN - 17165033; 4455772 AB - All G protein-coupled receptors are predicted to consist of a bundle of seven transmembrane helices (I-VII) that are connected by various extracellular and intracellular loops. At present, little is known about the molecular interactions that are critical for the proper assembly of the transmembrane receptor core. To address this issue, we took advantage of the ability of coexpressed N- and C-terminal m3 muscarinic receptor fragments to form functional receptor complexes. As a model system, we used two polypeptides, referred to as m3-trunk and m3-tail, that were generated by "splitting" the m3 muscarinic receptor within the third intracellular loop. We initially demonstrated, by employing a sandwich enzyme- linked immunosorbent assay strategy, that the two receptor fragments directly associate with each other when coexpressed in COS-7 cells. Additional studies with N- and C-terminal fragments derived from other G protein- coupled receptors showed that fragment association was highly receptor-specific. In subsequent experiments, the sandwich enzyme-linked immunosorbent assay system was used to identify amino acids that are required for proper fragment (receptor) assembly. Point mutations were introduced into m3-trunk or m3-tail, and the ability of these mutations to interfere with efficient fragment assembly was examined. These studies showed that three highly conserved proline residues (located in transmembrane helices V, VI, and VII) are essential for proper fragment association (receptor assembly). Interestingly, incubation with classical muscarinic agonists and antagonists or allosteric ligands led to significant increases in the efficiency of fragment association (particularly upon substitution of the conserved proline residues) indicating that all of these ligands can act as "anchors" between the m3-trunk and m3-tail fragments. The approach described here should be generally applicable to gain deeper insight into the molecular mechanisms governing G protein-coupled receptor structure and assembly. JF - Journal of Biological Chemistry AU - Jakubik, J AU - Wess, J AD - Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892 USA Y1 - 1999/01/15/ PY - 1999 DA - 1999 Jan 15 SP - 1349 EP - 1358 VL - 274 IS - 3 SN - 0021-9258, 0021-9258 KW - COS-7 cells KW - double prime G protein-coupled receptors KW - guanine nucleotide-binding protein KW - muscarinic receptors KW - Biotechnology and Bioengineering Abstracts; Medical and Pharmaceutical Biotechnology Abstracts KW - Enzyme-linked immunosorbent assay KW - W3 33240:Immunology KW - W 30965:Miscellaneous, Reviews UR - http://libproxy.lib.unc.edu/login?url=http://search.proquest.com/docview/17165033?accountid=14244 L2 - http://vb3lk7eb4t.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&rfr_id=info:sid/ProQ%3Abiotechresearch&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.jtitle=Journal+of+Biological+Chemistry&rft.atitle=Use+of+a+Sandwich+Enzyme-linked+Immunosorbent+Assay+Strategy+to+Study+Mechanisms+of+G+Protein-coupled+Receptor+Assembly&rft.au=Jakubik%2C+J%3BWess%2C+J&rft.aulast=Jakubik&rft.aufirst=J&rft.date=1999-01-15&rft.volume=274&rft.issue=3&rft.spage=1349&rft.isbn=&rft.btitle=&rft.title=Journal+of+Biological+Chemistry&rft.issn=00219258&rft_id=info:doi/ LA - English DB - ProQuest Environmental Science Collection N1 - Date revised - 2006-11-01 N1 - Last updated - 2011-12-13 N1 - SubjectsTermNotLitGenreText - Enzyme-linked immunosorbent assay ER -